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4: Introduction to the Human Body - Biology

4: Introduction to the Human Body - Biology


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This chapter outlines the organization of the human body and describes human cells, tissues, organs, organ systems, and body cavities. It also explains how organ systems interact and how feedback mechanisms maintain homeostasis in the body.

  • 4.1: Case Study- Getting to Know Your Body
    Looking at the photo of a football game above, you can see why it is so important that the players wear helmets. Football often involves forceful impact to the head as players tackle each other. This can cause damage to the brain - either temporarily as in the case of a concussion, or long-term and more severe types of damage. Helmets are critical to reduce the incidence of traumatic brain injuries (TBIs), but they do not fully prevent them.
  • 4.2: Organization of the Body
    This six-legged robot was created for research, but it looks like it might be fun to play with. It's obviously a complex machine. Think about some other, more familiar machines, such as power drills, washing machines, and lawn mowers. Each machine consists of many parts, and each part does a specific job, yet all the parts work together to perform certain functions.
  • 4.3: Human Cells and Tissues
    This photo looks like a close-up of an old-fashioned dust mop, and the object it shows has a somewhat similar function. However, the object is greatly enlarged in the photo. Can you guess what it is? The answer may surprise you.
  • 4.4: Human Organs and Organ Systems
    An organ is a collection of tissues joined in a structural unit to serve a common function. Organs exist in most multicellular organisms, including not only humans and other animals but also plants. In single-celled organisms such as bacteria, the functional equivalent of an organ is an organelle.
  • 4.5: Human Body Cavities
    The human body, like that of many other multicellular organisms, is divided into a number of body cavities. A body cavity is a fluid-filled space inside the body that holds and protects internal organs. Human body cavities are separated by membranes and other structures. The two largest human body cavities are the ventral cavity and dorsal cavity. These two body cavities are subdivided into smaller body cavities.
  • 4.6: Interaction of Organ Systems
    Communication among organ systems is vital if they are to work together as a team. They must be able to respond to each other and change their responses as needed to keep the body in balance. Communication among organ systems is controlled mainly by the autonomic nervous system and the endocrine system.
  • 4.7: Homeostasis and Feedback
    Homeostasis is the condition in which a system such as the human body is maintained in a more-or-less steady state. It is the job of cells, tissues, organs, and organ systems throughout the body to maintain many different variables within narrow ranges that are compatible with life. Keeping a stable internal environment requires continually monitoring the internal environment and constantly making adjustments to keep things in balance.
  • 4.8: Case Study - Pressure Conclusion and Chapter Summary
    As you learned in this chapter, the human body consists of many complex systems that normally work together efficiently like a well-oiled machine to carry out life's functions.

Introduction to Human Biology 101

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Carbohydrates

Carbohydrates are macromolecules with which most consumers are somewhat familiar. To lose weight, some individuals adhere to “low-carb” diets. Athletes, in contrast, often “carb-load” before important competitions to ensure that they have sufficient energy to compete at a high level. Carbohydrates are, in fact, an essential part of our diet grains, fruits, and vegetables are all natural sources of carbohydrates. Carbohydrates provide energy to the body, particularly through glucose, a simple sugar. Carbohydrates also have other important functions in humans, animals, and plants.

Carbohydrates can be represented by the formula (CH2O)n, where n is the number of carbon atoms in the molecule. In other words, the ratio of carbon to hydrogen to oxygen is 1:2:1 in carbohydrate molecules. Carbohydrates are classified into three subtypes: monosaccharides, disaccharides, and polysaccharides.

Monosaccharides (mono- = “one” sacchar- = “sweet”) are simple sugars, the most common of which is glucose. In monosaccharides, the number of carbon atoms usually ranges from three to six. Most monosaccharide names end with the suffix -ose. Depending on the number of carbon atoms in the sugar, they may be known as trioses (three carbon atoms), pentoses (five carbon atoms), and hexoses (six carbon atoms).

Monosaccharides may exist as a linear chain or as ring-shaped molecules in aqueous solutions, they are usually found in the ring form.

The chemical formula for glucose is C6H12O6. In most living species, glucose is an important source of energy. During cellular respiration, energy is released from glucose, and that energy is used to help make adenosine triphosphate (ATP). Plants synthesize glucose using carbon dioxide and water by the process of photosynthesis, and the glucose, in turn, is used for the energy requirements of the plant. The excess synthesized glucose is often stored as starch that is broken down by other organisms that feed on plants.

Galactose (part of lactose, or milk sugar) and fructose (found in fruit) are other common monosaccharides. Although glucose, galactose, and fructose all have the same chemical formula (C6H12O6), they differ structurally and chemically (and are known as isomers) because of differing arrangements of atoms in the carbon chain (Figure 3).

Figure 3. Glucose, galactose, and fructose are isomeric monosaccharides, meaning that they have the same chemical formula but slightly different structures.

Disaccharides (di- = “two”) form when two monosaccharides undergo a dehydration reaction (a reaction in which the removal of a water molecule occurs). During this process, the hydroxyl group (–OH) of one monosaccharide combines with a hydrogen atom of another monosaccharide, releasing a molecule of water (H2O) and forming a covalent bond between atoms in the two sugar molecules.

Common disaccharides include lactose, maltose, and sucrose. Lactose is a disaccharide consisting of the monomers glucose and galactose. It is found naturally in milk. Maltose, or malt sugar, is a disaccharide formed from a dehydration reaction between two glucose molecules. The most common disaccharide is sucrose, or table sugar, which is composed of the monomers glucose and fructose.

A long chain of monosaccharides linked by covalent bonds is known as a polysaccharide (poly- = “many”). The chain may be branched or unbranched, and it may contain different types of monosaccharides. Polysaccharides may be very large molecules. Starch, glycogen, cellulose, and chitin are examples of polysaccharides.

Starch is the stored form of sugars in plants and is made up of amylose and amylopectin (both polymers of glucose). Plants are able to synthesize glucose, and the excess glucose is stored as starch in different plant parts, including roots and seeds. The starch that is consumed by animals is broken down into smaller molecules, such as glucose. The cells can then absorb the glucose.

Glycogen is the storage form of glucose in humans and other vertebrates, and is made up of monomers of glucose. Glycogen is the animal equivalent of starch and is a highly branched molecule usually stored in liver and muscle cells. Whenever glucose levels decrease, glycogen is broken down to release glucose.

Cellulose is one of the most abundant natural biopolymers. The cell walls of plants are mostly made of cellulose, which provides structural support to the cell. Wood and paper are mostly cellulosic in nature. Cellulose is made up of glucose monomers that are linked by bonds between particular carbon atoms in the glucose molecule.

Every other glucose monomer in cellulose is flipped over and packed tightly as extended long chains. This gives cellulose its rigidity and high tensile strength—which is so important to plant cells. Cellulose passing through our digestive system is called dietary fiber. While the glucose-glucose bonds in cellulose cannot be broken down by human digestive enzymes, herbivores such as cows, buffalos, and horses are able to digest grass that is rich in cellulose and use it as a food source. In these animals, certain species of bacteria reside in the rumen (part of the digestive system of herbivores) and secrete the enzyme cellulase. The appendix also contains bacteria that break down cellulose, giving it an important role in the digestive systems of ruminants. Cellulases can break down cellulose into glucose monomers that can be used as an energy source by the animal.

Carbohydrates serve other functions in different animals. Arthropods, such as insects, spiders, and crabs, have an outer skeleton, called the exoskeleton, which protects their internal body parts. This exoskeleton is made of the biological macromolecule chitin, which is a nitrogenous carbohydrate. It is made of repeating units of a modified sugar containing nitrogen.

Thus, through differences in molecular structure, carbohydrates are able to serve the very different functions of energy storage (starch and glycogen) and structural support and protection (cellulose and chitin) (Figure 4).

Figure 4. Although their structures and functions differ, all polysaccharide carbohydrates are made up of monosaccharides and have the chemical formula (CH2O)n.

Registered Dietitian

Obesity is a worldwide health concern, and many diseases, such as diabetes and heart disease, are becoming more prevalent because of obesity. This is one of the reasons why registered dietitians are increasingly sought after for advice. Registered dietitians help plan food and nutrition programs for individuals in various settings. They often work with patients in health-care facilities, designing nutrition plans to prevent and treat diseases. For example, dietitians may teach a patient with diabetes how to manage blood-sugar levels by eating the correct types and amounts of carbohydrates. Dietitians may also work in nursing homes, schools, and private practices.

To become a registered dietitian, one needs to earn at least a bachelor’s degree in dietetics, nutrition, food technology, or a related field. In addition, registered dietitians must complete a supervised internship program and pass a national exam. Those who pursue careers in dietetics take courses in nutrition, chemistry, biochemistry, biology, microbiology, and human physiology. Dietitians must become experts in the chemistry and functions of food (proteins, carbohydrates, and fats).


Paleoanthropology

Paleoanthropology is the scientific study of human evolution. Paleoanthropology is a subfield of anthropology, the study of human culture, society, and biology. The field involves an understanding of the similarities and differences between humans and other species in their genes, body form, physiology, and behavior. Paleoanthropologists search for the roots of human physical traits and behavior. They seek to discover how evolution has shaped the potentials, tendencies, and limitations of all people. For many people, paleoanthropology is an exciting scientific field because it investigates the origin, over millions of years, of the universal and defining traits of our species. However, some people find the concept of human evolution troubling because it can seem not to fit with religious and other traditional beliefs about how people, other living things, and the world came to be. Nevertheless, many people have come to reconcile their beliefs with the scientific evidence.

Early human fossils and archeological remains offer the most important clues about this ancient past. These remains include bones, tools and any other evidence (such as footprints, evidence of hearths, or butchery marks on animal bones) left by earlier people. Usually, the remains were buried and preserved naturally. They are then found either on the surface (exposed by rain, rivers, and wind erosion) or by digging in the ground. By studying fossilized bones, scientists learn about the physical appearance of earlier humans and how it changed. Bone size, shape, and markings left by muscles tell us how those predecessors moved around, held tools, and how the size of their brains changed over a long time. Archeological evidence refers to the things earlier people made and the places where scientists find them. By studying this type of evidence, archeologists can understand how early humans made and used tools and lived in their environments.


Factors shaping the GI microbiota

The microbiota composition is subject to shaping by host and environmental selective pressures. To protect from injury and maintain homeostasis, the GI tract limits exposure of the host immune system to the microbiota by recruitment of a multifactorial and dynamic intestinal barrier. The barrier comprises several integrated components including physical (the epithelial and mucus layers), biochemical (enzymes and antimicrobial proteins) and immunological (IgA and epithelia-associated immune cells) factors [51]. An individual microbe's longevity is determined by whether it is contributing to the range of essential functions on which host fitness relies. It is proposed that organisms who do not contribute beneficial functions are controlled by, and may occasionally be purged during, for example, transferral of the microbiota to a new host [52,53].

Gut microbes must be adapted to a certain type of lifestyle due to the relatively fewer number of biochemical niches available in the gut, compared with other microbial-rich environments. In the gut, energy can generally be derived through processes such as fermentation and sulphate reduction of dietary and host carbohydrates. The organisms that can survive in the gut are therefore limited by their phenotypic traits [52].

Current research suggests that diet exerts a large effect on the gut microbiota [40]. Meta-transcriptomic studies revealed that the ileal microbiota is driven by the capacity of the microbial members to metabolise simple sugars, reflecting adaptation of the microbiota to the nutrient availability in the small intestine [54]. Shaping of the colonic microbiota is subject to the availability of microbiota-accessible carbohydrates (MACs) that are found in dietary fibre. Extreme 𠆊nimal-based’ or ‘plant-based’ diets result in wide-ranging alterations of the gut microbiota in humans [55]. The influence of fibre was demonstrated in a crossover study showing that otherwise matched diets high in resistant starch or in non-starch polysaccharide fibre (wheat bran) resulted in the strong and reproducible enrichment of different bacterial species in the human gut [56]. Feeding methods can also affect the abundance of some bacterial groups in the gut microbiota of infants. For example, fucosylated oligosaccharides present in human milk can be utilised by Bifidobacterium longum and several species of Bacteroides allowing them to outcompete other bacteria such as E. coli and Clostridium perfringens [57,58]. Whilst the abundance of Bifidobacterium spp. in breast-fed infant microbiota is typically high [57], this is reduced in formula-fed infants [59]. Furthermore, formula-fed infant microbiota has an increased diversity and altered levels of other groups such as E. coli, Clostridium difficile, Bacteroides fragilis and lactobacilli [59�]. The microbiota of undernourished infants is immature, dysbiotic and contains greater numbers of enteropathogens, such as Enterobacteriaceae [62]. Infants from rural Africa, with a diet dominated by starch, fibre and plant polysaccharides, harbour a microbiota that is abundant in the Actinobacteria (10.1%) and Bacteroidetes (57.7%) phyla [63]. In contrast, in European children, whose diet is rich in sugar, starch and animal protein, the abundance of these groups is reduced to just 6.7 and 22.4% [63]. Some SCFA producers, such as Prevotella, were exclusive to the microbiota of African children [63]. This trend was also apparent in healthy individuals consuming high amounts of carbohydrates and simple sugars [64]. A decreased SCFA output is also evident in individuals consuming a low MAC diet, a notable effect since SCFAs play an important role in host health via, for example, anti-inflammatory mechanisms [65]. The abundance of MACs is substantially reduced in the Western diet. Administration of a low MAC diet to mice results in a reduction in microbial diversity [66]. Restoration of diversity requires administration of MACs in combination with the bacterial taxa that were missing [66]. Recent studies using gnotobiotic mice showed that certain microbial species can be used to restore growth impairments transmitted by microbiota from malnourished children, raising the possibility of using these species as a therapeutic intervention to counteract the negative effects of undernutrition [67�].

Intestinal mucus also provides a source of carbohydrates to the gut microbiota [70,71]. The intestinal mucus layers are built around the large highly glycosylated gel-forming mucin MUC2 (Muc2 in mouse) secreted by goblet cells [72]. The glycan structures present in mucins are diverse and complex and based on four core mucin-type O-glycans containing N-acetylgalactosamine, galactose and N-acetylglucosamine. These core structures are further elongated and frequently terminated by fucose and sialic acid sugar residues. Collectively, O-glycans account for up to 80% of the total molecular mass of Muc2/MUC2 [73]. Mucus is present throughout the GI tract and is thickest in the colon where it is crucial in mediating the host–microbiota relationship [74]. Normalisation of host intestinal mucus layers requires long-term microbial colonisation [75]. Colonic mucus is divided into two layers consisting of a dense and impermeable inner layer and a loose outer coating which is penetrable by bacteria [74]. Whilst the inner layer is virtually sterile, in the outer layer, the mucin proteins, which are decorated by a rich and diverse repertoire of O-glycans, provide an energy source and preferential binding sites for commensal bacteria [73,76,77]. The arrangement of the outer mucus layer provides a unique niche in which bacterial species display different patterns of proliferation and utilisation of resources compared with their counterparts in the lumen [45]. The type of mucin O-glycosylation is dependent on the glycosyltransferases expressed and where in the Golgi apparatus they are located [71], alterations of which affect the microbiota composition. For example, the presence (secretor) or absence (non-secretor) of H and ABO antigens in GI mucosa, determined by the FUT2 genotype (a gene expressing an 㬑,2-fucosyltransferase), affects the abundance of many bacterial groups [78]. Mucus and mucin glycosylation are therefore key in shaping the microbiota and allow for the selection of the most optimal microbial species to mediate host health [79�]. A depletion of MACs from the diet of mice can result in thinner mucus in the distal colon, increased proximity of microbes to the epithelium and heightened expression of the inflammatory marker REGIIIβ [82]. The erosion of the colonic mucus barrier under dietary fibre deficiency is associated with a switch of the gut microbiota towards the utilisation of secreted mucins as a nutrient source [83]. On the other hand, administration of a mucin degrader, A. muciniphila, to mice prevents the development of high-fat diet-induced obesity and ameliorates metabolic endotoxemia-induced inflammation through restoration of the gut barrier [84,85]. Some of these effects are the result of increased mucin secretion and intestinal tight-junction proteins, which highlight the dynamic role played by mucin degraders in their interaction with the host. The protective role of A. muciniphila could be recapitulated using A. muciniphila purified membrane protein or the pasteurised bacterium [86]. Recently, A. muciniphila supplementation was shown to significantly alleviate body weight gain and reduce fat mass in chow diet-fed mice by relieving metabolic inflammation [87]. These studies suggest the potential of A. muciniphila as a therapeutic option to target human obesity and associated disorders.

The capacity of gut bacteria to utilise dietary or mucin glycans is dictated by the repertoire of glycoside hydrolases (GHs) and polysaccharide lyases (PLs) encoded by their genomes [70]. Some species act as generalists able to degrade a wide range of polysaccharides, whilst others are specialists targeting specific glycans [88]. Bacteroidetes encode many more glycan-cleaving enzymes (137.1 GH and PL genes per genome) than Firmicutes members (39.6 GH and PL genes per genome) [89]. The Bacteroides thetaiotaomicron genome contains 260 GHs, in comparison with the 97 hydrolases encoded by humans [90]. The GH13 family, which contains enzymes involved in the breakdown of starch, is the most represented family in the gut microbiota [89]. Recently, the detailed biochemical and structural characterisation of the extensive degrading apparatus of prominent gut species such as B. thetaiotaomicron or Bacteroides ovatus revealed that the recognition and breakdown of complex carbohydrates, such as xylan, mannan, xyloglucan or starch, by the human gut microbiota is significantly more complex than previously suggested [91�]. Although less studied, members of Firmicutes also show some unique and complex features such as the recent discovery of amylosomes in the resistant starch-utilising bacterium Ruminococcus bromii [97].

Diversification of the microbial population can occur through, for example, mutation or lateral gene transfer [98,99]. The introduction of new bacterial functions promotes niche variation, creating a positive feedback loop in which more diversification can occur [100,101]. Co-operation between gut microbes also allows colonisation by a more diverse set of organisms, shaping the gut microbiota community. Microbial cross-feeding is one mechanism proposed to mediate this effect. Some carbohydrate fermentation products, including lactate, succinate and 1,2-propanediol, do not usually accumulate to high levels in the human colon of healthy adults, as they can serve as substrates for other bacteria, including propionate and butyrate producers [102]. For example, acetate produced by fermentation of resistant starch by R. bromii [103] or lactate produced by lactic acid bacteria such as lactobacilli and bifidobacteria provides substrate for other microbiota members such as Eubacterium hallii and Anaerostipes caccae which convert it into butyrate [104,105]. Recently, B. ovatus has been demonstrated to perform extracellular digestion of inulin at its own cost, but at an advantage to other species which provide reciprocal benefits [106]. Such co-operation is particularly apparent in the outer mucus layer where mucin-degrading bacteria provide mono- or oligosaccharides to bacteria without specialised mucolytic capability [45]. For example, the capacity of cleaving sialic acid off mucins is restricted to bacterial species encoding GH33 sialidases. Many bacteria, including pathogens such as Salmonella Typhimurium or C. difficile, lack a sialidase but harbour a ‘nan cluster’ dedicated to sialic acid metabolism, and thus rely on other members of the gut microbiota to provide them with this source of carbon [107]. Intramolecular trans-sialidase is a new class of sialidases recently identified in Ruminococcus gnavus strains that may play a role in the adaptation of gut commensal bacteria to the mucosal niche [70,108,109]. This activity may provide such bacteria with a competitive nutritional advantage over other species within the gut mucosal environment, specifically in inflammatory bowel diseases, which is rich in short, sialylated mucin glycans [70,110].

The availability of sulphated compounds in the colon, either of inorganic (e.g. sulphates and sulphites) or organic (e.g. dietary amino acids and host mucins) origin, can influence specific groups of bacteria such as sulphate-reducing bacteria, which are residents of the gut microbiota that have been implicated in the aetiology of intestinal disorders such as IBD, IBS or colorectal cancer [111].

The distribution of bile acids in the small and large intestine can also affect the bacterial community dynamics in the gut as thoroughly reviewed [112,113]. Primary bile acids, such as taurocholate, can provide homing signals to gut bacteria and promote germination of spores, and may also facilitate recovery of microbiota after dysbiosis induced by antibiotics or toxins [114]. Furthermore, reduced bile acid concentration in the gut may play an important role in allowing pro-inflammatory microbial taxa to expand [115]. These studies highlight the role of bile acids in shaping the GI microbiota.

The microbiota can also be shaped by the host immune system. This effect is mostly limited to stratification and compartmentalisation of bacteria to avoid opportunistic invasion of host tissue, whilst species-specific effects are less probable due to the high amount of functional redundancy within the microbiota [52,116�]. Both host-derived and administered antimicrobials play a key role in shaping the gut microbiota. In the GI tract, Paneth cells produce antimicrobials such as angiogenin 4, α-defensins, cathelicidins, collectins, histatins, lipopolysaccharide (LPS)-binding protein, lysozymes, secretory phospholipase A2 and lectins such as REGIIIα/γ [120]. These proteins are localised in the mucus layer and are virtually absent from the lumen, probably either due to poor diffusion through mucus or luminal degradation [51,121]. Many secreted antimicrobial proteins (AMPs) kill bacteria through direct interaction with, and disruption of the bacterial cell wall or inner membrane via enzymatic attack [51]. Reduced mucosal α-defensin expression has been demonstrated in patients with ileal Crohn's disease (CD), highlighting the importance of these proteins [122,123]. Secretory IgA (SIgA), another component of the immune system, co-localises with gut bacteria in the outer mucus layer and assists in limiting the exposure of the epithelial cell surface to bacteria [120,124]. SIgA is proposed to mediate bacterial biofilm formation via binding to SIgA receptors on bacteria [125]. The expression of SIgA receptors by bacteria is reduced in IgA-deficient individuals [126]. Dysbiosis of the microbiota, in particular an over-representation of segmented filamentous bacteria (SFB), occurs in mice deficient in IgA, an effect that may be particularly damaging to the host due to the ability of SFB to strongly adhere to the epithelium and activate the immune system [127].

Several environmental factors have been implicated in shaping the microbiota including geographical location, surgery, smoking, depression and living arrangements (urban or rural) [24,128�]. Xenobiotics, such as antibiotics but not host-targeted drugs, shape the physiology and gene expression of the active human gut microbiome [131]. Antibiotic treatment dramatically disrupts both short- and long-term microbial balance, including decreases in the richness and diversity of the community. Clindamycin [132], clarithromycin and metronidazole [47], and ciproflaxin [33] have all been demonstrated to affect the microbiota structure for varying lengths of time. The exact effects and the time for recovery of the microbiota following antibiotic administration appear to be individual-dependent, a likely effect of the inter-individual variation in the microbiota prior to treatment [33,47,132]. An explorative study in humans showed that the administration of β-lactam intravenous therapy consisting of ampicillin, sulbactam and cefazolin affects both the microbial ecology and the production of key metabolites, such as acetyl phosphate and acetyl-CoA, that are involved in major cellular functions [133]. Recent investigations in mice demonstrated that microbiota depletion by antibiotics affected secondary bile acid and serotonin metabolism in the colon, resulting in delayed GI motility [134]. Antibiotic-treated mice are also more susceptible to pathogenic infection by antibiotic-associated pathogens, S. Typhimurium and C. difficile, due to an alteration in mucosal carbohydrate availability favouring their expansion into the gut [135]. A better understanding of the mechanisms leading to the antibiotic-induced blooms of bacteria and the biochemical activities and metabolites affected will help develop complementary and/or alternative strategies required for maintaining human health.


Contents

The key aspects of human biology are those ways in which humans are substantially different from other mammals. [5]

Humans have a very large brain in a head that is very large for the size of the animal. This large brain has enabled a range of unique attributes including the development of complex languages and the ability to make and use a complex range of tools. [6] [7]

The upright stance and bipedal locomotion is not unique to humans but humans are the only species to rely almost exclusively on this mode of locomotion. [8] This has resulted in significant changes in the structure of the skeleton including the articulation of the pelvis and the femur and in the articulation of the head.

In comparison with most other mammals, humans are very long lived [9] with an average age at death in the developed world of over 80. [10] Humans also have the longest childhood of any mammal with sexual maturity taking 12 to 16 years on average to be completed.

Humans lack fur. Although there is a residual covering of fine hair, which may be more developed in some men, and localised hair covering on the head, axillary and pubic regions, in terms of protection from cold, humans are almost naked. The reason for this development is still much debated.

The human eye can see objects in colour but is not well adapted to low light conditions. The sense of smell and of taste are present but are relatively inferior to a wide range of other mammals. Human hearing is efficient but lacks the acuity of some other mammals. Similarly human sense of touch is well developed especially in the hands where dextrous tasks are performed but the sensitivity is still significantly less than in other animals, particularly those equipped with sensory bristles such as cats.

Human biology tries to understand and promotes research on humans as living beings as a scientific discipline. It makes use of various scientific methods, such as experimentss and observations, to detail the biochemical and biophysical foundations of human life describe and formulate the underlying processes using models. As a basic science, it provides the knowledge base for medicine. A number of sub-disciplines include anatomy, cytology, histology and morphology.

The capabilities of the human brain and the human dexterity in making and using tools, has enabled humans to understand their own biology through scientific experiment, including dissection , autopsy, prophylactic medicine which has, in turn, enable humans to extend their life-span by understanding and mitigating the effects of diseases.

Understanding human biology has enabled and fostered a wider understanding of mammalian biology and by extension, the biology of all living organisms.

Human nutrition is typical of mammalian omnivorous nutrition requiring a balanced input of carbohydrates, fats, proteins, vitamins and minerals. However the human diet has a few very specific requirements. These include two specific amino acids, alpha-linolenic acid and linoleic acid without which life is not sustainable in the medium to long term. All other fatty acids can be synthesised from dietary fats. Similarly human life requires a range of vitamins to be present in food and if these are missing or are supplied at unacceptable low levels, metabolic disorders result which can end in death. The human metabolism is similar to most other mammals except for the need to have an intake of Vitamin C to prevent scurvy and other deficiency diseases. Unusually amongst the mammals, human can synthesize Vitamin D3 using natural UV light from the sun on the skin. This capability may be widespread in the mammalian world but few other mammals share the almost naked skin of humans. The darker the human's skin, the less it can manufacture Vitamin D3.

Human biology also encompasses all those organisms that live on or in the human body. Such organisms range from parasitic insects such as fleas and ticks, parasitic helminths such as liver flukes through to bacterial and viral pathogens. Many of the organisms associated with human biology are the specialised biome in the large intestine and the biotic flora of the skin and pharyngeal and nasal region. Many of these biotic assemblages help protect humans from harm and assist in digestion, and are now known to have complex effects on mood, and well-being.

Humans in all civilizations are social animals and use their language skills and tool making skills to communicate.

These communication skills enable civilizations to grow and allow for the production of art, literature and music, and for the development of technology. All of these are wholly dependent on the human biological specialisms.

The deployment of these skills has allowed the human race to dominate the terrestrial biome [11] to the detriment of most of the other species.


Water Metabolism in Human Body | Biology

In this article we will discuss about:- 1. Introduction to Water Metabolism 2. Distribution of Water in the Body 3. Water Content in Various Tissues 4. Functions of Water 5. Water Balance.

Introduction to Water Metabolism:

Of the three factors, water, salts and food, water is the most important. If we remember that life evolved first in an aquatic medium, there will be nothing to be astonished that water is the most essential substance for life. Deprivation of water will kill a subject much earlier than deprivation of salt or food. With water starvation death takes place in the shortest possible time (in about one week), when only 20% of the total body weight is lost.

Our former idea about the chemical constitution of water, having the formula H2O with a molecular weight 18, is fast changing and is probably no more tenable now. By studying the various properties of water, modern chemistry suggests that water is actually a polymer of H2O.

Critical temperature of water is 365°C. Boiling water is (H2O)3, ice is (H2O)4 and ordinary water is a mixture of the two. Experiments with heavy water (D2O) have clarified many aspects of water metabolism.

Distribution of Water in the Body:

Total water content is 60% to 70% of the adult body weight, i.e., 45—49 litres, females having somewhat lower values than males. Accumulated evidences suggest that using of body weight as a parameter of reference body water content is inversely related to the adiposity of the organism.

Thus increase of fatty tissue in the body will automatically result in a reciprocal decrease in total water content when expressed in terms of percent, body weight. Behnke, to minimise the errors in the concept of total body water, introduced the term lean body mass which is made up of functional tissue, containing only essential fat.

The total body water calculated on a fat free basis, according to the concept of lean body mass, on a large number of animals, e.g., rat, guinea-pig, cat, dog, monkeys, etc., averaged 73.2% range being 70—76%. This measurement is applicable only to normal adults. In very young, and in those having other abnormalities, deviations are to be expected.

The total body water is distributed throughout two main compartments:

(1) Intracellular, approximately 50% of the body weight (i.e., 39 litres), and

(2) Extra­cellular —20% of the body weight, i.e., 14 litres, of which 3 litres in plasma and 11 litres in interstitial fluid and lymph.

Recent investigations indicate that al­though the concept of a single intracellular water component is still useful, the extra­cellular component is more heterogeneous and is subdivided into four subcompo­nents:

1. Blood plasma (4.5% body water).

2. Interstitial fluid and lymph (8%).

3. Dense connective tissue, cartilage, bones (6%).

4. Transcellular fluids (1.5%), such as aqueous and vitreous humour, cerebro­spinal fluid, endolymph, perilymph, etc.

A man weighing 11 stones (70 kg) con­tains about 47 litres of water in the body. Of this, 20 litres (about half) are in the muscles and 10 litres (about one-fifth) in the skin. Blood contains about one-fourteenth part of the total body water. In young animals and in very active tissues, the water content is much higher. A baby contains water much over 70% of its body weight. Water content is maximum in the foetus and diminishes with age.

Water Content in Various Tissues:

The percentage of water in various tissues are as follows- skin, 20% muscles, 75—80% blood, 76% plasma, 92% connective tissues, 60% corpuscles, 60% (total amount of water in blood is 4—5 litres) nervous tissue -grey matter, 85% (more than in blood, yet it is solid) white matter, 70% adipose tissue, 20% dentine, 10% (least and therefore hardest) bones (without marrow), 25% cerebrospinal fluid, 99%.

These figures are approximate and average. The water content of the tissues and organs varies from time to time according to the loss and supply of water and the degree of activity.

It must be remembered that the water content of the body is derived from two sources—

(b) As end product of metabolism.

It is better to call the former as exogenous water and the latter as endogenous water.

The body water remains in two states:

(a) in the free state, i.e., not combined with anything. Most of the body water remains in this form. Various substances can remain dissolved in this water and be removed by ultrafiltration,

(b) Bound water. This is a very small quantity. In this form water remains combined with the colloids and other substances.

Metabolic Water (Endogenous Water):

This water comes as an end product of metabolism. Almost the whole of H of solid food is converted into wa­ter, only about 5 gm of H being excreted in the form of ammonia, urea, etc. Different foodstuffs yield different quantities of water.

Approximate figures are given below:

Functions of Water:

Some of the important physiological functions of water are summarised below:

i. It is an essential constituent of living cell. No living thing can resist drying.

ii. By its Solvent Action:

By its solvent action it forms a great number of crystalloidal and colloidal solutions and thus serves as a universal medium in which the intracellular and extracellular chemical reactions take place. Probably no chemical reaction inside the body can take place without water.

iii. It Acts as a Medium for Various Physical Processes:

It acts as a medium for various physical processes, such as osmosis, diffusion, filtration, etc.

It is an important chemical process involved in digestion and metabolism. In this process the H and OH ions of water are introduced into bigger molecules and the latter are broken down into smaller units.

v. Dehydration and Condensation:

In these processes water molecule is removed. This takes place in certain synthetic processes in which bigger particles are formed by the union of smaller ones. For instance, glyco­gen from glucose. This action is the reverse of hydrolysis.

Water is a very good ionising medium. The dielectric constant of water being very high, oppositely charged ions can coexist in water without much interference.

vii. It Acts as a Vehicle for Various Physiological Processes:

(a) For absorption of food material from the intestine

(b) For reabsorption from kidney tubules

(c) For the transport of the various food stuffs from place to place

(d) For the drainage and excretion of the end products of metabolism

(e) For the manufac­ture of various secretions, such as, digestive juices, etc.,

(f) For carrying the hormones to their places of activity, etc.

The physical and chemical properties of water permit chemical reactions requiring large amounts of heat to take place at a low body temperature.

Body temperature is regulated by water in the following ways:

(a) Heat absorption — Due to high specific heat of water more heat is required to raise the temperature of 1 gm of water through 1°C, than most of known solids and liquids. By virtue of this property water can mop up large quantity of heat,

(b) Heat conduction and distribution—Heat-conducting power of water being very high it acts as a very good agent in carrying away heat from the site of production and distributing it throughout the body. By the two above properties, water acts as an important part in regulating body heat.

Water acts as a lubricant to prevent friction and drying. In joints, pleura, peritoneum, conjunctiva, etc., the aqueous solution is practically free from fats and acts as a lubricant against rubbing and drying.

The aqueous humour helps to keep up the shape and tension of the eye-ball and acts as a refractive medium for light.

The cerebrospinal fluid which contains nearly 99% water acts as a great mechanical buffer preventing injury to the nervous system.

xii. Respiratory Function:

Although CO2 and O2 are only slightly soluble in water, yet this little solubility is of immense importance for the gaseous exchange in the tissues and lungs. The fish derive oxygen almost exclusively from dissolved O2 in water.

Water Balance:

Water is continuously being supplied and lost from the body. But still the total water content of the body is kept more or less constant, by maintaining a balance between supply and loss. This indicates that there must be efficient machinery for maintaining water balance.

Water Requirement:

The total water requirement of an adult, under ordinary conditions, is about 2,500-3,000 ml, i.e., about 1 ml per calorie of food intake. Half of this quantity (i.e., about 1,500 ml or half ml per calorie) should be taken as free drinks.

The above figures are average and approximate. Water loss by any one of the channels may rise or fall under various conditions. Loss through skin varies according to the temperature and humidity of the atmo­sphere and also upon the amount of muscular exercise done. In hot climates and with exercise, excretion through skin may vary from 3—10 litres per day. Higher atmospheric humidity reduces water loss through the skin.

Water excretion, by lungs also increases in hot dry weather. In diarrhoea, dysentery, cholera, etc., more water is lost in the faeces, while in conditions of diuresis more is passed out by the kidneys. The water secreted in the digestive juices is not lost water. Because it is almost completely reabsorbed and about 5—7 litres of water circulate in this way per day. The loss in saliva and lachrymal secretion is negligible under nor­mal conditions.

Positive and Negative Water Balance:

Water balance is said to be positive (intake exceeds loss) in growing infants and children, in convalescents, athletes and pregnant women who are storing water and building their body tissues. Each gram of protein is laid down with about 3 gm of water. Fat and glycogen are deposited with less amount of water. When diet is changed from high fat to high carbohydrate, water retention takes place and the balance becomes positive.

Water balance is negative (loss exceeds intake) under the following conditions:

(a) When the subject is thirsty,

(b) When a pre-existing oedema is clearing up due to diuresis, and

(c) When diet is changed from high carbohy­drate to high fat.

In any condition of increased water loss, the relative proportion of Na and K content of the fluid excretion will indicate whether the water is coming chiefly from the extracellular or intracellular sources. High Na content will indicate extracellular source, whereas high K content will indicate intracellular source, provided intake remains constant.

Regulation of Water Balance:

In spite of large amount of water is constantly appearing in and disappearing from the body, a fairly accurate balance is maintained between its gain and loss, which indicates that there must be a strong regulating machinery. The mechanism which regulates water balance is very intricate and is not yet fully known.

The following factors are closely involved in it:

(ii) Autonomic nervous system—hypothalamus and the vasomotor system,

The roles of these factors are discussed below:

A number of endocrines take part in water regulation.

a. Posterior Pituitary:

It manufactures two hormones, e.g., antidiuretic hormones or vasopressin and oxytocin, of which antidiuretic hormone has got influence upon water balance (Fig. 10.118). The antidiuretic hormone—This increases the reabsorption of water from the distal renal tubules and thus reduces urine volume. It is very interesting to note that the secretion of this hormone is controlled by the water content of the body. Excess of water depresses, while dehydration stimulates the secretion of this hormone. In the thirsting animals the presence of an antidiuretic substance has been demonstrated in the urine.

Adrenal cortex secretes aldosterone which plays an important part in maintenance of water balance. The secretion of aldosterone is controlled by the angiotensin II and also by high serum K + and low serum Na + . The aldosterones regulate the water balance through ADH release from posterior pituitary, causing retention of water and thus increase of blood volume (Fig. 10.118).

In adrenal cortical insufficiency there is decreased reabsorption of Na + and as a result more Na + is lost in the urine. There is increased reabsorption of K + . The reabsorbtion of CI is also depressed. There is a consequential change in the body fluids. The intracellular crystalloid osmotic pressure exceeds that of the extracellular crys­talloid osmotic pressure, and water flows from the extracellular fluid to the intracellular fluid. Plasma volume decreases, and there is anhydraemia and haemoconcentration.

Injection of adrenaline reduces renal circulation by causing constriction of renal vessels and thus decreases the volume of urine.

Thyroxine increases urine volume along with increased elimination of salt, probably not by a direct effect on the kidney but by raising the general metabolism and thus increasing nitrogenous end products which acted as diuretics. In myxoedema there is increased fluid retention in the extracellular tissue.

ii. The Autonomic Nervous System:

The hypothalamus controls the secretion of antidiuretic hormone of the posterior pituitary through the supra-opticohypophyseal tract. Lesion of this tract or the corresponding region of hypothalamus or disease of the posterior pituitary causes intense polyuria known as diabetes insipidus.

The function of hypothalamus may be controlled in the following way: the water content of the body- excess water dilutes blood and reduces osmotic pressure as a result of which the hypothalamus is depressed leading to less secretion of anti-diuretic hormone and consequently diuresis is produced. When body water is reduced, the osmotic pressure of blood increases, hypothalamus is stimulated— more antidiuretic hormone is secreted and consequently urine volume is reduced.

The vasoconstrictor and vasodilator nerves also play an important role in the regulation of renal circulation and general blood pressure.

When water content of the body rises, such as by excess water intake, or saline injections, etc. kidneys excrete more water.

This effect may be ascribed to:

(a) Increased blood volume and consequent rise of blood pressure and thereby increased filtration pressure,

(b) Dilution of plasma proteins, reducing colloidal osmotic pressure and consequently increasing the available filtration pressure,

(c) Increasing the number of active glomeruli, and

(d) Depressing the degree of water reabsorption by the renal tubules. It has been shown that the first two effects are negligible. In man no increase of glomerular filtration takes place until the urine volume exceeds 900 ml per hour.

Regarding the third factor it has been proved that in certain species of animals, there is some increase in the number of active glomeruli under such conditions. It is doubtful whether in man this change at all takes place. But even if it is assumed that it do take place, yet this cannot explain the huge increase of urine volume which may be as much as twenty times its normal value,

(e) It has been observed that the increase of central blood volume enhances the urine output through the inhibition of secretion of ADH. It is suggested that the inhibition of ADH secretion takes place reflexly through the stimulation of stretch receptors present in the left atrial wall, and

(f) Besides these, angiotensin II which is formed by the kidney-reinn, takes an important part in regulation of water balance through the secretion of aldosterone (Fig. 10.118).

The fourth factor is, therefore, the chief agent in regulating water excretion by the kidneys under phys­iological conditions. It has been already explained how the water content controls the secretion of antidi­uretic hormone from the posterior pituitary upon which the degree of renal reabsorption depends.

iv. Respiration Lungs and Skin:

These channels also take considerable part in regulation of water balance by excreting variable amounts of water.

v. Phenomena of Thirst:

When more fluid is lost, such as, in diarrhoea, vomiting, diuresis, sweating, haemor­rhage, etc. the subject feels thirsty, and takes water. Thirst may be defined as the specific ‘hunger for water’. In this way the amount of lost water is replenished. In hibernating animals metabolism is so low that the water produced by the oxidation of foodstuffs is enough to equalise the water loss. Hence, under such condition no thirst is felt.

Drinking is stimulated by three types of stimuli:

a. A rise in vascular tonicity even without any change in blood volume.

b. A fall in blood volume even when unacompained by a rise in osmolarity.

c. A third factor which operates in some animals is a rise in temperature which can stimulate drinking even before there is any obvious change in body water content.

Little is known about the receptors which mediate the sensation of thirst. Presumably the initial sensation of thirst depends on blood volume and osmolarity changes—when appropriate amount of water has been drunk, the sensation vanishes because of the activity of oral and gastric receptors. The thirst centre is situated in the midhypothalamic region near the paraventricular nucleus (caudal to the osmoreceptors).

Thus when the water content of the body increases, the water balance is maintained in two ways:

(i) By Reducing Water Intake:

The subject does not feel thirsty and takes no water.

(ii) By Increasing Water Loss:

This is done by reducing secretion of antidiuretic hormone through hypothalamus and thus causing diuresis.

When the water content of the body is reduced (by loss, etc.)—exactly opposite processes take place and the balance is thus maintained.


4: Introduction to the Human Body - Biology

Figure 1. Flourescence-stained Cell Undergoing Mitosis. A lung cell from a newt, commonly studied for its similarity to human lung cells, is stained with fluorescent dyes. The green stain reveals mitotic spindles, red is the cell membrane and part of the cytoplasm, and the structures that appear light blue are chromosomes. This cell is in anaphase of mitosis. (credit: “Mortadelo2005”/Wikimedia Commons)

You developed from a single fertilized egg cell into the complex organism containing trillions of cells that you see when you look in a mirror. During this developmental process, early, undifferentiated cells differentiate and become specialized in their structure and function. These different cell types form specialized tissues that work in concert to perform all of the functions necessary for the living organism. Cellular and developmental biologists study how the continued division of a single cell leads to such complexity and differentiation.

Consider the difference between a structural cell in the skin and a nerve cell. A structural skin cell may be shaped like a flat plate (squamous) and live only for a short time before it is shed and replaced. Packed tightly into rows and sheets, the squamous skin cells provide a protective barrier for the cells and tissues that lie beneath. A nerve cell, on the other hand, may be shaped something like a star, sending out long processes up to a meter in length and may live for the entire lifetime of the organism. With their long winding appendages, nerve cells can communicate with one another and with other types of body cells and send rapid signals that inform the organism about its environment and allow it to interact with that environment.

These differences illustrate one very important theme that is consistent at all organizational levels of biology: the form of a structure is optimally suited to perform particular functions assigned to that structure. Keep this theme in mind as you tour the inside of a cell and are introduced to the various types of cells in the body. A primary responsibility of each cell is to contribute to homeostasis.

Homeostasis is a term used in biology that refers to a dynamic state of balance within parameters that are compatible with life. For example, living cells require a water-based environment to survive in, and there are various physical (anatomical) and physiological mechanisms that keep all of the trillions of living cells in the human body moist. This is one aspect of homeostasis. When a particular parameter, such as blood pressure or blood oxygen content, moves far enough out of homeostasis (generally becoming too high or too low), illness or disease—and sometimes death—inevitably results.

The concept of a cell started with microscopic observations of dead cork tissue by scientist Robert Hooke in 1665. Without realizing their function or importance, Hook coined the term “cell” based on the resemblance of the small subdivisions in the cork to the rooms that monks inhabited, called cells. About ten years later, Antonie van Leeuwenhoek became the first person to observe living and moving cells under a microscope. In the century that followed, the theory that cells represented the basic unit of life would develop. These tiny fluid-filled sacs house components responsible for the thousands of biochemical reactions necessary for an organism to grow and survive. In this chapter, you will learn about the major components and functions of a prototypical, generalized cell and discover some of the different types of cells in the human body.


Lecture 4: Biochemistry 3

Download the video from iTunes U or the Internet Archive.

Topics covered: Biochemistry 3

Instructors: Prof. Robert A. Weinberg

Lecture 10: Molecular Biolo.

Lecture 11: Molecular Biolo.

Lecture 12: Molecular Biolo.

Lecture 13: Gene Regulation

Lecture 14: Protein Localiz.

Lecture 15: Recombinant DNA 1

Lecture 16: Recombinant DNA 2

Lecture 17: Recombinant DNA 3

Lecture 18: Recombinant DNA 4

Lecture 19: Cell Cycle/Sign.

Lecture 26: Nervous System 1

Lecture 27: Nervous System 2

Lecture 28: Nervous System 3

Lecture 29: Stem Cells/Clon.

Lecture 30: Stem Cells/Clon.

Lecture 31: Molecular Medic.

Lecture 32: Molecular Evolu.

Lecture 33: Molecular Medic.

Lecture 34: Human Polymorph.

Lecture 35: Human Polymorph.

Among the issues that some people asked that should be discussed in greater detail should be the structure of proteins.

I'll touch on it very briefly this morning, different kinds of bonding, tertiary and quaternary structure, condensation or dehydration reactions. And, in fact, many of those issues should be addressed in the recitation sections.

That's the ideal place to begin to clarify things which although they were mentioned here may not have been mentioned in the degree of detail that you really need to assimilate them properly.

And I urge you to raise these issues with the recitation section instructors. That's exactly what they're there for.

Having said that I just want to dip back briefly into protein structure, even though we turned our back on it at the end of last time, just to reinforce some things that I realized I should have mentioned perhaps in greater detail. Here for the example are different ways of depicting the three-dimensional structure of the protein. And, by the way, we see that these are beta pleated sheets in the light brown and these are alpha helices.

There are two of them here in green, one going this way, the other going this way, a third one going this way.

And the other blue areas are not structured, i.

., they're not structured in the sense that they are in any way obviously alpha helices or beta pleated sheets.

Here's a space-filling model, a space-filling depiction of a protein. We talked about that last time. Here is a trace of the backbone, of the peptide backbone of the same protein where the side chains are left out, and obviously where one is only plotting the three-dimensional coordinates of each of the backbone atoms, CCN, CCN, CCN. Here is yet another way of plotting exactly the same protein in terms of indicating, as we just said, the structure of these alpha helices in the other regions. That is the secondary structure of this protein. And here's yet a fourth way of plotting, of depicting the same structure of the protein where roughly one is depicting the configuration of the amino acids in terms of a large sausage. Excuse me. If one were to use a space-filling model we'd go up to here. So these are just four ways of looking at the same protein with different degrees of simplification.

Another point that I thought I would like to reinforce and make was the following. We've talked about transmembrane proteins in the past.

That is, proteins which protrude through a membrane from one side to the other. And a point that I realized I'd like to make is that if we look at a transmembrane protein here's one that is starting out in the cytoplasm of a cell. And, by the way, the soluble part of the cytoplasm is sometimes called the cytosol.

Here is the lipid bilayer that we talked about at length and here is the extracellular domain of this same protein. Now, how is all this organized? Well, the fact of the matter is we discussed the fact that this hydrophobic space in the lipid bilayer is so hydrophobic that it really doesn't like to be in the presence of hydrophilic molecules, including in this case amino acids.

And what we see here is the fact that almost all of the amino acids in this region of the protein, which is called the transmembrane region of the protein because it reaches from one side to the other, are all hydrophobic or neutral amino acids which are reasonably comfortable in the hydrophobic space of the lipid bilayer.

There happens to be two apparent violators of this, glutamine and histidine. You see these two here? I mean glutamic acid and histidine. Glutamic acid and histidine.

One is negatively charged and therefore is highly hydrophilic.

The other is positively charged and is therefore highly hydrophilic.

And on the surface that would seem to violate the rule I just articulated. But the fact is that as it turns out in the particular protein these two charges, these two amino acids are so closely juxtaposed with one another that their positive and negative charges are used to neutralize one another. And as a consequence in effect there is no strong charging or polarity in this area or in this area. The take-home lesson is that somehow proteins manage to insert themselves and to remain stable in the lipid bilayer by virtue of either using only stretches of hydrophobic or nonpolar amino acids or they use tricks like this of neutralizing any charges that happen to be there. Note, by the way, that because there are hydrophilic amino acids down here and there turn out to be hydrophilic amino acid around here, arginine, and here there's a whole bunch of basic amino acids. Note that this keeps the transmembrane protein from getting pulled in one direction or the other because this arginine likes to associate with the negative phosphates on the outside of the phospholipids.

And the same thing is here. And all that means is that this transmembrane protein is firmly anchored in the lipid bilayer, a point we'll talk about later in greater detail when we talk about membrane structure. One other little point I'll mention here in passing, which we'll also get into in greater detail, is that once a protein has been polymerized that polymerization is not the last thing that happens to it once it's polymerized and folded into place because we know that proteins undergo what is called post-translational modifications. And, as we'll talk about in the coming weeks, the process of synthesizing a protein is called translation. And when we talk about post-translational modification what we're talking about is opening our eyes to the possibility that even after the primary amino acid sequence has been polymerized there are chemical alterations that can subsequently be imposed on the amino acid side chains to further modify the protein. One such modification, by example, is a proteolytic degradation. And when I talk about proteolytic degradation, I'm talking about the fact that one can break down a protein.

Proteolysis is the breaking down of a protein. And when we talk about degradation we're talking about destroying what has been synthesized.

In the case of many proteins, once they're synthesized there may be a stretch of amino acids at one end or the other that simply clipped off therefore creating a protein which is smaller than the initially synthesized product of protein synthesis, i.e.

the initially synthesized product of translation.

Here we see yet another kind of post-translational modification, because it turns out that in many proteins which protrude into the extracellular space there is yet another kind of covalent modification which is the process of glycosylation in which a series of sugar side chains, carbohydrate side chains is covalently attached to the polypeptide chain usually on serines or threonines using the hydroxyl of the side chain of serines or threonines to attach these oligosaccharide side chains.

We know from our discussion the last time oligosaccharide means an assembly of a small number of monosaccharides.

And each of these blue hexagons represents a monosaccharide which are covalently linked and also modify the extracellular domain of this protein as it protrudes into the extracellular space.

So I'm just opening our eyes to the possibility that in the future we're going to talk about yet other ways in which proteins are modified to further tune-up their structure to make them more suitable, more competent to do the various jobs to which they've been assigned.

Let's therefore return to what we talked about the last time, the fact that the structure of nucleic acids is based on this simple principle. Here, by the way, I'm returning to the notion of this numbering system.

We're talking about a pentose nucleic acid. The fact that there are two hydroxyls here right away tells us that we're looking at a ribose rather than a deoxyribose which, as I said last time, lacks this sugar right there. Note, as we've said repeatedly, that the hydroxyl side chains of carbohydrates offer numerous opportunities for using dehydration reactions, or as they're sometimes called condensation reactions where you remove a water, where you take out a water, dehydration, or we can call them condensation reactions to attach yet other things. And, in fact, in principle there are actually four different hydroxyls that could be used here to do that. There's one here, there's one here, one here and one here. There are four different hydroxyls. The 1, the 2, the 3 and the 5 hydroxyl are, in principle, opportunities for further modification.

In truth the 2-prime hydroxyl is rarely used, as we'll discuss shortly, but the main actors are therefore this hydroxyl here in which a condensation reaction has created a glycosidic bond.

That is a bond between a sugar and a non-sugar entity.

Glyco refers obviously to sugars like glycogen or glycosylation we've talked about before. Here a bond has been made between a base, and we'll talk about the different bases shortly, and the 1-prime hydroxyl of the ribose. Over here at the 5-prime hydroxyl yet another condensation reaction.

Sometimes this is called an esterification reaction.

And again esterification refers to these kinds of condensation reactions where an acid and a base react with one another, and once again through a condensation reaction, yield the removal of a water. And let's look at what's happening here, because not only is one phosphate group attached to the 5-prime carbon, to the 5-prime hydroxyl.

In fact, there are three. And they are located, and each of them has a name. The inboard one is called alpha, moving further out is beta, and furthest out is gamma.

And it turns out that this chain of phosphates have very important implications for energy metabolism and for biosynthesis.

Why? I'm glad I asked that question. Because these are all three highly negatively charged. This is negatively charged, this is and this is. And, as you know, negative charges repel one another. And as a consequence, to create a triphosphate linkage like this represents pushing together negative charged moieties, these three phosphates, even though they don't like to be next to one another. And that pushing together, that creation of the triphosphate chain represents an investment of energy. And once the three are pushed together that represents great potential energy much like a spring that has been compressed together and would just love to pop apart. These three phosphates would love to pop apart from one another by virtue of the fact that these negative charges are mutually repelling. But they cannot as long as they're in this triphosphate configuration. But once the triphosphate configuration is broken then the energy released by their leaving one another can then be exploited for yet other purposes.

Keep in mind, just to reinforce what I said a second ago, the difference between a ribose and a deoxyribose is the presence or the absence of this oxygen. And now let's focus in a little more detail on the bases because the bases are indeed the subject of much of our discussion today. And we have two basic kinds of bases. They're called nitrogenous bases, these bases, because they have nitrogen in them. And if you look at the five bases that are depicted here you'll see that they are not aromatic rings with just carbons in them like a six carbon benzene.

Rather all of them have a substantial fraction of nitrogens actually in the ring, two in the case of these pyrimidines.

And here you see the number actually is four.

In fact, one of these nitrogenous bases indicated here, guanine has actually a fifth one up here as a side chain.

This is outside of the chain, it represents a side group. And if we begin now to make distinctions between the ring itself and the entities that protrude out of the ring, they really represent some of the important distinguishing characteristics.

It's important that we understand that pyrimidines have one ring and these have two rings in them. The purines have a five and a six membered ring fused together, as you can see. The pyrimidines have only a six membered ring. And what's really important in determining their identity is not the basic pyrimidine or purine structure. It's once again the side chains that distinguish these one from the other. Here in the case of cytosine we see that there's a carbonyl here, an oxygen sticking out, and there's an amine over here. We see uracil which happens to be present in RNA but not DNA which has two carbonyls here and here.

Obviously, therefore what distinguishes these two from one another is this oxygen versus this amine.

And here we see the thymine which is present in DNA but not RNA.

And this will become very familiar to you shortly.

This looks just like uracil except for the fact that there's a methyl group sticking out here. Now, very important for our understanding of what's happening here is the fact that this methyl group, although it distinguishes thymine from uracil is itself biologically actually very important.

It's there to be sure and it's a distinguishing mark of T versus U, but the business end of T versus U in terms of encoding information happens here with these two oxygens sticking out. They're the important oxygens, here and here. And therefore from the point of view of information content, as we'll soon see, T and U are essentially equivalent. It may be that one of them happens to be in RNA and the other in DNA, but from the point of view of understanding the coding information they carry it's these two carbonyls here and here which dictate essentially their identity.

We have the same kind of dynamics that operate here in the case of A and G where once again this one has only an amine side chain and this one has a carbonyl and an amine side chain right here.

Now, very important there is a confusing array of names that are associated with all this. I don't know if it you can, well, it reads reasonably well. Because once a base, and I just showed you bases which are unattached to the sugars, once bases are attached to the sugars they change their name slightly. So keep in mind that here, when we talk about these nitrogenous bases, the bases are just free molecules where in each case this lowest nitrogen is the one that participates in the formation of a covalent glycosidic bond with the ribose or the deoxyribose underneath it. And here we can see one indication of how that, you see this N, in all cases via a condensation reaction, forms a covalent bond with a five carbon sugar, once again deoxyribose or ribose. Once the base associates with the sugar, that is the base plus the sugar is called a nucleoside.

So when we talk in polite company about a nucleoside we're not talking about free bases. We're talking about the covalent interaction of a pentose binding to a base. The pentose could be one or the other of these two. And that's what a nucleoside is.

If on top of that we add additionally one or more phosphates then we even modify our language even further because a base attached to a sugar which in turn is attached to a phosphate is called a nucleotide. The nucleotide, the T is there to designate the fact that there's actually, in addition to the base and the sugar there's a phosphate which is attached and extends off the end. And there are slightly different names. For the purposes of this course we won't get into this very arcane nomenclature because it is, to be frank, and you know I always am frank with you, confusing. Here is U.

And when uracil, the base becomes linked to a ribose it changes its name from uracil to uridine. Cytosine changes its name to cytidine when it becomes a nucleoside by a covalent linkage to either ribose or deoxyribose. Thymine becomes thymidine. And the same nomenclature exists, the shift in their names exists in the case of the purines as well, adenine becomes adenosine and so forth. We need to focus mostly on the notion of A, C, T, G and U. Those are the things we need to think about. And why is this nomenclature confusing? Well, here the nucleoside ends with osine, O-S-I-N-E. You see that here? You say that's easy to remember, but look up here. Here the base ends with O-S-I-N-E.

And so this nomenclature which was cobbled together in the early 20th century will bedevil us and generations of biology students to come. Oh well, that's life. Now, one of the things we're interested in and which I talked about briefly last time was the whole notion of polymerization, i.e., how we actually polymerize a chain. Let's look at this illustration which I think is more useful. Recall the fact that I emphasized with great seriousness the fact that nucleic acid synthesis always occurs in a certain polarity.

It goes in a certain direction. You cannot add nucleotides on one end or the other end willy-nilly. You can only add them onto the 3-prime end. And keep in mind that the reason why this is defined as the 5-prime end is that this is, the last hydroxyl sticking out at this end comes out of the 5-prime carbon right here, the 5-prime hydroxyl. And conversely at this end we're adding another base at the 3-prime hydroxyl, at this end, which creates the 3-prime end of the DNA or the RNA.

In fact, the polymerization always occurs between the 5-prime end of a deoxyribonucleotide indicated here where the bases remain anonymous and the 3-prime hydroxyl. That's the way it always happens.

And here we begin to appreciate the role of the high energy phosphate linkage. Because this high energy triphosphate linkage, which is synthesized elsewhere in the cell like a coiled spring and which contains a lot of potential energy by virtue of this mutual negative repulsion of the phosphate groups, this energy is used to form the bond here between the phosphate in this condensation reaction and the 3-prime hydroxyl.

So that requires an investment of energy. And the resulting linkage which is formed is sometimes called a phosphodiester linkage.

Why phosphodiester? Well, obviously it's phospho.

And there actually are two esterifications that are occurring here. If we look at one of these phosphodiester bonds we see that an ester linkage has been made with this hydroxyl and an ester linkage has been made with this hydroxyl. And for that reason it's called a phosphodiester linkage. Therefore we come to realize that polymerization of nucleic acids doesn't take place spontaneously.

It requires the investment of a high-energy molecule, the investment of the energy that it carries. And when this linkage is formed the diphosphate here, the beta and the gamma phosphates float off into interstellar space. It's only the alpha phosphate that is retained to form the resulting diphosphate, a phosphodiester linkage. And this process can be repeated literally thousands and millions of times. An average human's chromosomes contains on the order of tens, fifty, a hundred mega-bases of DNA.

A mega-base is a million bases or a million nucleotides.

So there you can understand that there's no limit to the extent of elongation of these various kinds of molecules. Now, note by the way yet another feature of this which is that the distinguishing feature between DNA and RNA, the most important distinguishing feature is this 2-prime hydroxyl.

And here we're talking about DNA, but we could almost in the same breath be talking about the way that RNA gets polymerized.

Why? Because this 2-prime hydroxyl or this 2-prime hydrogen in this case is out of the line of fire. The business action is happening right along here. Look where the business action is in terms of the backbone. The 2-prime hydroxyl is off to the side. And whether it's oxygen or just whether it's OH, that is in ribose, a hydroxyl group or just a hydrogen, as is indicated here in the case of deoxyribose, is irrelevant to the polymerization. And therefore we can guess or intuit, and just because we guessed doesn't mean it's wrong, often it's right, it doesn't really make much difference whether we look at DNA or RNA. Here's a polymerization scheme of RNA and it's absolutely identical to that of DNA.

In this case it's ribonucleotide triphosphates that are used for the polymerization reaction. Now here I just uttered the phrase ribonucleoside triphosphates. Why did I say that? Well, ultimately only the good Lord knows why I said that.

But let's look at this phrase. I said ribonucleoside triphosphate rather than ribonucleotide triphosphate because the fact that I added this on the end makes the T there unnecessary.

The T is there to indicate the phosphate being attached to the ribose or the deoxyribose. But if I'm adding this phrase over here, triphosphate, that obviates, that makes unnecessary my saying ribonucleotide triphosphate. If I'm looking at UTP or ATP, I would say I'm a ribonucleotide if I don't mention the triphosphate. But the moment this comes from my lips then we'll say ribonucleoside indicating that a ribonucleoside, that is a base and a sugar are then attached to one or more phosphate linkages. Now, the ultimate basis of the biological revolution comes from the realization that these different bases have complementarity to one another. That is they like to be together with one another. And if we look at this and we think about the DNA double helix we come to realize that these bases have affinities for one another. And the general affinity is one purine likes to be facing opposite one pyrimidine.

One pyrimidine opposite one purine. And if we have two pyrimidines facing one another they're not close enough to one another to kiss.

And if we have two purines they're too close to one another, they're bumping into one another, they take up too much space. And therefore the optimal configuration is one purine and one pyrimidine.

And you can see these two pairings here in the case of what happens with DNA. In fact, the realization of this diagram right here is what triggered the discovery of DNA in 1953.

This diagram right here is what triggered the biological revolution.

And though it's been depicted in many, many ways it's worthwhile dwelling on it because this is perhaps the most important diagram that we'll address all semester. Although this doesn't mean we have to spend all semester assimilating it. It's not so complicated.

It's relatively straightforward. And let's look at its features.

Let's dwell on them momentarily because this is a microscopic snapshot of what DNA is composed of. You all know it's a double helix and therefore there are two strands of DNA in a double helix.

And one of the interesting things about the double helix, although we're not showing it yet, we're just showing a little section of a double helix, is the polarity of the two chains that constitute the double helix. Let's look at that polarity.

This one is running in one direction and this one, the opposite one, the complementary one is running in the other direction. And therefore we talk about the double helix as being anti-parallel. Well, I guess I should have a bandage on the other finger to convince you but you get the idea.

They're running in opposite directions.

They're not both pointed the same. And the other thing to indicate is, to repeat what I said just seconds ago, that there's a complementarity between the purines and the pyrimidines. So we use the word complementary with great frequency, with great promiscuity in biology.

Complementarity refers to the fact that A and T here or A and U because I said U and T are functionally equivalent, they like to be opposite one another. There's a purine and a pyrimidine.

And the converse is the case with C and G, they like to be opposite one another. Now, there is specificity here.

You might say any purine can pair up with any pyrimidine, but it's not the case. For instance, A doesn't like to be opposite C and T doesn't like to be opposite G. So one of the things we have to memorize this semester, and it's not many and it's not hard, is that A and T are opposite one another, or A and U, and G and C are opposite one another. That's one of the essential concepts in molecular biology. There are now a thousand things you need to learn, but if you don't understand that then ultimately sooner or later you'll find yourself in a swamp, literally or figuratively. Now, let's look at the different between these two. One of the interesting things is, to state the obvious, the way they're associating with one another, hand in glove, is via hydrogen bonds. That's not any covalent interaction, which means they're reversible. We talked about that.

Which means that if we were to take a solution of double stranded DNA and boil it we would break those hydrogen bonds.

Remember they only have 8 kilocalories per mole and boiling water has far higher energetic content. And consequently if we heat up a DNA double helix and we break those double bonds of DNA that hold the two strands together, the two strands come apart, the DNA ends up being denatured, that is the two strands are separated one from the other. In fact, if there ever were a covalent cross-link between the two strands that's really bad news for a cell carrying such a DNA double helix. A covalently cross-link from one strand to the other DNA double helix represents often a sign that a cell should go off and die because it has a very hard time dealing with that by virtue of the fact, as we will soon learn or as you already know, the cell has, with some frequency, to pull apart these two strands. And therefore this association must be tight enough so that it's stable at body temperature but not so tight that it cannot be pulled apart when certain biological conditions call for it. You see that in fact here there are three hydrogen bonds and here there are only two hydrogen bonds. That also has its implications. It turns out to be the case that the disposition of this hydrogen and this oxygen here, they're far enough apart that for all practical purposes they don't really make very good hydrogen bonds. And therefore we think of this as having two and this having three. And if you were to try to put C opposite A or G opposite T you'd see that they cannot form hydrogen bonds well with one another. Instead they kind of bump into one another, and therefore are not complementary to one another at all.

There's another corollary that we can deduce from this diagram, and that is the following. If it's always true that A equal C and G equal T -- A equals T and G equals C. By the way, this is an interesting story. This is the Chargaff Rule. Because about a year or so before Watson and Crick figured out the structure of the double helix there was a guy named Erwin Chargaff in New York at Columbia University who one day figured out that if you looked at a whole bunch of nucleic acids, different DNAs from different cell types -- And in certain cell types what he found was that G was equal to, for example G equals 20% of the bases. Therefore, obviously we know C must equal also 20% because there always has to be a C opposite a G in the double helix, right? G and C always have to be equal. And Chargaff discovered that, in fact, A in such DNA always was 30% and T was also 30%. Well, these together make up 100% which is, we're not in higher math yet, but A and T were always the same. If you looked at another type of DNA he might find that G equals 23% and C also equals 23%. And in this same DNA then A would equal 27%, I guess, and T also equals 27%.

And I hope that adds up to 100%. So he looked at a whole bunch of DNAs and they always tracked one another, A always tracked T, G always tracked C. And then in 1953 up comes these two guys from Cambridge, England, Watson and Crick whom Chargaff regarded as upstarts, as smart-asses who thought they knew all the answers. And Watson and Crick said, gee, this Chargaff rule really is very interesting because it suggests something about the structure of DNA. These cannot just be coincidences.

There's something profoundly important they said, correctly, in the fact that there was always an equivalence between A and T and between G and C. And that represented one of the conceptual cornerstones of their elucidating the structure of the double helix. And so Chargaff who died last year or the year before last, at an advanced age, was for the next fifty years a very bitter man, because he was this far away from figuring out this far. Not this far, but this far away from figuring out, making the most important discovery in biology in the 20th century. He had the information right there.

And if he thought a little bit about information theory and thought a little bit about the way information content is encoded he could have already predicted, not the detailed structure of the double helix, but at least the way in which it encodes information.

Because, to state the obvious, and as many of you know already, if one looks at the structure of a double helix one can, in principle, depict it in a two or a three-dimensional cartoon.

Here's the way one can think of it. This is the way we've been talking about it over the last couple of minutes. It's a two-dimensional double helix. And from the point of view of information encoding, it doesn't really matter whether we draw it this way or that way. It happens that the double helix is turned around like that, it's twisted around. It's very difficult for biological molecules to be totally flat for an extended period. And the helix is, in fact, something that is frequently resorted to. Witness the alpha helix in the protein. So these are turned around. It turns out that each of these constitutes a base pair, and each of these base pairs is, in fact, 3.4 angstroms apart. 3.4 angstroms thick.

So you have ten of them, the DNA helix advances 3.4 angstroms every ten turns. And ten turns is roughly, oh, I'm sorry. Ten base pairs is roughly one turn of the alpha helix.

So if you go here and you count up ten, we should start again at the same orientation. Another ten is another turn.

Another ten is another turn. In fact, I'm just recalling that I was once a TA in 7. 1 in 1965. And there was a physics professor who became a biologist who always talked about these double helices. And he always talked about the measurements of different DNA molecules. Now, you may know that the term angstrom is named after a Danish person named Angstrom.

That's why it got its name. So whenever this professor, whom I never corrected, God forbid, ever talked about something that was ten angstroms long, he called these ten angstra.

Now, as you know, when you go in a Latin verb from singular to plural it's “-um” to “-a”, right? So he pretended this was a Latin word. What's a good word?

Sorry? What's a common Latin word we use? Sorry?

Millennium. Yeah, millennium, millennia.

So he went from angstrom to anstra. And it went on for a whole year. I never said anything but I knew better. OK, anyhow.

Here you see the genius of Watson and Crick. And, by the way, Angstrom was a Dane, as I said, and not a Roman soldier.

So here we see. OK. So here is the genius of their discovery. And the elegance of it is not how complicated it is.

The elegance of it is how simple it is, because information we see is encoded in two strands. The information is redundant because if we know the sequence of one strand we can obviously predict the sequence in the other strand because it's a complementary sequence. If we always realize that A is opposite T and G is opposite C we can know directly that a sequence in one strand, which may be A, C, T, G, G, C and the other strand moving in the other anti-parallel direction the sequence is like this.

I don't need to know the sequence of the other strand.

I can predict it by using these rules of complementary sequence structure. And that, in turn, obviously has important implications. If we look at the three-dimensional structure, this is more of what's called a space-filing model.

This is the way the x-ray crystallographer would actually depict it. We talked about space-filling models before.

One of the things we appreciate is the fact that the phosphates are on the outside and these bases are in the inside. And because these bases are able also to stack with one another via hydrophobic interactions importantly the bases are protected. The face where they interact is protected from the outside world. What do I mean by that? Well, let's go back to this figure right here. You see the interaction faces between A and T or C and G they're not on the outside of the helix.

They're hidden in the middle. And that's important because it means that these interactions between A and C and G and T, you can see it up here as well, are biochemically protected from any accidents that might happen on the outside.

They're sheltered from that. And that's important because the information content in DNA must be held very stable, very constant. If it isn't then we have real trouble like cancer.

And therefore whenever a cell divides and copies its DNA, its three billion base pairs of DNA, whenever that happens the number of mistakes that are made is only three or four or five out three billion.

A stunningly low rate. And this DNA can sit around.

I told you about Neanderthal DNA that can sit around for 30, 00 years and it's chemically relatively stable.

In part, a testimonial to the fact that this base pairing, the face where the two bases interact across one another, this is shielded from the outside world because it's tucked into the middle, these interaction faces here. This is the inside of the helix.

Here the sugar phosphate groups are on the outside.

In fact, when Watson and Crick were struggling with the structure of the double helix they were in a horse race with a man named Linus Pauling who was really the inventor, the discoverer of the hydrogen bond pretty much who actually got two Nobel Prizes in his lifetime who ended his life believing that if you took enough vitamin C grams of it every day you would never get sick. I don't know what he died of, but probably like Dr. Atkins he probably died of an illness he was trying to ward off. Or he might have died of kidney failure from all the vitamin C he was putting into his body.

Who knows? Anyhow, I digress. The fact is that Pauling thought that, in fact, DNA was constituted of a triple helix, with three strands, and that the bases were facing outward. Well, of course, now we can snicker, now we can laugh, but at the time nobody had any idea.

Now we realize it's only a double helix and the bases are facing inward. And, of course, because Pauling worked with that preconception, he was never able to figure what was actually going on, even though Watson and Crick thought that he had the answer and was about to scoop them. Implicit in what I've just said is the notion that the structure of DNA, which we'll talk about later, allows it to be copied, i.e., now we're referring in passing, and we'll get into this in greater detail later, to the whole process of replication. Because if we have genetic material and we've created in a certain sequence we must be able to make more copies of it. Keep in mind that each one of us, as I mentioned to you some lectures ago, we start out with a fertilized egg with one human genome, and through our lifetimes we produce how many cells? Anybody remember?

I did mention it, right? Is there one soul who remembers it?

Remember the whole story of Sodom and Gomorrah where the Lord says if there's one soul, one righteous soul in the city I will spare the city. And of course there wasn't so he wiped them all out. 30 trillion? Well, sorry. What do we do for him? Something nice. [APPLAUSE] Excellent. OK. You'll remain anonymous, though. You won't be on that video. OK. Ten to the sixteenth cell divisions in a human lifetime. And on every one of those occasions the double helix is copied. I'm telling you that only to give you the most dramatic demonstration of the fact that if you have one set of DNA molecules you need to be able to copy it, you need to be able to replicate it. And that replicative ability is inherent in the double helix as Watson and Crick immediately said and as they noted at the end of their paper when -- I think the last sentence says it has not escaped our attention that this structure, i.e., the structure of the double helix, allows for copying, allows for replication. Because if you pull the two strands apart, recall we said earlier that in certain biological situations you need to do that, if the two strands are pulled apart not by putting them in boiling water but by enzymes whose dedicated function it is to separate the two strands.

Then when that happens one can begin to create two new daughter double helices by simply adding on new bases and thereby replicating the DNA. And how that happens is, of course, as you know, IO "Intuitively Obvious". OK. Uh-oh, we're in a dyslexic moment. Now, the fact is I emphasized with great vigor and conviction -- And remember, class, when somebody is convinced of something more often than not they're just wrong in a loud voice. But I nevertheless emphasized with great conviction that T and U are, from an information standpoint, functionally equivalent. They're replaceable, interchangeable. And therefore if we want we can make an RNA copy of a DNA molecule by realizing that if this were DNA we could make an RNA that was complementary to a DNA strand realizing that when the RNA molecule was being polymerized, instead of using T one would use U. All the other three bases are functionally equivalent. And so we could, in principle, and indeed it happens transiently, we could make a DNA-RNA hybrid helix where a DNA molecule is wrapped around an RNA molecule because the two molecules are functionally equivalent. The only difference between the two strands would be, well, there are two differences.

One, in the RNA strand we'd have a U instead of a T.

And, two, in the RNA strand all the sugars would be ribose rather than deoxyribose. Right on. OK. Good. So this structure, the simplicity of the structure gives one enormous power in encoding all kinds of information and replicating it.

What it means, as we'll discuss also in great detail later, is that if we have a certain sequence of bases in the double helix of DNA an RNA molecule could be made to copy one of the two strands to make a complementary copy.

And that RNA molecule could then leave the DNA double helix having lifted one of the sequences from it and then move to another part of the cell where it might do something interesting. And therefore to extract information out of the double helix doesn't necessarily mean to destroy it. If one can copy one of the two double strands in a complementary form as an RNA molecule that may enable the information that is encoded in the DNA to be copied without destroying the double helix itself.

Again, that process, which we'll also talk about later, is called the process of transcription.

And so in the course of this morning I have uttered the three words which represent the cannon, the basic fundaments of molecular biology. What are the three words? Replication, transcription and translation. Transcription means when you make an RNA copy of a strand of the DNA double helix. Let's just add a couple more footnotes to what I've been saying just so we are on firm ground for subsequent discussions. It turns out that often in RNA molecules they can form intramolecular double helices.

There's no reason why you cannot make a double helix out of RNA as you can make out of DNA. And therefore you see often in many kinds of RNA molecules they will hydrogen bond to themselves using these complementary sequences. And this is called a hairpin, by the way for obvious reasons. And so many RNA molecules, most of them in fact have these intramolecular hydrogen bonded double helices with confers on them very specific structure.

One other aspect of the two versus three hydrogen bonds is the following. If a double helix has many Gs and Cs then it's going to have more hydrogen bonds holding it together than if it has few Gs and Cs. So let's look at the Chargaff example. Chargaff who lived for fifty years stewing in his own bile in bitterness because he couldn't figure this out, which is exactly what happened by the way.

And so here this has a higher G plus C content, the one on the right than this one. This is 23% or 46% G plus C. This is 40% G plus C.

If it's 46% G plus C that means there are more hydrogen bonds holding the two strands together. And it turns out that if you want to denature a double helix that has high G plus C content you need to put in more energy, you need to heat the double helix up to a higher temperature. It's more difficult to pull the strands apart. One other side comment on what I wanted to say is the following. The presence or the absence of this hydroxyl here in RNA has an important consequence for the stability of RNA and DNA. Let's look at what happens to an RNA chain when a hydroxyl ion, which happens to be floating around at a low concentration, happens to attack this phosphodiester bond. What happens is that this phosphodiester bond will tend to cyclize. It's forming this five membered ring. And ultimately that will resolve and break causing a cleavage of the RNA chain. This phosphodiester bond now forming a cyclic structure here as an intermediate representing the precursor to the ultimately cleaved chain. That means that if you take RNA molecules and you put them in alkali they will fall apart very quickly for this very reason. What happens to DNA molecules when you put them in alkali? Nothing. They're alkali resistant because there isn't a hydroxyl there to form this five membered ring.

And therefore alkali cannot cleave apart the DNA or the DNA phosphodiester bond. If we imagine that OH groups, that hydroxyls, are present at a certain, albeit a certain concentration, albeit a low concentration in neutral water we can see that even at neutral pH with a certain frequency RNA molecules will slowly hydrolyze.

They'll certainly be slowly broken down by the hydroxyl ions.

DNA molecules, however, will not. And that represents yet another important biochemical reason why DNA is chemically stable and why it can carry information over years, decades or tens of thousands of years, because the phosphodiester linkage in DNA rather than RNA is very stable chemically and can hold these adjacent nucleotides together, one to the other. See you on Friday morning.


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