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Ketone bodies are water-soluble and should pose no problem to the kidneys because of solubility. If the kidneys are able to utilize ketone bodies for energy, then they must express the enzyme 3-ketoacyl-CoA transferase, correct?
Do the kidneys express the enzyme 3-ketoacyl-CoA transferase?
Can kidneys use ketone bodies as fuel?
The primary catabolic pathway in the body is the citric acid cycle because it is here that oxidation to carbon dioxide occurs for breakdown products of the cell&rsquos major building blocks - sugars, fatty acids, and amino acids. The pathway is cyclic (Figure 6.63) and thus, doesn&rsquot really have a starting or ending point. All of the reactions occur in mitochondria, though one enzyme is embedded in the organelle&rsquos inner membrane. As needs change, cells may use a subset of the reactions of the cycle to produce a desired molecule rather than to run the entire cycle (see HERE).
Figure 6.63 - Amino acid metabolism and the citric acid cycle. Amino acids boxed in yellow are made from the indicated intermediate. Amino acids in blue are made into the intermediate in catabolism. Image by Aleia Kim
Ketone Bodies: Formation and Utilisation | Living Organisms | Biology
In this article we will discuss about:- 1. Formation of Ketone Bodies 2. Conditions Leading to Ketosis 3. Source 4. Utilisation 5. Interrelation with Carbohydrate Metabolism 6. Ratio 7. Relation of Ketosis with Blood and Urine Reaction 8. Role of Endocrine.
Formation of Ketone Bodies (Ketogenesis):
It has been observed that acetyl CoA produced during fatty acid oxidation condense with oxalo-acetic acid for oxidation in the TCA cycle. The oxalo-acetic acid formation is depressed when glucose supply is restricted so that in this condition acetyl CoA cannot be properly metabolized through citric acid cycle.
Thus acetyl CoA condenses to form aceto-acetyl CoA which in the liver produces aceto-acetic acid. The aceto-acetic acid is reduced to form β-hydroxybutyric acid which after decarboxylation forms acetones. Acetoacetic acid, acetone and β-hydroxybutyric acid are called ketone bodies.
The process of formation of ketone bodies is called ketogenesis. Normally the ketone bodies are utilized without being accumulated in the body, but they may be abnormally accumulated in body fluids known as ketosis and excreted through the urine called ketonuria (or acetonuria). Its accumulation in the blood is called ketonemia.
Site of Formation of Ketone Bodies:
Liver is perhaps the only site where ketone bodies are normally formed since concentration of ketone bodies have been found to be higher in the hepatic vein than in other veins.
These are substances which prevent the formation of ketone bodies.
They include the following:
(2) 60% of proteins (antiketogenic amino acids) from which sugar may be formed and
(3) 10% of fats (the glycerol part)
Conditions Leading to Ketosis:
The following conditions produce ketosis:
(c) High fat or low carbohydrate diet, and
Source of Ketone Bodies (Ketogenic Substances):
The ketogenic substances arise from:
(a) All fatty acids (i.e., 90% of food fat. Glycerol part burns as carbohydrates. Hence, it is antiketogenic.)
(b) Proteins (ketogenic amino acids, 40%). These are the sources from which ketone bodies are formed.
Utilisation of Ketones (Fig. 10.24):
It has been shown that ketone bodies are utilized rapidly and independently in many tissues with the produc­tion of CO2 and H2O. A significant amount of the normal energy requirement of the body is derived from this source. It has been shown that even the tissues of the diabetic animals can oxidize the ketone bodies completely even if no sugar is burnt. Recently it has been established that human brain can utilize appreciable amount of ketone bodies during prolonged starvation.
Interrelation with Carbohydrate Metabolism in Ketone Bodies:
It has been observed above that the ketone bodies only appear when enough carbohydrate is not burnt. It has also been shown that ketones can be utilized freely, without any sugar being oxidized. The interrelation between sugar oxidation and ketone formation lies in the fact that in diabetes mellitus and starvation, the glycogen content of the liver becomes low.
Since in these two conditions the fatty acids are not esterified and ketone bodies are formed. On high carbohydrate diet free fatty acid oxidation is spared. The energy requirement of the body must therefore be supplied from the oxidation of fats. For this reason fats are mobilized from the depots in large quantities and brought to the liver. Liver (whose glycogen content is already low) becomes loaded with fats.
Consequently, fat oxidation takes place at a heightened rate and more ketones are formed. They come out of the cell and enter the blood stream and finally eliminated through urine. [It is due to such leakage that normal urine shows traces of ketones.] Obviously ketones are formed at a faster rate than can be utilised. Hence ketosis may not be even due to non-utilisation of the ketone bodies but is due to their overproduction.
While prescribing diets the proportion of the ketogenic and antiketogenic substances should be so regulated that ketosis may be avoided. It is found that if the ratio between the molecules of the ketogenic substances and the molecules of the antiketogenic substances exceeds 2, ketone bodies appear in the urine. The clinical rule is that the total fat (F) content of the diet must not exceed the sum of twice the carbohydrate (C) and half of the protein (P), i.e., F = or < (2C + 1/2 P).
Rise of ketone bodies in blood above normal value is known as ketonemia.
When blood level of ketone bodies rises above the renal threshold, they are excreted in the urine. This is a condition known as ketonuria.
Accumulation of abnormal amount of ketone bodies in the tissue and tissue fluids is termed as ketosis where the urinary excretion of β-hydroxybutyric acid exceeds 200 mgm daily (normal, 5-10 mgm).
Relation of Ketosis with Blood and Urine Reaction:
During ketosis aceto-acetic acid, β-hydroxybutyric acid, etc., are formed. Since these are all acids, ketosis is usually associated with a condition of acidosis in the body and increased acidity of the urine. Due to this relation between acidosis and ketosis, acetone bodies are generally found in highly acid urine. But it must be remembered that acidosis is the result and not the cause of ketosis. A large part of acids in the urine exists— as anions. For the maintenance of neutrality cations like Na + are lost. As a result sodium salts are lost from plasma and other body fluids and consequently there is loss of body fluid resulting dehydration.
It is highly interesting that even in genuine cases of alkalosis (with alkaline urine) ketone bodies may be found in the urine. This can be demonstrated in subjects in which experimental alkalosis is produced by prolonged voluntary hyperpnoea. It is probable that in this condition β-hydroxybutyric acid, aceto-acetic acid, etc., (which is soluble and diffusible) migrate out of the cells to neutralize alkalis and are excreted in the urine.
In hospital cases alkaline urine containing acetone lodies is not an infrequent observation.
(a) Due to ammoniacal decomposition resulting from long standing,
(b) Due to therapeutic administration of alkalis to combat acidosis, and
(c) Due to true alkalosis as mentioned above.
Role of Endocrines on Ketosis:
The growth or somatotrophic hormone (STH) of anterior pituitary produces ketosis in diabetes mellitus and starvation due to inhibition of insulin secretion and depression of glycogenesis.
It prevents ketosis and its administration clears up the condition of ketosis in diabetes mellitus.
This effects is due to the following:
a. It increases liver glycogen, prevents mobilisation of fats from the depots and thus reduces liver fats. Consequently fat oxidation is discouraged and more carbohydrates burn. This leads to less ketone formation, so that ketosis disappears.
b. Insulin is antagonistic to the growth or somatotrophic hormone of anterior pituitary.
Glucocorticoids of adrenal glands are adipokinaetic, i.e., mobilise depot fat to the liver for oxidation.
Thyroxine increases ketosis under certain conditions. Its action is probably due to decrease in liver glycogen and its consequent loading with fat.
Why do we care?
To make this simple, several studies have argued that ketone oxidation is more efficient than carbohydrate or fatty acid oxidation. This was shown first by a couple of works done in Richard Veech’s lab (1, 2). Work by Benjamin Bikman’s lab showed that there are plenty of [beneficial] changes to skeletal muscle enzyme content and oxidative stress if the muscles are exposed to β‐hydroxybutyrate. More recently, it has been shown that certain tissues (such as the heart, kidney, and brain) prefer ketones to glucose, however, these studies only show rates of tissue uptake, not of substrate utilization. So, this paper looks at whether we see the same thing at the mitochondrial level as we do the whole body level or, more simply, whether the preferential ketone uptake is due to the mitochondria using the ketones as a primary fuel.
High-Protein Diet Effect on Kidneys
**A 2002 study published in the American Journal of Kidney Diseases found that a high-protein, low-carbohydrate diet raised the acidity of the blood over a six-week period, a condition known to contribute to kidney stones — specifically, uric acid stones 2. The study found up to a 90-percent increase in acid levels in the bloodstream.
In addition to the higher acid levels, the concentration of urinary citrate, a compound that inhibits the growth of kidney stones, was 25 percent lower. People consuming a diet high in protein may also become dehydrated, which concentrates the urine and may contribute to kidney stone development.
Individuals who are on a normal diet and develop kidney stones are frequently advised to reduce their intake of meat, poultry and fish protein in an attempt to prevent future kidney stones.
GNG During Fasting and Ketosis
Typically, most individuals maintain their blood glucose needs by consuming dietary carbohydrates.
However, if you’re consuming a low-carb or ketogenic diet or participating in regular intermittent fasting / time restricted eating, gluconeogenesis is likely happening at the cellular level, producing glucose to “compensate” for what you’re not eating. Let’s take a look at how GNG operates under certain dietary conditions.
Intermittent and Prolonged Fasting
There are several biological, physiological, and cellular benefits to intermittent fasting, many of which occur due to the fact that during fasting, we burn our own body fat for fuel. This occurs because after a prolonged period without eating, blood glucose (and insulin) levels begin to decline. However, blood glucose never drops to zero, and remember—we always need some glucose. Enter, gluconeogenesis.
Nearly all glucose after an overnight fast will come from our body’s own production—whether breaking down stored glycogen or creating glucose through GNG.
At this point, each metabolic pathway will contribute about half—50% for GNG and the other 50% from glycogenolysis. Nuttall2008 With continued fasting, liver and muscle glycogen stores will progressively become depleted, and gluconeogenesis will become primarily responsible for glucose production. For instance, after 40 - 72 hours without food, nearly all of the glucose produced by the body comes from gluconeogenesis. Chandramouli1997,Tayek1997,Hellerstein1997
How much glucose is provided by GNG vs. glycolysis will also depend on your pre-fast glycogen stores and the amount of physical activity or exercise you’re engaging in during the fast, among other factors. You can deplete glycogen stores quicker through exercise, and GNG will “kick in” sooner during a fast. In the same way, if you exercise before a fast or start with already low muscle and liver glycogen stores, it’ll take a lot less time to run low. Fat burning and GNG will start sooner.
Eating a ketogenic diet by definition means your body is producing ketone bodies, which then can be used by various body tissues as a source of energy.
Ketosis greatly diminishes the reliance on carbohydrates, and certain tissues will begin to require less glucose to function—preferring ketones instead. However, this doesn’t mean that the keto diet removes the glucose requirement of some other tissues gluconeogenesis still occurs to some degree even if you’re the most well-oiled fat-burning machine. For instance, red blood cells lack mitochondria, and therefore can’t use ketone bodies as an energy substrate.
The metabolic processes of ketogenesis and gluconeogenesis are compatible, both running simultaneously.
The only difference is that on a keto diet, ketones are “promoted” as the preferred fuel source, saving the small amount of glucose for where it’s needed.
Certain body tissues can run on the “credit” of ketones, while saving the glucose “cash” for those that can’t use ketone bodies.
In the initial stages of a low-carb or ketogenic diet (the fat-adaptation period), internal glucose from GNG and glycolysis will provide a good portion of glucose as an energy substrate. At this point, your ability to produce and utilize ketones isn’t quite optimized. However, after a few weeks, ketogenesis hits full force, and your body becomes a ketone-burning (and producing) machine.
It might seem paradoxical, but rates of GNG might actually increase on a ketogenic or low-carb diet, despite blood glucose levels dropping. Why does this happen? Essentially, all of the glucose you’re producing is being used for a purpose—whether it be maintaining an adequate blood glucose, providing energy for glucose-reliant tissues, or replenishing muscle glycogen.
A ketogenic diet prevents the need for excess gluconeogenesis, since this would require a lot of extra energy. Remember, producing a single glucose molecule from pyruvate requires six ATP molecules. In addition, ketones generate more energy (ATP) per gram than glucose. While 100g of glucose provides about 8.7kg of ATP, the same amount of BHB (the ketone body, beta-hydroxybutyrate) can yield 10.5kg, and acetoacetate (another ketone body) about 9.4kg. Manninen2004
This is why some body tissues (or the body as a whole) might prefer ketogenesis vs. other energy-producing metabolic pathways.
Mark Evans and Karl Cogan are graduate students at the Institute for Sport and Health, University College Dublin, Ireland. Mark received his MSc in Sport Nutrition from Liverpool John Moores University in 2015. Karl received his MSc in Biotechnology from University College Dublin in 2013. Their research explores optimising nutrition strategies for performance and recovery in athletes with specific interest in ketone bodies and protein hydrolysates, respectively.
Brendan Egan PhD is Senior Lecturer in Sport and Exercise Physiology at Dublin City University's School of Health and Human Performance, and Visiting Associate Professor at University College Dublin. His research group investigates the molecular regulation of skeletal muscle function, adaptation and performance across the life course with special interest in the synergy between nutrition and exercise interventions ranging from athletes to older adults. All three authors are accomplished sportsmen in their own right, and currently involved in the provision of sports science support to team sport athletes.
The term ‘ketone bodies’ refers to three molecules, acetoacetate (AcAc), 3-β-hydroxybutyrate (3HB) and acetone (Figure 1). AcAc accumulates during fatty acid metabolism under low carbohydrate conditions. 3HB is formed from the reduction of AcAc in the mitochondria. These two predominant ketone bodies are energy-rich compounds that transport energy from the liver to other tissues. Acetone is generated by spontaneous decarboxylation of AcAc 1 , 2 and is responsible for the sweet odor on the breath of individuals with ketoacidosis. During periods of glucose deficiency, ketone bodies play a key role in sparing glucose utilization 3 , 4 and reducing proteolysis 5 , 6 . Unlike most other tissues, the brain cannot utilize fatty acids for energy when blood glucose levels become compromised. In this case, ketone bodies provide the brain with an alternative source of energy, amounting to nearly 2/3 of the brain's energy needs during periods of prolonged fasting and starvation. Ketone bodies stimulate insulin release in vitro 7-9 , generate oxygen radicals and cause lipid peroxidation 10-13 . Lipid peroxidation and the generation of oxygen radicals may play a role in vascular disease in diabetes 10 .
Structures of major ketone bodies
Ketone bodies are present in small amounts in the blood of healthy individuals during fasting or prolonged exercise. Abnormally large quantities of ketone bodies are found in the blood of individuals who are experiencing diabetic ketoacidosis, alcoholic ketoacidosis, salicylate poisoning, and other rare conditions. Ketone bodies have been used as markers of hepatic energy metabolism following liver transplantation 14-19 . In these instances, measures of serum or urinary ketones can be useful to assess the severity of the underlying disease and to monitor treatment.
EFFECT OF KETO ON KIDNEYS
The kidneys are a pair of bean-shaped organs lying on the posterior abdominal wall on each side of the vertebral column.
Removing waste from the blood and separating the blood is the essential capacity of the kidney, consistently kidney filters out around 2 quartz of waste item and additional water.
The kidneys evacuate various waste items and dispose of them in the urine.
The second function of the kidney is the regulation of water balance.
The kidney likewise regulates the electrolyte balance in the body.
Regulation of PH level-ordinary scope of pH level is somewhere in the range of 7.38 and 7.42. Beneath this limit, the body enters a condition of acidemia, or more it, alkalemia.
Kidney also functions to maintain the acid-base balance in the body
EFFECTS OF KETO ON RENAL FUNCTION
In today’s fast life, people are more into keto diet as it has many health benefits , be it in a weight loss or in any other disease, and one of the problems is about the health benefits of kidney function in a keto diet.
Also, there are many people who are not aware about the benefits of keto diet in conditions like a renal disease. There are a great myth about kidney health and the keto diet that it influences our kidney wellbeing and is unsafe for us. The fact of the matter is keto may really improve kidney health.
Following a ketogenic diet can essentially help with weight reduction, glucose control and improve kidney work — which can help prevent kidney damage ketosis is a typical metabolic state where there is a raised degree of ketone bodies in our blood and urine.
Most individuals were not all that aware of how low carb diet can help us in kidney wellbeing and utilization of carb intake was significantly more than today in older times . So the primary source of energy was glucose that originates from carbohydrates
Since we have developed to utilize ketones for energy, keto won’t harm your kidneys health
Likewise in the present time ketones are the most used energy source over glucose as it has numerous medical advantages.
The heart and brain both run 25% all the more active when your body is utilizing ketones for energy rather than carbs and you will likewise feel energetic and lighter as the fat% additionally decreases in keto.
The Ketogenic Diet Can also Improve Kidney Function In Diabetics
Regardless of whether you have diabetes — which can put you in danger of renal disorder – , the keto diet is useful. Truth be told, a low carb, the high-fat eating routine can really improve constant renal illness, particularly in individuals with diabetes.
The Ketogenic Diet Can also Help Prevent Cardiovascular Disease in People with Chronic Kidney Disease
Saturated Fat Is Beneficial, Not Harmful, in light of the fact that natural meat doesn’t expand the danger of cardiovascular infection, the harm happens when an individual is having just processed meat and is harmful for us as well.
In keto diet we do not prescribe to have In unprocessed meats and unhealthy fats which leads to increases in the risk of heart disease by 70%
As long as we are having unprocessed meat, healthy fats, fresh vegetables, and all the other nutrients which are required In keto diet our heart and health will be solid.
As per our knowledge By having low carb, high protein diet can decrease the risk of chronic kidney disease by decreasing LDL [bad cholesterol ] and insulin level.
As long as you maintain healthy insulin levels and eat a ketogenic diet with the right macronutrient ratios, you will get into ketosis and experience the many benefits of ketones without any side effects.
If you need a quick ketone boost, try supplementing with MCT oil. This saturated fat will make it easier for your body to make ketones and adapt to the ketogenic diet.
However, don’t forget about gluconeogenesis. Without the right protein, your body will continue to use gluconeogenesis for fuel instead of shifting into ketosis.