11.5: Overview of amino acid catabolism and several examples - Biology

11.5: Overview of amino acid catabolism and several examples - Biology

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11.5: Overview of amino acid catabolism and several examples

Disorders of amino acid metabolism

Twenty amino acids, including nine that cannot be synthesized in humans and must be obtained through food, are involved in metabolism. Amino acids are the building blocks of proteins some also function as or are synthesized into important molecules in the body such as neurotransmitters, hormones, pigments, and oxygen-carrying molecules. Each amino acid is further broken down into ammonia, carbon dioxide, and water. Disorders that affect the metabolism of amino acids include phenylketonuria, tyrosinemia, homocystinuria, non-ketotic hyperglycinemia, and maple syrup urine disease. These disorders are autosomal recessive, and all may be diagnosed by analyzing amino acid concentrations in body fluids. (Maple syrup urine disease also features the production of organic acids and is discussed in the section Organic acidemias.)

Phenylketonuria (PKU) is caused by decreased activity of phenylalanine hydroxylase (PAH), an enzyme that converts the amino acid phenylalanine to tyrosine, a precursor of several important hormones and skin, hair, and eye pigments. Decreased PAH activity results in accumulation of phenylalanine and a decreased amount of tyrosine and other metabolites. Persistent high levels of phenylalanine in the blood in turn result in progressive developmental delay, a small head circumference, behaviour disturbances, and seizures. Due to a decreased amount of the pigment melanin, persons with PKU tend to have lighter features, such as blond hair and blue eyes, than other family members who do not have the disease. Treatment with special formulas and with foods low in phenylalanine and protein can reduce phenylalanine levels to normal and maintain normal intelligence. However, rare cases of PKU that result from impaired metabolism of biopterin, an essential cofactor in the phenylalanine hydroxylase reaction, may not consistently respond to therapy.

Classic (hepatorenal or type I) tyrosinemia is caused by a deficiency of fumarylacetoacetate hydrolase (FAH), the last enzyme in tyrosine catabolism. Features of classic tyrosinemia include severe liver disease, unsatisfactory weight gain, peripheral nerve disease, and kidney defects. Approximately 40 percent of persons with the disorder develop liver cancer by the age of 5 if untreated. Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of the tyrosine catabolic pathway, prevents the production of toxic metabolites. Although this leads to improvement of liver, kidney, and neurological symptoms, the occurrence of liver cancer may not be prevented. Liver transplantation may be required for severe liver disease or if cancer develops. A benign, transient neonatal form of tyrosinemia, responsive to protein restriction and vitamin C therapy, also exists.

Homocystinuria is caused by a defect in cystathionine beta-synthase (or β-synthase), an enzyme that participates in the metabolism of methionine, which leads to an accumulation of homocysteine. Symptoms include a pronounced flush of the cheeks, a tall, thin frame, lens dislocation, vascular disease, and thinning of the bones (osteoporosis). Intellectual disability and psychiatric disorders also may be present. Approximately 50 percent of persons with homocystinuria are responsive to treatment with vitamin B6 (pyridoxine), and these individuals tend to have a better intellectual prognosis. Therapy with folic acid, betaine (a medication that removes extra homocysteine from the body), aspirin, and dietary restriction of protein and methionine also may be of benefit.

Non-ketotic hyperglycinemia is characterized by seizures, low muscle tone, hiccups, breath holding, and severe developmental impairment. It is caused by elevated levels of the neurotransmitter glycine in the central nervous system, which in turn are caused by a defect in the enzyme system responsible for cleaving the amino acid glycine. Drugs that block the action of glycine (e.g., dextromethorphan), a low-protein diet, and glycine-scavenging medications (e.g., sodium benzoate) may ease symptoms, but there is no cure for this severe condition.

Recent progress in production of amino acid-derived chemicals using Corynebacterium glutamicum

Green chemical production by microbial processes is critical for the development of a sustainable society in the twenty-first century. Among the important industrial microorganisms, the gram-positive bacterium Corynebacterium glutamicum has been utilized for amino acid fermentation, which is one of the largest microbial-based industries. To date, several amino acids, including L-glutamic acid, L-lysine, and L-threonine, have been produced by C. glutamicum. The capability to produce substantial amounts of amino acids has gained immense attention because the amino acids can be used as a precursor to produce other high-value-added chemicals. Recent developments in metabolic engineering and synthetic biology technologies have enabled the extension of metabolic pathways from amino acids. The present review provides an overview of the recent progress in the microbial production of amino acid-derived bio-based monomers such as 1,4-diaminobutane, 1,5-diaminopentane, glutaric acid, 5-aminolevulinic acid, L-pipecolic acid, 4-amino-1-butanol, and 5-aminolevulinic acid, as well as building blocks for healthcare products and pharmaceuticals such as ectoine, L-theanine, and gamma-aminobutyric acid by metabolically engineered C. glutamicum.

Keywords: Amino acids Corynebacterium glutamicum Metabolic engineering Synthetic biology Value‐added chemicals.

11.5: Overview of amino acid catabolism and several examples - Biology

Arg has a role to improve intestinal health. Increased activity of several intestinal enzymes and changed composition of the intestinal microbiota

The low glucose turnover rate reported in fish as compared to other animals (mammals and birds) is in agreement with the fact that proteins play a large role in ATP production in most ectothermic fish [67,71,72]. This is supported by the lower nitrogen retention in ectothermic fish such as carp (30%) feeding diets with increased carbohydrate content, as compared with homeotherms like pigs (45%) and chickens (50%) [39]. AAs are not only oxidized for ATP production, but they are also used to synthesize macromolecules such as proteins in the gills or other organs, and for the osmoregulation during fish seawater acclimation [73]. Osmotic pressures in teleost fish are regulated at nearly constant levels. The non-essential AAs seem to be preferentially used for osmoregulatory proposes, rather than the ten AAs considered essential for the fish, namely arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine [2]. However, the role of AAs as oxidative substrates in specific tissues has been largely neglected in previous studies that examined the effects of environmental salinity on the AA composition of fish plasma and tissues [74]. Some specific aspects of AA metabolism in different fish tissues are discussed in the following sections.

Changes in the plasma levels of AAs at various time intervals after feeding have been monitored for several species, including rainbow trout [75], carp [76], tilapia [77], and channel catfish [78]. The enzyme glutamate dehydrogenase showed moderate activities in rainbow trout and carp erythrocytes, where glutamine was more important than glucose as an oxidative substrate [79]. Glutamate is used for the synthesis of glutamine and glutathione. Glutamine is essential for the synthesis of purines and pyrimidines, whereas glutathione protects cells from oxidative stress [1].

The metabolic reactions in the liver greatly affect the concentration of most AAs in blood and gut. Liver monitors the absorbed dietary AAs arriving from the portal blood and has the important role of controlling their catabolism and release into the general circulation. Much of the AAs taken up by the liver are rapidly degraded [80]. A rapid catabolism of excess dietary AAs was observed in rainbow trout by measuring a large increase in ammonia excretions within four hours of feeding a high protein meal [81]. In the case of BCAAs, skeletal muscles may be more important for initiating BCAA degradation than the liver [71,82].

During feed deprivation, fish appears to use catabolic energy conservation strategies to meet caloric needs while minimizing tissue energy loss [83]. It has been suggested that white muscle proteolysis is the source for increased plasma levels of free AAs observed during long-term feed deprivation, normally constituting the primary source of energy in carnivorous species [54]. Furthermore, AAs can supply glucose during periods of prolonged starvation via gluconeogenesis. In several fish species, long-term starvation mobilizes muscle protein by increasing the levels of free AA, usually alanine and glutamine, the most released AAs [36,53]. The increases in plasma AAs augment their metabolic utilization [54] and this is apparently the case for most non-essential glucogenic AAs in teleost fish [84].

AAs release via proteolysis of white muscle has been identified as an important fuel source for sockeye salmon (Oncorhynchus nerka) during periods of prolonged starvation [36]. However, the total plasma AAs in starved lake sturgeon (Acipenser fulvescens) was found to be unchanged during 45 days of feed deprivation [45]. Moreover, starved brown trout (Salmo trutta) showed a significant increase in total plasma AA levels after 15 days of feed deprivation [85]. These different responses in different studies may reflect species-specific metabolic adaptation strategies in response to feed deprivation and/or differences in body energy stores, such as lipids and glycogen. In this regard, Solea senegalensis is characterized by low body lipid stores, which supports the importance of proteolysis during prolonged feed deprivation in this species [55]. The increased levels of plasma glutamine, ornithine, and arginine observed in ureotelic fish that had been feed-deprived for 21 days may facilitate detoxification of ammonia production after AA catabolism. Glutamine is formed from glutamate and ammonia, and this reaction is a cellular mechanism for ammonia detoxification in fish. However, for every mole of ammonia detoxified, two equivalent moles of ATP are hydrolyzed [86]. Higher plasma levels of serine, asparagine, glutamine, arginine, and ornithine were observed in fish (S. senegalensis) that had been feed-deprived for 21 days [87]. This may suggest their role as important sources of carbons for gluconeogenesis, which is in line with the high rates of 14 C incorporation from 14 C-labeled serine and asparagine into glucose in isolated hepatocytes from feed-deprived O. mykiss. In addition, glutamine, arginine, and ornithine can be metabolized to glutamate, and deamination of glutamate is a main pathway for its oxidation to CO2 or for gluconeogenesis in the fish liver [20].

Liver plays an essential role on controlling the mobilization of energetic reserves for survival during the starvation period. In the fed state, sulfur AAs are used for the synthesis of taurine, which is required for the production of bile salts to promote lipid digestion and absorption. However, under starvation conditions, methionine is not needed to produce bile salts and, therefore, might be used as a glucogenic AA to produce glucose as a possible energy source for the central nervous system and red blood cells [45,46]. Valine and isoleucine are glucogenic, being catabolized via the TCA cycle and utilized for gluconeogenesis (Figure 1). Moreover, glutamate and glutamine are oxidized extensively in the liver of zebrafish and hybrid striped bass, with the rate of CO2 production from glutamine being greater than that from glutamate [11], while catfish hepatocytes produce five times more ammonia from glutamine than from glutamate [88]. Ketogenic AAs are converted to acetyl-CoA or ketone bodies in order to provide energy for tissues such as the brain and heart during starvation [47,89]. The analysis of stable isotopes in different tissues has been widely used in ecological studies to learn about the nutrient transfer across ecosystem boundaries and to understand trophic relationships and the migration of animals (including fish) through dietary changes that occur throughout their lives [9].

The juvenile yellowtail amberjack (Seriola lalandi) was subjected to an isotopically equilibrated diet of δ 13 C and δ 15 N AAs and proteins for 60 days and after this period, two treatments were carried out [90]. For one treatment, the fish continued to be fed and those in the other group were deprived of feed. The compound-specific isotopic analysis (CSIA) of AAs from different tissues showed significant differences between the muscle and liver samples of the control group and those fed the test diet. The CSIA for the δ 15 N values of liver AAs revealed the largest changes relative to the diet for non-essential AAs, whereas glycine and lysine remained constant. However, methionine was the most enriched AA within the control group, as compared to test diet. Valine and isoleucine, both essential AAs, were highly enriched in the liver of starved fish, a condition arising from either a high rate of utilization or an insufficient dietary supply. Enrichment patterns were observed for alanine, aspartate, and glutamate [90].

Salmonid fish encounter periods of little or no feed intake for many reasons, such as low feed availability during winter conditions. The role of carbohydrates and proteins as energy sources during periods of short-term fasting (days to weeks) or long-term starvation (months) in different fish species is less clear [50,91,92]. In coho salmon (Oncorhynchus kisutch), liver glycogen decreases one week after the initiation of fasting, but returns to a normal level after three additional weeks of feed deprivation. Net protein breakdown has been observed during prolonged periods of feed deprivation in salmonids, but not during the initial phase [50,91]. Juvenile salmonids are potentially more sensitive to fasting than adult fish, although there are still similarities between the different life stages in protein metabolism during fasting [93]. Alanine is likely used as a substrate for glycogen and/or glucose production in the liver [48,50], but may also be oxidized in the liver and used as a direct energy source [49]. In this scenario, decreased levels of alanine in the liver of fasted fish have been demonstrated [93].

Some genetic parameters have been considered in experiments involving food-deprived and well-fed amberjack fish, in particular changes in liver leptin (LepA1 and LepA2) expression [90]. An increase in liver leptin expression was previously observed during fasting/feed restriction, similar to the increase reported in Atlantic salmon [94,95]. The activity of enzymes involved in lipid metabolism (glucose 6-phosphate dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase) and glycolysis (pyruvate kinase) appeared inversely correlated to liver leptin expression in food-deprived fish. The highest activity of these enzymes was recorded concurrently with low liver leptin expression in well-fed fish. Moreover, such interrelationships were not observed for enzymes involved in AA metabolism and gluconeogenesis [69]. Liver metabolic responses to increased dietary carbohydrates in both carnivorous fish and tilapia were also investigated as an attempt to understand the reasons for the higher metabolic use of carbohydrates in omnivorous fish than in carnivorous fish [96,97]. Some studies demonstrated that the liver of omnivorous fish responds well at the metabolic level to dietary carbohydrates, similarly to previous reports on juvenile tilapia and hybrid tilapia [98,99].

Biochemical responses to dietary nutrients in tilapia liver were previously investigated [100-102]. Gene expression studies showed no regulation at mRNA levels for metabolic enzymes related to glycolysis and gluconeogenesis, whereas mRNA levels for hepatic enzymes involved in AA catabolism were clearly dependent on the amount of dietary protein intake. This was not an expected result, as increased lipogenic and decreased gluconeogenic enzyme activities were observed in tilapia feeding carbohydrate-rich diets [103]. This indicates that enzymes in tilapia liver did not respond to dietary carbohydrates at the transcriptional level. Although the first steps of glucose utilization via the hepatic glucokinase (gck gene) were clearly higher in fish fed higher carbohydrate diets, the long-term adaptation of tilapia to carbohydrates does not necessitate persistent molecular adaptation for glucose utilization within the liver of this fish. It is unknown how the liver of carnivorous fish respond to dietary carbohydrate intake.

Although the intestine uses both Glu and Gln as energy sources, the supply of each molecule is different. Both dietary and arterial Gln content are recruited into intestinal cells, while almost all Glu utilized in the gut comes from the lumen [104]. Glu is a non-essential AA that universally exists in living organisms. It plays various roles in enterocytes metabolism and physiology, either directly, as an energy source [56] or excitatory neurotransmitter in the enteric nervous system [105], or through conversion into bioactive molecules, such as glutathione [58]. Glu serving as a substrate for the synthesis of glutathione by the intestinal mucosa is derived from enteral Glu rather than arterial Glu, and 95% of dietary Glu is metabolized as a major energy source by the intestinal cells of piglets [59]. Although Glu can be synthesized in the body, this metabolic pathway is inadequate to meet the requirement of the piglet small intestine for glutamate [106]. These studies indicate that the utilization of dietary Glu has an important role in gut health and systemic metabolism. Examining this role may be helpful to better understand AA metabolism in the intestines of fish.

Moreover, after protein hydrolysis in the gut, the AAs are absorbed and pass along the portal system to the liver. During their passage across the intestinal wall, AAs can be incorporated into intestinal proteins (constitutive or secretory) or catabolized by the tissue [68]. The gut itself can metabolize extensive amounts of certain AAs, such as glutamate and aspartate. Indeed, in some animals, gut metabolism has a major influence on the whole body AA requirement [56].

Besides glucose, ketone bodies and possibly both lipids and proteins may act as energy sources in the brain of several vertebrates [107]. Astrocytes can use glutamine as an energy source and produce glutamine from glutamate (a neurotransmitter removed from the synaptic cleft), as well as from precursors, such as glucose and fatty acids [42]. The synthesis and utilization of substrates such as glutamine, ketone bodies and lactate are greatly influenced by their concentrations in the cells and the extracellular milieu [108,109]. The carbon skeletons of glutamate are mainly metabolized into CO2, lactate, or alanine, while the nitrogen of glutamate is utilized for the synthesis of other AAs such as glutamine, proline, and arginine [57,59,110]. Glutamine has various functions in cellular metabolism, such as serving as energy fuel and being a precursor for purine and pyrimidine nucleotides, NAD + , and amino sugars [57,58].

Proteins may play an important role in fueling muscle work in fish, but their exact contribution has yet to be established [111]. The design of reliable methods to measure substrate fluxes in fish muscle [112] has allowed researchers to start investigating how fish muscles respond to common environmental stresses. White muscle under stress is forced to produce lactate at higher rates than can be processed by aerobic tissues. However, lactate accumulation is minimized because disposal is also strongly stimulated. Trout have a much higher capacity to metabolize lactate under normoxic conditions than during hypoxia or intense swimming. The low density of monocarboxylate transporters and lack of up-regulation with exercise explain the phenomenon of lactate retention in white muscle. This tissue operates as an almost-closed system, where glycogen stores act as an “energy spring” that alternates between power release during swimming and slow withdrawal in situ from lactate during recovery [111].

To cope with exogenous glucose, trout can completely suppress hepatic production and boost glucose disposal. Without these responses, glycaemia would increase four times faster and reach dangerous levels. Therefore, the capacity of salmonids to regulate glucose levels is much better than presently described in the existing literature. However, knowledge about the use of proteins or AAs as fuel for muscle work in fish is still lacking. Glutamate and glutamine are major metabolic fuels for the skeletal muscles of zebrafish and hybrid striped bass [11]. This is contrast to mammalian muscles, where fatty acids and glucose are primary energy substrates [39].

Little is known about the use of proteins as fuel for muscular work in fish, although evidence from sockeye salmon (Oncorhynchus nerka) shows that proteins become the dominant source of fuels towards the end of migration when all the other substrates reach depletion [36]. At this point, researches also reported changes in AA and protein concentrations, as well as the activities of related enzymes. AA fluxes have not been measured in exercising fish and the only direct measurement of protein catabolism during swimming was the rate of nitrogen excretion in juvenile trout with a high growth rate. However, the high growth rate may be a destabilizing factor since significant changes in the protein composition of fish tissues occur during this stage of growth. A study examined the roles of glutamate, alanine, and aspartate as gluconeogenic precursors in resting kelp bass [60], and a further research measured the fluxes of all AAs in resting rainbow trout [113]. It is unclear whether the high rates of protein catabolism observed in migrating salmon and juvenile trout are typical of active muscles or whether they only occur under exceptional circumstances of extreme exercise or rapid growth [114].

The intramuscular metabolism of ectotherms has receive little attention, but the design of reliable methods to measure substrate fluxes in fish has allowed researchers to start investigating how fish muscles respond to common stresses [112]. For example, the mudskipper (Periophthalmodon schlosseri) is quite active and levels of total free AAs increased significantly in skeletal muscle and plasma, while alanine levels increased three-fold in the muscle, four-fold in the liver, and two-fold in plasma [61]. From these results, the authors concluded that P. schlosseri was capable of partially catabolizing certain AAs to support activity on land because of its capacity for life on sea and land. The tolerance of P. schlosseri to environmental ammonia is much higher than any other fishes because of its capability to actively excrete NH4 + and its low skin permeability to NH4 + , which prevents back diffusion [115]. In this context, the amino groups of these AAs are transferred directly or indirectly to pyruvate to form alanine. The carbon chains are fed into the TCA cycle and are partially oxidized to malate, which could replenish pyruvate through the function of the malic enzyme. This favorable ATP yield from partial AA catabolism is not accompanied by a net release of ammonia [114]. Mudskippers can be very active on land. Thus, urea formation, which is energetically expensive, may not be a suitable strategy. By exposing mudskippers to terrestrial conditions, in constant darkness to minimize physical activity, the researchers reduced the rate of proteolysis and AA catabolism in response to aerial exposure [116]. In contrast, increased concentrations of alanine, BCAAs, and total free AAs were observed in the tissues of P. schlosseri exposed to terrestrial conditions for 24 h [117].

Proteins are one of the primary sources of metabolic energy in carnivorous fishes. The main storage tissue of utilizable protein is white muscle. AAs released through proteolysis can be oxidized either as energy or converted to other utilizable forms via anabolic pathways, as noted previously [11,14]. Before AAs can be oxidized through the TCA cycle, the amino group must be removed by either transamination or deamination. Ammonia is not produced during transamination, but deamination produces either NH3, which spontaneously takes up H + to form NH4 + [118]. Certain AAs (e.g. arginine, glutamine, histidine, and proline) can be converted to glutamate, which can undergo deamination by glutamate dehydrogenase, producing NH4 + and α-ketoglutarate. The latter is fed into the TCA cycle. Glutamate can also undergo transamination with pyruvate, catalyzed by alanine aminotransferase, producing α-ketoglutarate without releasing ammonia. Continuous glutamate-pyruvate transamination would facilitate the oxidation of the carbon chains of some AAs. Under normal circumstances, the carbon chain of an AA is completely oxidized to CO2 through the TCA cycle and the electron transport chain, thus producing ATP and/or its equivalent [119]. This would cause a reduction in the efficiency of ATP production because not all AAs would fully be oxidized, allowing certain AAs to be used as energy sources, while minimizing ammonia accumulation. In fish, alanine constitutes 20 to 30% of the total AA pool [119]. Most of the free AAs could be converted into alanine and the overall quantitative energetics would appear to be quite favorable. The net conversion of glutamate to alanine would yield 20 moles of ATP per mole of alanine formed if the resultant α-ketoglutarate is completely oxidized to CO2. This favorable ATP yield from AA catabolism is accompanied by a direct release of ammonia into the living environment.

Alanine is an important substrate for hepatic gluconeogenesis and is one of the main AAs released by the skeletal muscle [1]. It is also an important source of energy for fish. However, the effect of adding alanine into diets is controversial, as dietary alanine is largely extracted by the splanchnic bed. In addition, β-alanine supplementation does not affect the growth of Japanese flounder (Paralichthys olivaceus) [120].

Skeletal muscle plays an important role in initiating BCAA degradation via transamination. There are reports that muscle tissues of goldfish [121] and trout [122] have higher activities of BCAA transaminases than mammalian muscles, which indicates a high capacity for leucine catabolism in fish muscle. In trout, the rate of leucine catabolism is higher during intense swimming than at rest [40]. The quantitative importance of leucine oxidation by fish muscle depends mainly on the use of protein as an endogenous energy source, since blood leucine does not contribute significantly to total CO2 production. This means that other substrates (e.g., glutamate, glutamine, alanine and aspartate) contribute predominantly to ATP production during exercise in fish. The oxidation of alanine occurs within the muscle, kidney and liver via glutamate-pyruvate transaminase. Alanine transport into the cells is under hormonal control during stressful conditions. Thereby, alanine is actively released at high rates by all muscle types studied, ensuring its supply to the liver and kidneys and this AA may be a major final product of muscle metabolism [40].

Important Amino Acids as Energy Sources

The effects of synthetic methionine and lysine on the growth and feed conversion of animals are so impressive that the use of these two AA as feed additives worldwide exceeds 700,000 metric tons annually [123,124]. Lys has a particular role in metabolism, since Lys and Leu are exclusively ketogenic AAs that are broken down to acetyl-CoA, which is oxidized to CO2 via in the TCA cycle. Unlike Lys, Met is a glucogenic AA that produces glucose as an energy source. Under methionine-limiting conditions, excesses of branched-chain AAs reduce methionine oxidation possibly due to competitive inhibition by the branched-chain ketoacids. Through the formation of S-adenosylmethionine (a donor of methyl group), methionine plays a key role in one-carbon metabolism [45,46].

The transamination of non-essential AAs, such as alanine and aspartate, was found to be important for ATP production in fish in early investigations [71]. Alanine can stimulate the feeding response of certain fish [125] and carries nitrogen for inter-organ AA metabolism [36]. Recently, a study suggested a possible role for the hormones STC1 (a stanniocalcin homologue) and PTHrP (parathyroid hormone-relate protein) in teleost fish to safeguard liver glycogen reserves under stressful situations [126]. The strategy may involve the production of glucose via BCAA, alanine, glutamine, and glutamate and their mobilization from the muscle to the liver. Alanine is a fundamental AA that provides energy for the central nervous system during the starvation period by constant translocation from the muscle tissues through the blood system to the liver. However, under non-stressful conditions, the main energy source mainly comes from glutamate and glutamine [11].

Glycine participates in gluconeogenesis, sulfur AA metabolism, one-carbon metabolism, and fat digestion [127]. It also stimulates feed intake in many fish [125]. In sturgeon, increased levels of glycine and a reduction of glucogenic AAs occur in response to feed deprivation. Glycine represents almost 30% of collagen, the major structural protein of connective tissues, such as tendons, skin, and ligaments [128]. Moreover, glycine might be reserved for the synthesis of creatine and, thus, the generation of creatine phosphate, a high-energy molecule used as an energy source for overcoming extreme conditions, like running away from predators [129]. In this regard, glycine plays an important role in energy metabolism during periods of feed deprivation and for activities requiring rapid use of high quantities of energy.

Arginine is classified as an essential AA in young animals, including young fish, and is necessary for optimal growth [2]. Arginine plays various physiological roles in animal cells, such as serving as a component of proteins, an oxidative energy substrate, a stimulator of hormone secretion (e.g. growth hormone, insulin, glucagon), and a precursor of polyamine and nitric oxide (NO), which is vital for the vasodilation and immune responses [130]. In most mammals (e.g., humans, pigs and rat), the small intestine is the site for endogenous synthesis of citrulline and arginine from glutamine, glutamate and proline [21]. However, endogenous synthesis of arginine has not been demonstrated in most teleost fish [131]. In mammalian liver, arginine is essentially catabolized by arginase via the urea cycle [21]. The embryos of salmonids seem to have a functional urea cycle for ammonia detoxification, as researchers observed relatively higher activity of five urea cycle enzymes. This situation is quite different from adult fish. Arginase is ubiquitous in fish tissues, with the highest activity in the liver and kidney [132]. The dietary requirement for arginine among various fish species may differ because of differences in metabolic and enzymatic efficiency [131]. Previous growth studies suggested that the fish arginine requirement might range from 4 to 6% of dietary protein. Salmon have the highest requirement (about 6% of dietary protein), whereas this number ranges from 4 to 5% in other species [2]. Arginine is a nutritionally essential AA for fish not only as a precursor for protein synthesis, but also for its metabolic role in the production of diverse metabolites, including nitric oxide (NO), polyamines, urea, proline, and glutamate [130,133].

To improve the knowledge about the use of AAs as a major energy source in fish, it is important to understand the bioavailability of each dietary AA to be absorbed and retained. The estimated bioavailability of AAs could be indirectly determined by the digestibility of dietary proteins. However, in aquatic organisms, leaching of water-soluble nutrients from both feed and feces is always a factor contributing to inaccuracy when determining the amounts of available AAs that are actually absorbed. Apart from those AAs retained for anabolic processes (i.e. protein deposition during growth), there is also a need to determine the amounts required to meet the demands of metabolic processes. Therefore, the amounts of dietary AAs that enter the portal circulation cannot be determined precisely. It is important to distinguish those AAs used in metabolic processes (e.g., ATP production) from those retained by fish under starvation conditions. Clearly, more research is needed on the metabolism of AAs in swimming fish to solve this intriguing problem. Muscular performance depends critically on the adequate supply of metabolic fuels and disposal of final products. Therefore, knowing how metabolite fluxes are regulated is necessary to understand the strategies whereby fish survive, grow, and develop. The ATP used for contraction can be generated through various pathways of energy metabolism that catabolize carbohydrates, lipids, or proteins. It can be suggested that under both fed and food-deprived conditions, AAs are major metabolic fuels for the intestine, liver, skeletal muscle, kidneys, and possibly other tissues.

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    Received: October 08, 2020
    Accepted: October 17, 2020
    Published: October 25, 2020

    Francesca Falco, Paolo Stincone, Matteo Cammarata, Adriano Brandelli (2020) Amino Acids as the Main Energy Source in Fish Tissues. Aquac Fish Stud Volume 3(1): 1-11. DOI: 10.31038/AFS.2020223

    Examples of Catabolism

    Carbohydrate and Lipid Catabolism

    Almost all organisms use the sugar glucose as a source of energy and carbon chains. Glucose is stored by organisms in larger molecules called polysaccharides. These polysaccharides can be starches, glycogen, or other simple sugars like sucrose. When an animal’s cells need energy, it sends signals to the parts of the body that store glucose, or it consumes food. Glucose is released from the carbohydrates by special enzymes, in the first part of the catabolism. The glucose is then distributed into the body, for other cells to use as energy. The catabolic pathway glycolysis then breaks glucose down even further, releasing energy that is stored in ATP. From glucose, pyruvate molecules are made. Further catabolic pathways create acetate, which is a key metabolic intermediate molecule. Acetate can become a wide variety of molecules, from phospholipids, to pigment molecules, to hormones and vitamins.

    Fats, which are large lipid molecules, are also degraded by the metabolism to produce energy and to create other molecules. Similar to carbohydrates, lipids are stored in large molecules, but can be broken down into individual fatty acids. These fatty acids are then converted through beta-oxidation into acetate. Again, acetate can be used by the anabolism, to produce larger molecules, or as part of the citric acid cycle which drives respiration and ATP production. Animals use fats to store large amount of energy for future use. Unlike starches and carbohydrates, lipids are hydrophobic, and exclude water. In this way, a lot of energy can be stored without the heavy weight of water slowing the organism down.

    Most catabolic pathway are convergent in that they end in the same molecule. This enables organisms to consume and store energy in a variety of different forms, while still being able produce all the molecules it needs in the anabolic pathways. Other catabolic pathways, such as protein catabolism discussed below, create different intermediate molecules are precursors, known as amino acids, to build new proteins.

    Protein Catabolism

    If no source of glucose is present, or there are too many amino acids, the molecules will enter further catabolic pathways to be broken down into carbon skeletons. These small molecules can be combined in gluconeogenesis to create new glucose, which the cells can use as energy or store in large molecules. During starvation, cellular proteins can go through the catabolism to allow an organism to survive on its own tissues until more food is found. In this way, organisms can live with only small amounts of water for extremely long times. This makes them much more resilient to changing environmental conditions.

    NCERT Solutions for Class 11 Biology Chapter 9 Biomolecules

    These Solutions are part of NCERT Solutions for Class 11 Biology. Here we have given NCERT Solutions for Class 11 Biology Chapter 9 Biomolecules.

    Question 1.
    What are macromolecules? Give examples.
    Biomolecules i.e. chemical compounds found in living organisms are of two types. One, those which have molecular weights less than one thousand and are usually referred to as macromolecules or simply as biomolecules while those which are found in the acid-insoluble fraction are called macromolecules or as biomacromolecules.

    The molecules in the insoluble fraction with the exception of lipids are polymeric substances. Then why do lipids, whose molecular weights do not exceed 800, come under acid-insoluble fractions i.e., macromolecular fractions?

    Question 2.
    Illustrate a glycosidic, peptide and a phospho-diester bond.
    (a) Glycosidic bond: It is a bond formed between two monosaccharide molecules in a polysaccharide. This bond is formed between two carbon atoms of two adjacent monosaccharides.

    (b) Peptide bond: Amino acids are linked by a peptide bond which is between the carboxyl (- COOH) group of one amino acid and the amino (- NH 2 ) group of the next amino acid which is formed by the dehydration process.

    (c) Phosphodiester bond: This is the bond present between the phosphate and hydroxyl group of sugar which is called an ester bond. As this ester bond is present on either side, it is called a phosphodiester bond.

    Question 3.
    What is meant by the tertiary structure of proteins?
    Tertiary structure of protein : When the individual peptide chains of secondary structure of protein are further extensively coiled and folded into sphere-like shapes with the hydrogen bonds between the amino and carboxyl group and various other kinds of bonds cross-linking on-chain to another they form tertiary structure. The ability of proteins to carry out specific reactions is the result of their primary, secondary and tertiary structure.

    Question 4.
    Find and write down structures of 10 interesting small molecular weight biomolecules. Find if there is any industry which manufactures the compounds by isolation. Find out who are the buyers?

    Fat is being manufactured by many companies in pharmaceuticals business as well as in food business. Vitamins come in many combination and are being used as supplementary medicines. Lactose is made by companies in manufacturing baby food. All of us are buyers of fat, protein and lactose.

    Question 5.
    Proteins have primary structures. If you are given a method to know which amino acid is at either of two termini (ends) of a protein, can you connect this information to purity or homogeneity of a protein?
    The primary structure of proteins is described as the type, number, and order of amino acids in the chain. A protein is imagined as a line whose left end represents the first and right end represents the last amino acid. But in fact, this is not so simple. Actually, the number of amino acids in between the two termini determines the purity or homogeneity of a protein.

    Question 6.
    Find out and make a list of proteins used as therapeutic agents. Find other applications of proteins (e.g., Cosmetics, etc.)
    Haemoglobin, Insulin, thyroxine, growth hormone, other hormones of the adenohypophysis, serum albumen, serum globulin, fibrinogen, etc. are used as the therapeutic agents. Proteins are also used for the synthesis of food supplements, film, paint, plastic, etc.

    Question 7.
    Explain the composition of triglyceride.
    Triglycerides are esters of three molecules of fatty acids and one molecule of glycerol.

    Question 8.
    Can you describe what happens when milk is converted into curd or yoghurt, from your understanding of proteins.
    Conversion of milk into curd is the digestion of milk protein casein. Semi digested milk is the curd. In the stomach, renin converts milk protein into paracasein which then reacts with Ca ++ ion to form calcium paracaseinate which is called the curd or yoghurt.

    Question 9.
    Can you attempt building models of biomolecules using commercially available atomic models (Ball and Stick model)?
    Yes, the Three-dimensional structure of cellulose can be made using balls and sticks. Similarly, models of other bimolecular can be made

    Question 10.
    Attempt titrating an amino acid against a weak base and discover the number of dissociating (ionizable) functional groups in the amino acid.
    When an amino acid is titrated with weak base then its-COOH group also acts as weak acid. So it forms a salt with weak base then the pH of the resulting solution is near 7, so there is no sudden change. Number of dissociating functional groups are two, one is amino group (NH2) and another is carboxylic group ( – COOH). In the titration, amino acid acts as an indicator. Amino acids in solution acts as basic or acidic as situation demands. So these are also called amphipathic molecules.

    Question 11.
    Draw the structure of the amino acid, alanine.

    Question 12.
    What are gums made of? Is fevicol different?
    Gums are categorized into secondary metabolites or biomolecules. Thousands of compounds one present in plant-fungal and microbial cells. They are derived from these things. But is different. Fevicol has not derived from paper written cells.

    Question 13.
    Find out a qualitative test for proteins, fats and oils, amino acid and test any fruit juice, saliva, sweat and urine for them.
    Qualitative Tests for proteins, amino acids, and fats:
    Biuret Test: Biuret test for protein identifies the presence of protein by producing violet colour of solution. Biuret H2NCONHCONH2 reacts with copper ion in a basic solution and gives violet colour.
    Liebermann-Burchard Test for cholesterol:
    This is a mixture of acidic anhydride and sulphuric acid. This gives a green colour when mixed with cholesterol.
    Grease Test for oil: Certain oils give a translucent stain on clothes. This tesi can be used to show presence of fat in vegetable oils. These tests can be performed to check presence of proteins and amino acids and fats in any of the fluid mentioned in the question.

    Question 14.
    Find out how much cellulose is made by all the plants in the biosphere and compare it with how much of paper is manufactured by man and hence what is the consumption of plant material by man annually. What a loss of vegetation?
    According to a 2006 report from the UN, forests store about 312 billion tons of carbon in their biomass alone. If you add to that the carbon in deadwood, litter, and forest soil, the figure increases to about 1.1 trillion tons! The UN assessment also shows that the destruction of forests adds almost 2.2 billion tons of carbon to the atmosphere each year, the equivalent of what the U.S. emits annually. Many climate experts believe that the preservation and restoration of forests offers one of the least expensive and best ways to fight against climate change.
    Although it is difficult to get exact data about the quantum of cellulose produced by plants, but above information can give some idea. About 10% of cellulose is used in paper making. The percentage is less but wrong practice of cutting wood and re-plantation makes the problem complicated. Usually older trees are cut for large quantity of cellulose and re-plantation is limited to selected species of plants. Selected species disturb the biodiversity as it leads to monoculture.
    Add to this the problem of effluents coming out of a paper factory and the problem further aggravates.

    Question 15.
    Describe the important properties of enzymes.
    Properties of enzymes

    • Enzyme catalysis hydrolysis of ester, ether, peptide, c-c, c-halids, or P-N bonds.
    • Enzymes catalysis removal of the group from the substrate by mechanisms other than hydrolysis of leaving double bonds.
    • Enzymes generally function in a narrow range of temperature and p H .
    • Activity declines both below and above optimum temperature and p H .
    • The higher the affinity of the enzyme for its substrate the greater is its catalytic activity.
    • The activity of an enzyme is also sensitive to the presence of specific chemicals that bind to the enzyme.
    • For eg: Inhibitors that shuts off enzyme activity and Co-factors that facilitate catalytic activity.
    • Enzymes retain their identity at the end of the reaction.


    Question 1.
    Which organic compound is commonly called animal starch?

    Question 2.
    Name the biomolecules of life.
    Carbohydrates, Lipids, Proteins, Enzymes, and nucleic acids.

    Question 3.
    Name one basic amino acid.

    Question 4.
    Name one heteropolysaccharide.

    Question 5.
    Name the biomolecules present in the acid-insoluble fraction.
    Protein, polysaccharide, nucleic acid, and lipids.

    Question 6.
    Name the bond formed between sugar molecules.
    Glycosidic bond.

    Question 7.
    Name three pyrimidines.
    Thymine, cytosine, and uracil

    Question 8.
    Which enzyme does catalyse covalent bonding between two molecules to form a large molecule?

    Question 9.
    On reaction with iodine, starch turns blue-black, why?
    The appearance of blue colour with the addition of iodine is due to its reaction with amylose fraction of starch.

    Question 10.
    Which type of bonds are found in proteins and polysaccharides?
    Peptides bond in protein and glycosidic bonds in polysaccharides.

    Question 11.
    Name one neutral amino acid.

    Question 12.
    Where does histone occur?

    Question 13.
    Name two different kinds of metabolism.
    Anabolism and catabolism.


    Question 1.
    Which type of bonds are found in nucleic acids?
    Phosphodiester bond.

    Question 2.
    What are the monosaccharides present in DNA and RNA? (Chikmagalur 2004)
    Deoxyribose in DNA and Ribose in RNA.

    Question 3.
    What are fatty acids? Give two examples.
    Fatty acids are compounds which have a carboxyl group attached to an R-group, which could be a methyl (CH3), or ethyl (C2H5) group or a higher number of CH2 groups e.g., Linoleic acid, Palmitic acid.

    Question 4.
    What are co-enzymes? Give two examples.
    Coenzymes are the non-protein organic ^compounds bound to the apoenzyme in a conjugate enzyme, their association with the apoenzyme is only transient, e.g., Nicotinamide adenine dinucleotide (NAD). Flavin adenine dinucleotide (FAD), Nicotinamide adenine dinucleotide phosphate (NADP).

    Question 5.
    (i) What is meant by complementary base pairing?
    (ii) What is the distance between two successive bases in a strand of DNA?
    (iii) How many base pairs are present in one turn of the helix of a DNA strand?
    (i) Complementary base pairing is the type of
    pairing in DNA, where a purine always pairs with a pyrimidine, i.e., adenine pairs with thymine (A=T) and guanine pairs with cytosine (G=C).
    (ii) 0.34 nm or 34 A is the distance between two successive bases in the strand of DNA
    (iii) 10 base pairs

    Question 6.
    Differentiate between DNA and RNA.
    The main differences between DNA add RNA are as following

    Question 7.
    What la a prosthetic group? Give an example.
    The non-protein part of a conjugated protein is called a prosthetic group. For example in a nucleoprotein (nucleic acid is the prosthetic group).

    Question 8.
    Differentiate between essential amino acids and non-essential amino acids.

    Question 9.
    Differentiate between Structural Proteins and Functional Proteins.

    Question 10.
    What is activation energy?
    Activation Energy: An energy barrier is required for the reactant molecules for their activation. So this energy with enzyme-substrate reaction is called Activation energy.

    The activation energy is low for reactions with catalysts [enzymes] than those with Non enzymatic reactions.

    Question 11.
    What are the components of enzymes?
    Enzymes are made up of protein as well as non – protein parts. The protein part is called an apoenzyme and the non-protein part is a coenzyme. These two together are called a holoenzyme.


    Question 1.
    How many classes are enzymes divided into? Name all the classes.
    Enzymes are divided into 6 classes. Namely

    1. Oxidoreductases/dehydrogenases: Enzymes which catalyze oxidoreduction between two substrates
    2. Transferases: Enzymes catalyzing a transfer of group between a pair of substrates.
    3. Hydrolases: Enzymes catalyzing the hydrolysis of ester, ether, peptide, glycosidic, C-C-C-halide or P.N bonds.
    4. Lyases: Enzymes catalyze the removal of groups from – substrates by mechanisms other than hydrolysis leaving double bonds.
    5. Lyases: Enzymes catalyzing the interconversion of optical geometric or positional isomers.
    6. Ligases: Enzymes catalyzing the linking together of 2 compounds.

    Question 2.
    Distinguish between the primary, secondary, and tertiary structures of proteins.

    Question 3.
    Explain the effect of the following factors on enzyme activity:
    (i) Temperature
    (ii) pH.
    Temperature: An enzyme is active within a narrow range of temperature. The temperature at which an enzyme shows its highest activity is called optimum temperature.

    It generally corresponds to the body temperature of warm blood animals e.g., 37°C in human beings. Enzyme activity decreases above and below this temperature. Enzyme becomes inactive below minimum temperature and beyond maximum temperature.

    Low temperature present inside cold storage prevents spoilage of food. High temperature destroys enzymes by causing their denaturation.

    The relation between temperature and enzyme controlled reaction velocity

    pH – Every enzyme has an optimum pH when it is most effective.

    A rise or fall in pH reduces enzyme activity by changing the degree of ionisation of its side chains. A change in pH may also reverse the reaction.

    Most of the intracellular enzymes function near-neutral pH with the exception of several digestive enzymes which work either in acidic range of pH or alkaline range of pH. pH for trypsin is 8.5.

    Question 4.
    Discuss the B-DNA helical structure with the help of a diagram.

    • Watson & Crick suggested the double-helical structure of DNA in 1953.
    • The backbone of the DNA molecule is made up of deoxyribonucleotide units joined by a phosphodiester bond.
    • The DNA molecule consists of two chains wrapped around each other.
    • The two helical strands are bound to each other by Hydrogen Bonds.
    • Purines bind with pyrimidines A = T, C = G
    • The pairing is specific and the two chains are complementary.
    • One strand has the orientation 5’ → 3’ and other has 3’ → 5’.
    • Both polynucleotides strands remain separated with a 20A° distance.
    • The coiling is right-handed.

    Question 5.
    What are different kinds of enzymes? Mention with enzyme examples.
    Enzymes with substrate bonds are broken and changed to different kinds as

    1. Oxidoreductases: eg Alcohol dehydrogenase, oxidation, Reduction occurs
    2. Transferases: transfer a particular group to another substrate, eg. transavninase
    3. Hydrolases: cleave their substrates by hydrolysis of a covalent bond e.g. Urease, amylase.
    4. Lyases: break the covalent bond eg. Deaminase
    5. Isomerase: by changing the bonds they make isomers. eg: Aldolase.
    6. Ligase: These bind two substrate molecules eg: DNA ligase, RNA ligase

    We hope the NCERT Solutions for Class 11 Biology at Work Chapter 9 Biomolecules, help you. If you have any query regarding NCERT Solutions for Class 11 Biology at Work Chapter 9 Biomolecules, drop a comment below and we will get back to you at the earliest.

    Purine and Pyrimidine Metabolism

    One of the important specialized pathways of a number of amino acids is the synthesis of purine and pyrimidine nucleotides. These nucleotides are important for a number of reasons. Most of them, not just ATP, are the sources of energy that drive most of our reactions. ATP is the most commonly used source but GTP is used in protein synthesis as well as a few other reactions. UTP is the source of energy for activating glucose and galactose. CTP is an energy source in lipid metabolism. AMP is part of the structure of some of the coenzymes like NAD and Coenzyme A. And, of course, the nucleotides are part of nucleic acids. Neither the bases nor the nucleotides are required dietary components. (Another perspective on this.) We can both synthesize them de novo and salvage and reuse those we already have.


    Nitrogen Bases

    There are two kinds of nitrogen-containing bases - purines and pyrimidines. Purines consist of a six-membered and a five-membered nitrogen-containing ring, fused together. Pyridmidines have only a six-membered nitrogen-containing ring. There are 4 purines and 4 pyrimidines that are of concern to us.


    • Adenine = 6-amino purine
    • Guanine = 2-amino-6-oxy purine
    • Hypoxanthine = 6-oxy purine
    • Xanthine = 2,6-dioxy purine

    Adenine and guanine are found in both DNA and RNA. Hypoxanthine and xanthine are not incorporated into the nucleic acids as they are being synthesized but are important intermediates in the synthesis and degradation of the purine nucleotides.


    • Uracil = 2,4-dioxy pyrimidine
    • Thymine = 2,4-dioxy-5-methyl pyrimidine
    • Cytosine = 2-oxy-4-amino pyrimidine
    • Orotic acid = 2,4-dioxy-6-carboxy pyrimidine

    Cytosine is found in both DNA and RNA. Uracil is found only in RNA. Thymine is normally found in DNA. Sometimes tRNA will contain some thymine as well as uracil.


    If a sugar, either ribose or 2-deoxyribose , is added to a nitrogen base, the resulting compound is called a nucleoside . Carbon 1 of the sugar is attached to nitrogen 9 of a purine base or to nitrogen 1 of a pyrimidine base. The names of purine nucleosides end in -osine and the names of pyrimidine nucleosides end in -idine. The convention is to number the ring atoms of the base normally and to use l', etc. to distinguish the ring atoms of the sugar. Unless otherwise specificed, the sugar is assumed to be ribose. To indicate that the sugar is 2'-deoxyribose, a d- is placed before the name.

    • Adenosine
    • Guanosine
    • Inosine - the base in inosine is hypoxanthine
    • Uridine
    • Thymidine
    • Cytidine


    Adding one or more phosphates to the sugar portion of a nucleoside results in a nucleotide . Generally, the phosphate is in ester linkage to carbon 5' of the sugar. If more than one phosphate is present, they are generally in acid anhydride linkages to each other. If such is the case, no position designation in the name is required. If the phosphate is in any other position, however, the position must be designated. For example, 3'-5' cAMP indicates that a phosphate is in ester linkage to both the 3' and 5' hydroxyl groups of an adenosine molecule and forms a cyclic structure. 2'-GMP would indicate that a phosphate is in ester linkage to the 2' hydroxyl group of a guanosine. Some representative names are:

    • AMP = adenosine monophosphate = adenylic acid
    • CDP = cytidine diphosphate
    • dGTP = deoxy guanosine triphosphate
    • dTTP = deoxy thymidine triphosphate (more commonly designated TTP)
    • cAMP = 3'-5' cyclic adenosine monophosphate


    Nucleotides are joined together by 3'-5' phosphodiester bonds to form polynucleotides. Polymerization of ribonucleotides will produce an RNA while polymerization of deoxyribonucleotides leads to DNA.

    Hydrolysis of Polynucleotides

    Most, but not all, nucleic acids in the cell are associated with protein. Dietary nucleoprotein is degraded by pancreatic enzymes and tissue nucleoprotein by lysosomal enzymes. After dissociation of the protein and nucleic acid, the protein is metabolized like any other protein.

    The nucleic acids are hydrolyzed randomly by nucleases to yield a mixture of polynucleotides. These are further cleaved by phosphodiesterases (exonucleases) to a mixture of the mononucleotides. The specificity of the pancreatic nucleotidases gives the 3'-nucleotides and that of the lysosomal nucleotidases gives the biologically important 5'-nucleotides.

    The nucleotides are hydrolyzed by nucleotidases to give the nucleosides and P i . This is probably the end product in the intestine with the nucleosides being the primary form absorbed. In at least some tissues, the nucleosides undergo phosphorolysis with nucleoside phosphorylases to yield the base and ribose 1-P (or deoxyribose 1-P). Since R 1-P and R 5-P are in equilibrium, the sugar phosphate can either be reincorporated into nucleotides or metabolized via the Hexose Monophosphate Pathway. The purine and pyrimidine bases released are either degraded or salvaged for reincorporation into nucleotides. There is significant turnover of all kinds of RNA as well as the nucleotide pool. DNA doesn't turnover but portions of the molecule are excised as part of a repair process.

    Purine and pyrimidines from tissue turnover which are not salvaged are catabolized and excreted. Little dietary purine is used and that which is absorbed is largely catabolized as well. Catabolism of purines and pyrimidines occurs in a less useful fashion than did the catabolism of amino acids in that we do not derive any significant amount of energy from the catabolism of purines and pyrimidines. Pyrimidine catabolism, however, does produce beta-alanine, and the endproduct of purine catabolism, which is uric acid in man, may serve as a scavenger of reactive oxygen species.

    Purine Catabolism

    Nucleotides to Bases

    Guanine nucleotides are hydrolyzed to the nucleoside guanosine which undergoes phosphorolysis to guanine and ribose 1-P . Man's intracellular nucleotidases are not very active toward AMP, however. Rather, AMP is deaminated by the enzyme adenylate (AMP) deaminase to IMP . In the catobilsm of purine nucleotides, IMP is further degraded by hydrolysis with nucleotidase to inosine and then phosphorolysis to hypoxanthine .

    Adenosine does occur but usually arises from S-Adenosylmethionine during the course of transmethylation reactions. Adenosine is deaminated to inosine by an adenosine deaminase. Deficiencies in either adenosine deaminase or in the purine nucleoside phosphorylase lead to two different immunodeficiency diseases by mechanisms that are not clearly understood. With adenosine deaminase deficiency , both T and B-cell immunity is affected. The phosphorylase deficiency affects the T cells but B cells are normal. In September, 1990, a 4 year old girl was treated for adenosine deaminase deficiency by genetically engineering her cells to incorporate the gene. The treatment,so far, seems to be successful.

    Whether or not methylated purines are catabolized depends upon the location of the methyl group. If the methyl is on an -NH 2 , it is removed along with the -NH 2 and the core is metabolized in the usual fashion. If the methyl is on a ring nitrogen, the compound is excreted unchanged in the urine.

    Bases to Uric Acid

    Both adenine and guanine nucleotides converge at the common intermediate xanthine . Hypoxanthine, representing the original adenine, is oxidized to xanthine by the enzyme xanthine oxidase . Guanine is deaminated, with the amino group released as ammonia, to xanthine. If this process is occurring in tissues other than liver, most of the ammonia will be transported to the liver as glutamine for ultimate excretion as urea.

    Xanthine, like hypoxanthine, is oxidized by oxygen and xanthine oxidase with the production of hydrogen peroxide. In man, the urate is excreted and the hydrogen peroxide is degraded by catalase. Xanthine oxidase is present in significant concentration only in liver and intestine. The pathway to the nucleosides, possibly to the free bases, is present in many tissues.

    Gouts and Hyperuricemia

    Both undissociated uric acid and the monosodium salt (primary form in blood) are only sparingly soluble. The limited solubility is not ordinarily a problem in urine unless the urine is very acid or has high [Ca 2+ ]. [Urate salts coprecipitate with calcium salts and can form stones in kidney or bladder.] A very high concentration of urate in the blood leads to a fairly common group of diseases referred to as gout. The incidence of gout in this country is about 3/1000.

    Gout is a group of pathological conditions associated with markedly elevated levels of urate in the blood (3-7 mg/dl normal). Hyperuricemia is not always symptomatic, but, in certain individuals, something triggers the deposition of sodium urate crystals in joints and tissues. In addition to the extreme pain accompanying acute attacks, repeated attacks lead to destruction of tissues and severe arthritic-like malformations. The term gout should be restricted to hyperuricemia with the presence of these tophaceous deposits.

    Urate in the blood could accumulate either through an overproduction and/or an underexcretion of uric acid. In gouts caused by an overproduction of uric acid, the defects are in the control mechanisms governing the production of - not uric acid itself - but of the nucleotide precursors. The only major control of urate production that we know so far is the availability of substrates (nucleotides, nucleosides or free bases) .

    One approach to the treatment of gout is the drug allopurinol , an isomer of hypoxanthine.

    Allopurinol is a substrate for xanthine oxidase, but the product binds so tightly that the enzyme is now unable to oxidized its normal substrate. Uric acid production is diminished and xanthine and hypoxanthine levels in the blood rise. These are more soluble than urate and are less likely to deposit as crystals in the joints. Another approach is to stimulate the secretion of urate in the urine.


    In summary, all, except ring-methylated, purines are deaminated (with the amino group contributing to the general ammonia pool) and the rings oxidized to uric acid for excretion. Since the purine ring is excreted intact, no energy benefit accrues to man from these carbons.

    Pyrimidine Catabolism

    Ring Cleavage

    In order for the rings to be cleaved, they must first be reduced by NADPH . Atoms 2 and 3 of both rings are released as ammonia and carbon dioxide. The rest of the ring is left as a beta-amino acid . Beta-amino isobutyrate from thymine or 5-methyl cytosine is largely excreted. Beta-alanine from cytosine or uracil may either be excreted or incorporated into the brain and muscle dipeptides, carnosine (his-beta-ala) or anserine (methyl his-beta-ala).

    General Comments

    Purine and pyrimidine bases which are not degraded are recycled - i.e. reincorporated into nucleotides. This recycling, however, is not sufficient to meet total body requirements and so some de novo synthesis is essential. There are definite tissue differences in the ability to carry out de novo synthesis. De novo synthesis of purines is most active in liver. Non-hepatic tissues generally have limited or even no de novo synthesis. Pyrimidine synthesis occurs in a variety of tissues. For purines, especially, non-hepatic tissues rely heavily on preformed bases - those salvaged from their own intracellular turnover supplemented by bases synthesized in the liver and delivered to tissues via the blood.

    "Salvage" of purines is reasonable in most cells because xanthine oxidase, the key enzyme in taking the purines all of the way to uric acid, is significantly active only in liver and intestine. The bases generated by turnover in non-hepatic tissues are not readily degraded to uric acid in those tissues and, therefore, are available for salvage. The liver probably does less salvage but is very active in de novo synthesis - not so much for itself but to help supply the peripheral tissues.

    De novo synthesis of both purine and pyrimidine nucleotides occurs from readily available components.

    We use for purine nucleotides the entire glycine molecule (atoms 4, 5,7), the amino nitrogen of aspartate (atom 1), amide nitrogen of glutamine (atoms 3, 9), components of the folate-one-carbon pool(atoms 2, 8), carbon dioxide, ribose 5-P from glucose and a great deal of energy in the form of ATP. In de novo synthesis, IMP is the first nucleotide formed. It is then converted to either AMP or GMP.

    Since the purines are synthesized as the ribonucleotides, (not as the free bases) a necessary prerequisite is the synthesis of the activated form of ribose 5-phosphate. Ribose 5-phosphate reacts with ATP to form 5-Phosphoribosyl-1-pyrophosphate (PRPP) .

    This reaction occurs in many tissues because PRPP has a number of roles - purine and pyrimidine nucleotide synthesis, salvage pathways, NAD and NADP formation. The enzyme is heavily controlled by a variety of compounds (di- and tri-phosphates, 2,3-DPG), presumably to try to match the synthesis of PRPP to a need for the products in which it ultimately appears.

    Commitment Step

    De novo purine nucleotide synthesis occurs actively in the cytosol of the liver where all of the necessary enzymes are present as a macro-molecular aggregate. The first step is a replacement of the pyrophosphate of PRPP by the amide group of glutamine. The product of this reaction is 5-Phosphoribosylamine . The amine group that has been placed on carbon 1 of the sugar becomes nitrogen 9 of the ultimate purine ring. This is the commitment and rate-limiting step of the pathway.

    The enzyme is under tight allosteric control by feedback inhibition. Either AMP, GMP, or IMP alone will inhibit the amidotransferase while AMP + GMP or AMP + IMP together act synergistically . This is a fine control and probably the major factor in minute by minute regulation of the enzyme. The nucleotides inhibit the enzyme by causing the small active molecules to aggregate to larger inactive molecules.

    [PRPP] also can play a role in regulating the rate. Normal intracellular concentrations of PRPP (which can and do fluctuate) are below the KM of the enzyme for PRPP so there is great potential for increasing the rate of the reaction by increasing the substrate concentration. The kinetics are sigmoidal. The enzyme is not particularly sensitive to changes in [Gln] (Kinetics are hyperbolic and [gln] approximates KM). Very high [PRPP] also overcomes the normal nucleotide feedback inhibition by causing the large, inactive aggregates to dissociate back to the small active molecules.

    Purine de novo synthesis is a complex, energy-expensive pathway. It should be, and is, carefully controlled.

    Formation of IMP

    Once the commitment step has produced the 5-phosphoribosyl amine, the rest of the molecule is formed by a series of additions to make first the 5- and then the 6-membered ring. (Note: the numbers given to the atoms are those of the completed purine ring and names, etc. of the intermediate compounds are not given.) The whole glycine molecule, at the expense of ATP adds to the amino group to provide what will eventually be atoms 4, 5, and 7 of the purine ring (The amino group of 5-phosphoribosyl amine becomes nitrogen N of the purine ring.) One more atom is needed to complete the five-membered ring portion and that is supplied as 5, 10-Methenyl tetrahydrofolate.

    Before ring closure occurs, however, the amide of glutamine adds to carbon 4 to start the six-membered ring portion (becomes nitrogen 3). This addition requires ATP. Another ATP is required to join carbon 8 and nitrogen 9 to form the five-membered ring.

    The next step is the addition of carbon dioxide (as a carboxyl group) to form carbon 6 of the ring. The amine group of aspartate adds to the carboxyl group with a subsequent removal of fumarate. The amino group is now nitrogen 1 of the final ring. This process, which is typical for the use of the amino group of aspartate, requires ATP. The final atom of the purine ring, carbon 2, is supplied by 10-Formyl tetrahydrofolate. Ring closure produces the purine nucleotide, IMP.

    Note that at least 4 ATPs are required in this part of the process. At no time do we have either a free base or a nucleotide.

    Formation of AMP and GMP

    IMP can then become either AMP or GMP. GMP formation requires that IMP be first oxidized to XMP using NAD. The oxygen at position 2 is substituted by the amide N of glutamine at the expense of ATP. Similarly, GTP provides the energy to convert IMP to AMP . The amino group is provided by aspartate in a mechanism similar to that used in forming nitrogen 1 of the ring. Removal of the carbons of aspartate as fumarate leaves the nitrigen behind as the 6-amino group of the adenine ring. The monophosphates are readily converted to the di- and tri-phosphates.

    Control of De Novo Synthesis

    Control of purine nucleotide synthesis has two phases. Control of the synthesis as a whole occurs at the amidotransferase step by nucleotide inhibition and/or [PRPP]. The second phase of control is involved with maintaining an appropriate balance (not equality) between ATP and GTP . Each one stimulates the synthesis of the other by providing the energy. Feedback inhibition also controls the branched portion as GMP inhibits the conversion of IMP to XMP and AMP inhibits the conversion of IMP to adenylosuccinate.

    One could imagine the controls operating in such a way that if only one of the two nucleotides were required, there would be a partial inhibition of de novo synthesis because of high levels of the other and the IMP synthesized would be directed toward the synthesis of the required nucleotide. If both nucleotides were present in adequate amounts, their synergistic effect on the amidotransferase would result in almost complete inhibition of de novo synthesis.

    De Novo Synthesis of Pyrimidine Nucleotides

    Since pyrimidine molecules are simpler than purines, so is their synthesis simpler but is still from readily available components. Glutamine's amide nitrogen and carbon dioxide provide atoms 2 and 3 or the pyrimidine ring. They do so, however, after first being converted to carbamoyl phosphate. The other four atoms of the ring are supplied by aspartate. As is true with purine nucleotides, the sugar phosphate portion of the molecule is supplied by PRPP.

    Carbamoyl Phosphate

    Pyrimidine synthesis begins with carbamoyl phosphate synthesized in the cytosol of those tissues capable of making pyrimidines (highest in spleen, thymus, GItract and testes). This uses a different enzyme than the one involved in urea synthesis. Carbamoyl phosphate synthetase II (CPS II) prefers glutamine to free ammonia and has no requirement for N-Acetylglutamate.

    Formation of Orotic Acid

    Carbamoyl phosphate condenses with aspartate in the presence of aspartate transcarbamylase to yield N-carbamylaspartate which is then converted to dihydroorotate.

    In man, CPSII, asp-transcarbamylase, and dihydroorotase activities are part of a multifunctional protein .

    Oxidation of the ring by a complex, poorly understood enzyme produces the free pyrimidine, orotic acid. This enzyme is located on the outer face of the inner mitochondrial membrane, in contrast to the other enzymes which are cytosolic. Note the contrast with purine synthesis in which a nucleotide is formed first while pyrimidines are first synthesized as the free base .

    Formation of the Nucleotides

    Orotic acid is converted to its nucleotide with PRPP. OMP is then converted sequentially - not in a branched pathway - to the other pyrimidine nucleotides. Decarboxylation of OMP gives UMP . O-PRT and OMP decarboxylase are also a multifunctional protein . After conversion of UMP to the triphosphate, the amide of glutamine is added, at the expense of ATP, to yield CTP .


    The control of pyrimidine nucleotide synthesis in man is exerted primarily at the level of cytoplasmic CPS II . UTP inhibits the enzyme, competitively with ATP. PRPP activates it. Other secondary sites of control also exist (e.g. OMP decarboxylase is inhibited by UMP and CMP). These are probably not very important under normal circumstances.

    In bacteria, aspartate transcarbamylase is the control enzyme. There is only one carbamoyl phosphate synthetase in bacteria since they do not have mitochondria. Carbamoyl phosphate, thus, participates in a branched pathway in these organisms that leads to either pyrimidine nucleotides or arginine.

    Interconversion of Nucleotides

    The monophosphates are the forms synthesized de novo although the triphosphates are the most commonly used forms. But, of course, the three forms are in equilibrium. There are several enzymes classified as nucleoside monophosphate kinases which catalyze the general reaction:(= represents a reversible reaction)

    Base-monophosphate + ATP = Base-diphosphate + ADP

    e.g. Adenylate kinase: AMP + ATP = 2 ADP

    There is a different enzyme for GMP, one for pyrimidines and also enzymes that recognize the deoxy forms.

    Similarly, the diphosphates are converted to the triphosphates by nucleoside diphosphate kinase :

    There may be only one nucleoside diphosphate kinase with broad specificity. One can legitimately speak of a pool of nucleotides in equilibrium with each other.

    Salvage of Bases

    Salvaging of purine and pyrimidine bases is an exceedingly important process for most tissues. There are two distinct pathways possible for salvaging the bases.

    Salvaging Purines

    The more important of the pathways for salvaging purines uses enzymes called phosphoribosyltransferases (PRT) :

    PRTs catalyze the addition of ribose 5-phosphate to the base from PRPP to yield a nucleotide.:

    Base + PRPP = Base-ribose-phosphate (BMP) + PPi

    We gave already seen one example of this type of enzyme as a normal part of de novo synthesis of the pyrimidine nucleotides, - O-PRT.

    As a salvage process though, we are dealing with purines. There are two enzymes, A-PRT and HG-PRT. A-PRT is not very important because we generate very little adenine. (Remember that the catabolism of adenine nucleotides and nucleosides is through inosine). HG-PRT , though, is exceptionally important and it is inhibited by both IMP and GMP. This enzyme salvages guanine directly and adenine indirectly. Remember that AMP is generated primarily from IMP, not from free adenine.

    Lesch-Nyhan Syndrome

    HG-PRT is deficient in the disease called Lesch-Nyhan Syndrome , a severe neurological disorder whose most blatant clinical manifestation is an uncontrollable self-mutilation. Lesch-Nyhan patients have very high blood uric acid levels because of an essentially uncontrolled de novo synthesis . (It can be as much as 20 times the normal rate). There is a significant increase in PRPP levels in various cells and an inability to maintain levels of IMP and GMP via salvage pathways. Both of these factors could lead to an increase in the activity of the amidotransferase.

    Salvaging Pyrimidines

    A second type of salvage pathway involves two steps and is the major pathway for the pyrimidines, uracil and thymine.

    Base + Ribose 1-phosphate = Nucleoside + Pi (nucleoside phosphorylase)

    Nucleoside + ATP - Nucleotide + ADP (nucleoside kinase - irreversible)

    There is a uridine phosphorylase and kinase and a deoxythymidine phosphorylase and a thymidine kinase which can salvage some thymine in the presence of dR 1-P.

    Formation of Deoxyribonucleotides

    De novo synthesis and most of the salvage pathways involve the ribonucleotides. (Exception is the small amount of salvage of thymine indicated above.) Deoxyribonucleotides for DNA synthesis are formed from the ribonucleotide diphosphates (in mammals and E. coli ).

    A base diphosphate (BDP) is reduced at the 2' position of the ribose portion using the protein, thioredoxin and the enzyme nucleoside diphosphate reductase . Thioredoxin has two sulfhydryl groups which are oxidized to a disulfide bond during the process. In order to restore the thioredoxin to its reduced for so that it can be reused, thioredoxin reductase and NADPH are required.

    This system is very tightly controlled by a variety of allosteric effectors. dATP is a general inhibitor for all substrates and ATP an activator. Each substrate then has a specific positive effector (a BTP or dBTP). The result is a maintenance of an appropriate balance of the deoxynucleotides for DNA synthesis.

    Synthesis of dTMP

    DNA synthesis also requires dTMP (dTTP). This is not synthesized in the de novo pathway and salvage is not adequate to maintain the necessary amount. dTMP is generated from dUMP using the folate-dependent one-carbon pool.

    Since the nucleoside diphosphate reductase is not very active toward UDP, CDP is reduced to dCDP which is converted to dCMP. This is then deaminated to form dUMP. In the presence of 5,10-Methylene tetrahydrofolate and the enzyme thymidylate synthetase , the carbon group is both transferred to the pyrimidine ring and further reduced to a methyl group. The other product is dihydrofolate which is subsequently reduced to the tetrahydrofolate by dihydrofolate reductase.

    Chemotherapeutic Agents

    Thymidylate synthetase is particularly sensitive to availability of the folate one-carbon pool. Some of the cancer chemotherapeutic agents interfere with this process as well as with the steps in purine nucleotide synthesis involving the pool.

    Cancer chemotherapeutic agents like methotrexate (4-amino, 10-methyl folic acid) and aminopterin (4-amino, folic acid) are structural analogs of folic acid and inhibit dihydrofolate reductase. This interferes with maintenance of the folate pool and thus of de novo synthesis of purine nucleotides and of dTMP synthesis. Such agents are highly toxic and administered under careful control.

    Quiz Questions

    If you would like to test your level of understanding, you may try these multiple choice quiz questions.

    Return to the NetBiochem Welcome page, where you can choose another topic.

    First up are the essential amino acids. These are the nine amino acids that your body cannot create on its own, and that you must obtain by eating various foods. Adults need to eat foods that contain the following eight amino acids: methionine, valine, tryptophan, isoleucine, leucine, lysine, threonine and phenylalanine. Histidine, the ninth amino acid, is only necessary for babies.

    Instead of storing up a supply of the essential acids, the body uses them to create new proteins on a regular basis. Therefore, the body needs a continual – ideally daily – supply of these amino acids to stay healthy.


    Food consumption data from the U.S. Department of Agriculture's (USDA) 1977� and 1985 surveys indicate that 14 to 18% of the total food energy intake is derived from protein (USDA, 1983, 1986, 1987). Despite wide variations in food energy intake, this proportion remains similar for both sexes and all age groups except infants. There is also little change as a function of household income, urbanization, or race. Food items likely to be underreported in surveys (e.g., alcoholic beverages, confections) would provide energy but little protein hence, the percentage of energy from protein may be overestimated. Average consumption levels are, however, quite generous: about 50 g/day in preschool children 70 to 85 g in older children 90 to 110 g in male and 65 to 70 g in female adolescents and adults and 75 to 80 g in men and 55 to 65 g in women over age 65.

    Foods of animal origin contribute approximately 65% of the protein in the USDA survey, with the proportion from the meat and dairy groups varying somewhat with age (USDA, 1983). Similarly, the data from the second National Health and Nutrition Examination Survey (NHANES II) indicate that about 48% of the protein is derived from meat, fish, and poultry 17% from dairy products and 4% from eggs (Block et al., 1985). The importance of grain products as suppliers of protein is not always realized, particularly in populations ingesting diets rich in animal products. Cereal grains supply an average of 16 to 20% of the total protein intake in the United States.

    The amino acid pattern in the diet consumed by children ages 1 to 3 years and all persons surveyed is given in Table 6-5. The pattern is uniform between the age groups and meets the requirement pattern levels for all age groups except infants. The U.S. consumption pattern also meets the provisional pattern for lactating women. Therefore, no adjustment to the recommended allowance for reference protein is required for people consuming a typical U.S. diet.

    Digestibility The amino acid score alone may lead to an overestimation of the capacity of some proteins to meet physiological requirements unless digestibility is taken into account. When the amino acid score is multiplied by digestibility, it becomes analogous to the biologically determined net protein utilization (NPU). The NPU is the product of biological value (comparable to amino acid score) and true protein digestibility.

    Differences in digestibility result from intrinsic differences in the nature of food protein and the nature of the cell wall, from the presence of other dietary factors that modify digestion (e.g., dietary fiber, polyphenols such as tannins, and enzyme inhibitors), and from chemical reactions (e.g., binding of the amino groups of lysine and cross-linkages), which may affect the release of amino acids by enzymatic processes. There are few data on the digestibility of specific amino acids in food proteins, and any differences are not captured in measurements of overall protein digestibility. Although it is known that there are differences between the pattern of amino acids in food protein, fecal matter, and portal blood, it is not now possible to provide finer adjustment than overall digestibility.

    Representative data on the digestibility of some selected proteins are shown in Table 6-6. A more comprehensive listing of protein digestibility can be found in reports by Hopkins (1981) and FAO (1970). The true digestibility of reference proteins is assigned a value of 100 for translating requirements for reference proteins to recommended levels of intake for ordinary mixtures of dietary proteins. Since the mixed protein of a typical U.S. diet is shown to be as well digested as reference proteins, no adjustment for this factor is normally required.

    Adjustment of Allowances for Dietary Quality Adjustment for exceptional dietary patterns can be made by deriving a weighted digestibility factor based on the digestibilities of the principal protein sources consumed and an amino acid score based on their contribution of essential amino acids. Such adjustment would rarely be warranted for the U.S. population. Shown in Table 6-7 is an example of calculations required to make an adjustment for an unusual diet—one in which the usual consumption pattern is reversed, i.e., only one-third of the protein from animal sources. A comparison of the amino acid pattern with the requirement patterns in Table 6-5 shows that lysine is low for the preschool age group and tryptophan is borderline. The limiting amino acid is lysine, which has a score of 51/58, or 88%. The amino acid pattern meets the requirement patterns of older children and adults, i.e., the score is 100. The weighted digestibility factor is 92%. Thus, the protein allowance for a 3-year-old child is 1.1 × 100/88 × 100/92, or 1.4 g/kg. For older children and adults, an adjustment of the allowance would be made only for digestibility.

    TABLE 6-7

    Example of Calculations Needed for Adjustment of Protein Allowances for a Diet with 33% Animal- and 67% Vegetable-Source Protein.

    11.5: Overview of amino acid catabolism and several examples - Biology

    Amino acids are organic compounds that combine to form proteins. They are the building block of proteins. They are called monomers of proteins. Some characteristics of proteins are as follows

    • There is a presence of at least one acidic carboxylic group (- COOH- ) and one basic amino group ( -NH2-).
    • Colourless, crystalline solids.
    • Water soluble and insoluble in organic solvents.
    • There are 20 amino acids in nature.
    • Eg alanine, glycine, etc. The simplest one is glycine.

    Formation of Peptide Bond

    When two amino acids are joined together by the union of&alpha- carboxyl group (-COOH ) of an amino acid with the&alpha- amino group ( -NH2 ) of other amino acids, a peptide bond is formed and a molecule of water is eliminated. This process is known as peptide linkage. The polypeptide chain is formed when amino acids are joined together in a long chain. fig:formation of peptide bond

    Types of amino acids

    20 types of amino acids are divided into two categories.

    1. Essential amino acids: Essential amino acids cannot be made by the body. As a result, they must come from food. The essential amino acids are isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
    2. Non- essential amino acids: They are produced in our body even if we do not get it from the food we eat. The 12 non-essential amino acids are alanine, serine, glycine, glutamine, tyrosine, asparatic acid, cysteine, arginine, histidine, proline, glutamic acid and asparagine.


    • Acts as the building block of protein.
    • Tyrosine gives rise to thyroxine and adrenaline hormones and melanin pigments.
    • Repair body tissues.
    • Perform many other body functions.


    Proteins are polymers of amino acids covalently linked by peptide bonds into a chain. These most the most complex chemical compounds formed of C, H, O, N, S, P. Its characteristic element is nitrogen.

    Categories of proteins.

    Depending upon their chemical nature, they are divided into three categories,

      Simple proteins: Formed of peptide chains and gives amino acids on hydrolysis. Eg globulin, histones, etc.

    Glycoproteins -Protein + Glucose. Eg mucin of saliva.
    Phosphoproteins - Amino acids + Phosphate. Eg casein of milk.
    Lipoproteins - Amino acid + Lipid. Eg Proteins of brains.
    Nucleoprotein - Amino acid + Nucleic acid. Eg chromosomes of a cell.
    Chromoprotein - Amino acid + coloured pigment. Eg haemoglobin and retina of the eye.

    On the basis of structure of molecules, proteins are classified as

    1. Globular protein consists of more than one polypeptide chains of alpha helix configuration folded up some definite manner which is held together by hydrogen bonds and cohesive forces. They are water soluble, and also in a salt solution and acids or bases. Eg albumin and globulin.
    2. Fibrous proteins twisted around each other producing some fibre - like structure. These are insoluble in water or any other reagents. Eg keratin, elastin, collagen, etc.

    Structures of protein.

    Structural features of proteins are usually described at four levels of complexity.

    • Primary structure The linear arrangement of amino acids in a protein and the location of covalent linkages such as disulphide bonds between amino acids. Eg insulin.
    • Secondary structure Here polypeptide chain bends and folds due to molecular force and gives special shapes to the protein. Eg include alpha helices and pleated sheets, which are stabilised by hydrogen bonding.
    • Tertiary structure Here, long peptide chain is coiled and variously folded by itself forming the tertiary structure having four kinds of bonds.
      Hydrogen bonds
      Ionic bonds
      Hydrophobic bond
      Disulphide bond.
    • Quaternary structure Non - covalent interactions that bind multiple polypeptides into a single, larger protein. Formed due to polymerisation of several tertiary proteins. Eg: phosphorylase.
    • fig:primary structure of protein
    • fig:Secondary structure of protein
    • fig:Tertiary structure of protein


    1. It is also known as building blocks as it plays the vital role in the maintenance of body tissue, including development and repair.
    2. Protein provides energy fuel. The caloric value of 1 gm of protein is 5.65 kcal while the physiological fuel value of 1 gm of proteins is 4.0 kcal.
    3. Proteins act as enzymes or biocatalyst which regulate life processes.
    4. Protein is involved in the creation of some hormones like insulin.
    5. Proteins are antibodies or immune- globins. They neutralise the foreign bodies and develop immunity.

    Lipids or Fats fig:Fats

    Lipids are a broad group of naturally-occurring molecules which includes fats and fat-like substances. It is the second group of organic compounds that serve as food for the body. Its characteristics are,

    • Water soluble.
    • Soluble innon- polar organic solvents like ether, acetone, etc.
    • Contains C, H, O, sometimes N or K.
    • It yields fatty acids on hydrolysis.
    • Combines with fatty acids to form esters.

    Fatty acids

    Fatty acids are straight chain organic acid. Usually, contains the even number of carbon atoms. They can be saturated ( one bond ) or unsaturated ( one or more double bond )
    General Formula = R - COOH, where
    R= CH3, CH2

    There are two types of fatty acids

    • Unsaturated fatty acids:They have one or more double bonds between the carbon atoms. They have a very low melting point. Eg oleic acid, linoleic acid, etc.
    • Saturated fatty acidsThey have no any double bond between the atoms. They have high melting point. Eg palmitic acid, stearic acid.

    Classification of Lipids

    Lipids are classified into three categories,

    1. Simple lipids.
      They are esters of fatty acids. They are divided into three types.
      • Neutral lipids:They are esters of fatty acids and glycerols hence called as glycerides. Depending upon the number of fatty acids attached to glycerol they are mono, di, or triglycerides. fig:A triglyceride fat
      • OilsThey are rich in unsaturated fatty acids. They are liquid in state.
      • WaxesThere are esters of long chain fatty acids and alcohol. They are chemically inert without double bond. They are protective in function. The important types of waxes are plant waxes, bee's wax, lanolin ( wool fat ).


    Do not fatty acids, they are nonsaponifiable, and are not hydrolysed on heating. Eg, cholesterol, diosgenin.

    • Cholesterol is a precursor molecule of many sex hormones.
    • Cholesterol on irradiation by UV rays forms vitamin D.
    • Diosgenin is used in the manufacture of anti- fertility pills.
    • Lipids provide energy fuel. The caloric value of 1 gm of fats is 9.45 kcal while the physical fuel of 1 gm of fats is 9.0 kcal.
    • Lipid acts as a heat insulator.
    • Lipids act as a solvent for fat- soluble vitamins like A, D, E, and K.
    • Absorb mechanical impact around organs like the eyeball.
    • Phospholipids form a constituent of a membrane of various organs.

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    Things to remember
    • Amino acids are building blocks of proteins.
    • 20 amino acids are found in nature.
    • Examples of amino acids are alanine, glycine, etc.
    • Amino acids are linked together in proteins by special kind of bonds called peptide bonds.
    • Proteins are the polymers made up of chains of amino acids.
    • Three categories of proteins are simple proteins, conjugated proteins, and derived proteins.
    • Protein acts as a building block, energy, enzymes, and hormones.
    • Lipids are the group of fats and fat-like substances.
    • True lipids are esters of fatty acids and alcohol.
    • Lipids are esters of fatty acids and certain alcohol.
    • Examples of fats are vanaspati ghee, Margarine and oils are mustard oil, sunflower oil, etc.
    • Cholesterol is a steroid liquid.
    • Examples of steroids area Cholesterol and Diosgenin.
    • It includes every relationship which established among the people.
    • There can be more than one community in a society. Community smaller than society.
    • It is a network of social relationships which cannot see or touched.
    • common interests and common objectives are not necessary for society.

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