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Why Ketone Bodies Are Produced In The Body?

6 Health Benefits Of Ketogenesis And Ketone Bodies

6 Health Benefits Of Ketogenesis And Ketone Bodies

With heavy coverage in the media, ketogenic diets are all the rage right now. And for a good reason; for some people, they truly work. But what do all these different terms like ketogenesis and ketone bodies actually mean? Firstly, this article takes a look at what the ketogenesis pathway is and what ketone bodies do. Following this, it will examine six potential health benefits of ketones and nutritional ketosis. What is Ketogenesis? Ketogenesis is a biochemical process through which the body breaks down fatty acids into ketone bodies (we’ll come to those in a minute). Synthesis of ketone bodies through ketogenesis kicks in during times of carbohydrate restriction or periods of fasting. When carbohydrate is in short supply, ketones become the default energy source for our body. As a result, a diet to induce ketogenesis should ideally restrict carb intake to a maximum of around 50 grams per day (1, 2). Ketogenesis may also occur at slightly higher levels of carbohydrate intake, but for the full benefits, it is better to aim lower. When ketogenesis takes place, the body produces ketone bodies as an alternative fuel to glucose. This physiological state is known as ‘nutritional ketosis’ – the primary objective of ketogenic diets. There are various methods you can use to test if you are “in ketosis”. Key Point: Ketogenesis is a biological pathway that breaks fats down into a form of energy called ketone bodies. What Are Ketone Bodies? Ketone bodies are water-soluble compounds that act as a form of energy in the body. There are three major types of ketone body; Acetoacetate Beta-hydroxybutyrate Acetone (a compound created through the breakdown of acetoacetate) The first thing to remember is that these ketones satisfy our body’s energy requirements in the same w Continue reading >>

Ketone Bodies

Ketone Bodies

Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2], alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting)[1]. When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted Continue reading >>

Ketone Bodies Metabolism

Ketone Bodies Metabolism

1. Metabolism of ketone bodies Gandham.Rajeev Email:[email protected] 2. • Carbohydrates are essential for the metabolism of fat or FAT is burned under the fire of carbohydrates. • Acetyl CoA formed from fatty acids can enter & get oxidized in TCA cycle only when carbohydrates are available. • During starvation & diabetes mellitus, acetyl CoA takes the alternate route of formation of ketone bodies. 3. • Acetone, acetoacetate & β-hydroxybutyrate (or 3-hydroxybutyrate) are known as ketone bodies • β-hydroxybutyrate does not possess a keto (C=O) group. • Acetone & acetoacetate are true ketone bodies. • Ketone bodies are water-soluble & energy yielding. • Acetone, it cannot be metabolized 4. CH3 – C – CH3 O Acetone CH3 – C – CH2 – COO- O Acetoacetate CH3 – CH – CH2 – COO- OH I β-Hydroxybutyrate 5. • Acetoacetate is the primary ketone body. • β-hydroxybutyrate & acetone are secondary ketone bodies. • Site: • Synthesized exclusively by the liver mitochondria. • The enzymes are located in mitochondrial matrix. • Precursor: • Acetyl CoA, formed by oxidation of fatty acids, pyruvate or some amino acids 6. • Ketone body biosynthesis occurs in 5 steps as follows. 1. Condensation: • Two molecules of acetyl CoA are condensed to form acetoacetyl CoA. • This reaction is catalyzed by thiolase, an enzyme involved in the final step of β- oxidation. 7. • Acetoacetate synthesis is appropriately regarded as the reversal of thiolase reaction of fatty acid oxidation. 2. Production of HMG CoA: • Acetoacetyl CoA combines with another molecule of acetyl CoA to produce β-hydroxy β-methyl glutaryl CoA (HMC CoA). • This reaction is catalyzed by the enzyme HMG CoA synthase. 8. • Mitochondrial HMG CoA is used for ketogenesis. Continue reading >>

Fatty Acid Oxidation, Ketone Body Production

Fatty Acid Oxidation, Ketone Body Production

Sort Draw a simple diagram linking glycolysis, the TCA cycle, triglyceride breakdown and triglyceride synthesis as seen in the liver. Include some of the major substrates, intermediates, and products such as glycerol, DHAP, fatty acyl CoA, malonyl CoA and acetyl CoA. (be able to do this...) Outline the 4 steps involved in the synthesis of triglycerides from glycerol-3-phosphate and activated fatty acids. 1 fatty acid, linked to Acetyl-CoA, is added to glycerol-3-phosphate via an acyltransferase enzyme. The product here is a glycerol backbone with one R group attached (lysophosphatidic acid). Another fatty acid is added to lysophophatidic acid via a different acyltransferase enzyme, creating a molecule with a glycerol backbone and two fatty acids (phosphatidic acid). The phosphate group remaining on the final carbon of the glycerol backbone is removed by a phosphatase enzyme (making diacylglycerol), in order for... The third and final fatty acid to be added by a third acyltransferase enzyme, creating the end triacylglycerol product. Describe how fatty acids are mobilized from adipose tissue. Triacylglycerols are stored in adipocytes (fat storage cells). When fatty acids are needed by the body for energy, hormones (including epinephrine) are produced and bind to their appropriate receptors. This leads to the adenylate cyclase enzyme catalyzing the production of cAMP from ATP. A cAMP-dependent protein kinase then has the effect of activating hormone-sensitive lipase via phosphorylation. Now, this lipase is able to cleave one fatty acid from the triacylglycerol. Further removal of fatty acids is able to occur through the action of diacylglycerol- and monoacylglycerol-specific enzymes. Outline the pathway for activation and transport of the fatty acids to the mitochondrion f Continue reading >>

Ketosis, Ketone Bodies, And Ketoacidosis – An Excerpt From Modern Nutritional Diseases, 2nd Edition

Ketosis, Ketone Bodies, And Ketoacidosis – An Excerpt From Modern Nutritional Diseases, 2nd Edition

The following text is excerpted from Lipids (Chapter 8) of Modern Nutritional Diseases, 2nd Edition. Ketone Bodies and Ketosis: Ketones are organic chemicals in which an interior carbon in a molecule forms a double bond with an oxygen molecule. Acetone, a familiar chemical, is the smallest ketone possible. It is composed of three carbons, with the double bond to oxygen on the middle carbon. Biological ketone bodies include acetone, larger ketones, and biochemicals that can become ketones. The most important of the ketone bodies are hydroxybutyrate and acetoacetate, both of which are formed from condensation of two acetyl CoA molecules. Acetone is formed from a nonenzymatic decarboxylation of acetoacetate. Ketone bodies are fuel molecules that can be used for energy by all organs of the body except the liver. The production of ketone bodies is a normal, natural, and important biochemical pathway in animal biochemistry (17, p. 577). Small quantities of ketone bodies are always present in the blood, with the quantity increasing as hours without food increase. During fasting or carbohydrate deprivation, larger amounts of ketone bodies are produced to provide the energy that is normally provided by glucose. Excessive levels of circulating ketone bodies can result in ketosis, a condition in which the quantity of circulating ketone bodies is greater than the quantity the organs and tissues of the body need for energy. People who go on extremely low-carbohydrate diets to lose a large excess of body fat usually go into a mild ketosis that moderates as weight is lost. There is no scientific evidence that a low-carbohydrate diet is capable of producing sufficient ketone bodies to be harmful. Excess ketone bodies are excreted by the kidneys and lungs. Exhaled acetone gives the brea Continue reading >>

Ketones

Ketones

Excess ketones are dangerous for someone with diabetes... Low insulin, combined with relatively normal glucagon and epinephrine levels, causes fat to be released from fat cells, which then turns into ketones. Excess formation of ketones is dangerous and is a medical emergency In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketones can develop. What are ketones and why do I need to know about them? Ketones and ketoacids are alternative fuels for the body that are made when glucose is in short supply. They are made in the liver from the breakdown of fats. Ketones are formed when there is not enough sugar or glucose to supply the body’s fuel needs. This occurs overnight, and during dieting or fasting. During these periods, insulin levels are low, but glucagon and epinephrine levels are relatively normal. This combination of low insulin, and relatively normal glucagon and epinephrine levels causes fat to be released from the fat cells. The fats travel through the blood circulation to reach the liver where they are processed into ketone units. The ketone units then circulate back into the blood stream and are picked up by the muscle and other tissues to fuel your body’s metabolism. In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketone Continue reading >>

Wvsom -- Biochem

Wvsom -- Biochem

Ketone Bodies are produced in the ________ Flashcards Matching Hangman Crossword Type In Quiz Test StudyStack Study Table Bug Match Hungry Bug Unscramble Chopped Targets Oxidation of Ketone Bodies Question Answer Ketone Bodies are produced in the ________ Liver Is ketone body production a fed state or a fasted state event? Fasted State Are ketones toxic? Not as long as they can be used. Why is ketone body production and use in a fasted state? Liver Beta oxidizes esxcess fatty acids mobilized from adipocytes in teh fasted state. Acetyl-CoA produced by B oxidation is the "excess" carbon for hepatic ketone body synthesis What produces Acetyl CoA for ketone production? B-Oxidation and ketogenic amino acid catabolism Why can't the liver use all the acetyl CoA it produces in the fasted state? B-oxidation produces more Aceytl CoA than can be used Why can't the liver use all of the acetyl CoA it produces in the Fasted Stated The liver must devote significant oxaloacetate to gluconeogenesis so this limites the TCA cycle activity. What does teh liver obtain from its B-oxidation of excess fatty acids? FADH2 AND NADH are used by the liver without involvement of teh TCA cycle. Can go straight to oxidative phosphorylation NADH may provide "___________" for mitochondrial malate dehydrogenase’s production of malate from oxaloacetate. reducing power What does the body do with excess acetyl CoA carbons the liver cannot catabolize? The liver converts it to ketone bodies. What organs import ketone bodies? heart, kidney and skeletal muscle Why can high energy demand organs catabolize ketone bodies? they do not have the limit on their TCA cycle activity that hepatocytes do Can the liver use ketone bodies? no Can acetoacetyl CoA cross the plasma membrane? No What CoA is at a branch point of Continue reading >>

Ketone Bodies As Signaling Metabolites

Ketone Bodies As Signaling Metabolites

Outline of ketone body metabolism and regulation. The key irreversible step in ketogenesis is synthesis of 3-hydroxy-3-methylglutaryl-CoA by HMGCS2. Conversely, the rate limiting step in ketolysis is conversion of acetoacetate to acetoacetyl-CoA by OXCT1. HMGCS2 transcription is heavily regulated by FOXA2, mTOR, PPARα, and FGF21. HMGCS2 activity is post-translationally regulated by succinylation and acetylation/SIRT3 deacetylation. Other enzymes are regulated by cofactor availability (e.g., NAD/NADH2 ratio for BDH1). All enzymes involved in ketogenesis are acetylated and contain SIRT3 deacetylation targets, but the functional significance of this is unclear other than for HMGCS2. Although ketone bodies are thought to diffuse across most plasma membranes, the transporter SLC16A6 may be required for liver export, whereas several monocarboxylic acid transporters assist with transport across the blood–brain barrier. Abbreviations: BDH1, β-hydroxybutyrate dehydrogenase; FGF21, fibroblast growth factor 21; FOXA2, forkhead box A2; HMGCS2, 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase 2; HMGCL, HMG-CoA lyase; MCT1/2, monocarboxylic acid transporters 1/2; mTOR, mechanistic target of rapamycin; OXCT1, succinyl-CoA:3-ketoacid coenzyme A transferase; PPARα, peroxisome proliferator-activated receptor α; SIRT3, sirtuin 3; SLC16A6, solute carrier family 16 (monocarboxylic acid transporter), member 6; TCA cycle, tricarboxylic acid cycle. Continue reading >>

Ketone Ester Effects On Metabolism And Transcription

Ketone Ester Effects On Metabolism And Transcription

Abstract Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value. PRODUCTION OF KETONE BODIES Ketone bodies are formed in the liver from free fatty acids released from adipose tissue. As the blood concentration of free fatty acids increases, concentration of blood ketone bodies is correspondingly increased (1, 2). Ketone bodies serve as a physiological respiratory substrate and are the physiological response to prolonged starvation in man (3, 4), where the blood level of ketones reaches 5–7 mM (5). If the release of free fatty acids from adipose tissue exceeds the capacity of tissue to metabolize them, as occurs during insulin deficiency of type I diabetes or less commonly in the insulin resistance of type II diabetes, severe and potentially fatal diabetic ketoacidosis can occur, where blood ketone body levels can reach 20 mM or higher (2) resulting in a decrease in blood bicarbonate to almost 0 mM and blood pH to 6.9. Diabetic ketoacidosis, which is a Continue reading >>

Ketosis, Ketones, And How It All Works

Ketosis, Ketones, And How It All Works

Ketosis is a process that the body does on an everyday basis, regardless of the number of carbs you eat. Your body adapts to what is put in it, processing different types of nutrients into the fuels that it needs. Proteins, fats, and carbs can all be processed for use. Eating a low carb, high fat diet just ramps up this process, which is a normal and safe chemical reaction. When you eat carbohydrate based foods or excess amounts of protein, your body will break this down into sugar – known as glucose. Why? Glucose is needed in the creation of ATP (an energy molecule), which is a fuel that is needed for the daily activities and maintenance inside our bodies. If you’ve ever used our keto calculator to determine your caloric needs, you will see that your body uses up quite a lot of calories. It’s true, our bodies use up much of the nutrients we intake just to maintain itself on a daily basis. If you eat enough food, there will likely be an excess of glucose that your body doesn’t need. There are two main things that happen to excess glucose if your body doesn’t need it: Glycogenesis. Excess glucose will be converted to glycogen and stored in your liver and muscles. Estimates show that only about half of your daily energy can be stored as glycogen. Lipogenesis. If there’s already enough glycogen in your muscles and liver, any extra glucose will be converted into fats and stored. So, what happens to you once your body has no more glucose or glycogen? Ketosis happens. When your body has no access to food, like when you are sleeping or when you are on a ketogenic diet, the body will burn fat and create molecules called ketones. We can thank our body’s ability to switch metabolic pathways for that. These ketones are created when the body breaks down fats, creating Continue reading >>

Ketone Bodies

Ketone Bodies

Also found in: Dictionary, Thesaurus, Legal, Financial, Encyclopedia, Wikipedia. Related to ketone bodies: ketosis ketone [ke´tōn] any compound containing the carbonyl group, C=O, and having hydrocarbon groups attached to the carbonyl carbon, i.e., the carbonyl group is within a chain of carbon atoms. ketone bodies the substances acetone, acetoacetic acid, and β-hydroxybutyric acid; except for acetone (which may arise spontaneously from acetoacetic acid), they are normal metabolic products of lipid and pyruvate within the liver, and are oxidized by muscles. Excessive production leads to urinary excretion of these bodies, as in diabetes mellitus; see also ketosis. Called also acetone bodies. Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved. ketone bodies two products of lipid pyruvate metabolism, beta-hydroxybutyric acid and aminoacetic acid, from which acetone may arise spontaneously. Ketone bodies are produced from acetyl-CoA in the liver and are oxidized by the muscles. Excessive production leads to their excretion in urine, as in diabetes mellitus. Also called acetone bodies. Ketones, Blood and Urine Synonym/acronym: Ketone bodies, acetoacetate, acetone. Common use To investigate diabetes as the cause of ketoacidosis and monitor therapeutic interventions. Specimen Serum (1 mL) collected from gold-, red-, or red/gray-top tube. Urine (5 mL), random or timed specimen, collected in a clean plastic collection container. Normal findings (Method: Colorimetric nitroprusside reaction) Negative. Description Ketone bodies refer to the three intermediate products of metabolism: acetone, acetoacetic acid, and β-hydroxybutyrate. Even though β-hydroxybutyrate Continue reading >>

Ketogenesis

Ketogenesis

What is Ketogenesis? Ketogenesis (1, 2) is a biochemical process that produces ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies the needed energy of certain organs, especially the brain. Not having enough ketogenesis could result to hypoglycaemia and over production of ketone bodies leading to a condition called ketoacidosis. It releases ketones when fat is broken down for energy. There are many ways to release ketones such as through urination and exhaling acetone. Ketones have sweet smell on the breath. (3) Ketogenesis and ketoacidosis are entirely different thing. Ketoacidosis is associated with diabetes and alcoholism, which could lead to even serious condition like kidney failure and even death. Picture 1 : Ketogenic pathway Photo Source : medchrome.com Image 2 : A pyramid of ketogenic diet Photo Source : www.healthline.com What are Ketone bodies? Ketone bodies are water soluble molecules produced by the liver from fatty acids during low food intake or fasting. They are also formed when the body experienced starvation, carbohydrate restrictive diet, and prolonged intense exercises. It is also possible in people with diabetes mellitus type 1. The ketone bodies are picked up by the extra hepatic tissues and will convert to acetyl-CoA. They will enter the citric acid cycle and oxidized in the mitochondria to be used as energy. Ketone bodies are needed by the brain to convert acetyl-coA into long chain fatty acids. Ketone bodies are produced in the absence of glucose. (1, 2, 3) It is easy to detect the presence of ketone bodies. Just observe the person’s breath. The smell of the breath is fruity and sometimes described as a nail polish remover-like. It depicts the presence of acetone or ethyl acetate. The ketone bodies includ Continue reading >>

Ketone Bodies

Ketone Bodies

Overview Structure two types acetoacetate β-hydroxybutyrate β-hydroxybutyrate + NAD+ → acetoacetate + NADH ↑ NADH:NAD+ ratio results in ↑ β-hydroxybutyrate:acetoacetate ratio 1 ketone body = 2 acetyl-CoA Function produced by the liver brain can use ketones if glucose supplies fall >1 week of fasting can provide energy to body in prolonged energy needs prolonged starvation glycogen and gluconeogenic substrates are exhausted can provide energy if citric acid cycle unable to function diabetic ketoacidosis cycle component (oxaloacetate) consumed for gluconeogenesis alcoholism ethanol dehydrogenase consumes NAD+ (converts to NADH) ↑ NADH:NAD+ ratio in liver favors use of oxaloacetate for ketogenesis rather than gluconeogenesis. RBCs cannot use ketones as they lack mitochondria Synthesis occurs in hepatocyte mitochondria liver cannot use ketones as energy lacks β-ketoacyl-CoA transferase (thiophorase) which converts acetoacetate to acetoacetyl under normal conditions acetoacetate = β-hydroxybutyrate HMG CoA synthase is rate limiting enzyme Clinical relevance ketoacidosis pathogenesis ↑ ketone levels caused by poorly controlled type I diabetes mellitus liver ketone production exceeds ketone consumption in periphery possible in type II diabetes mellitus but rare alcoholism chronic hypoglycemia results in ↑ ketone production presentation β-hydroxybutyrate > acetoacetate due to ↑ NADH:NAD+ ratio acetone gives breath a fruity odor polyuria ↑ thirst tests ↓ plasma HCO3 hypokalemia individuals are initially hyperkalemic (lack of insulin + acidosis) because K leaves the cells overall though the total body K is depleted replete K in these patients once the hyperkalemia begins to correct nitroprusside urine test for ketones may not be strongly + does not detect Continue reading >>

Introduction To Degradation Of Lipids And Ketone Bodies Metabolism

Introduction To Degradation Of Lipids And Ketone Bodies Metabolism

Content: 1. Introduction to degradation of lipids and ketone bodies metabolism 2. Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids 3. Synthesis and utilisation of ketone bodies _ Triacylglycerol (TAG) contain huge amounts of chemical energy. It is very profitable to store energy in TAG because 1 g of water-free TAG stores 5 times more energy than 1 g of hydrated glycogen. Complete oxidation of 1 g of TAG yields 38 kJ, 1g of saccharides or proteins only 17 kJ. Man that weighs 70 kg has 400 000 kJ in his TAG (that weight approximately 10,5 kg). This reserve of energy makes us able to survive starving in weeks. TAG accumulate predominantly in adipocyte cytoplasm. There are more types of fatty acid oxidation. Individual types can be distinguished by different Greek letters. Greek letter denote atom in the fatty acid chain where reactions take place. β-oxidation is of major importance, it is localised in mitochondrial matrix. ω- and α- oxidation are localised in endoplasmic reticulum. Animal cells cannot convert fatty acids to glucose. Gluconeogenesis requires besides other things (1) energy, (2) carbon residues. Fatty acids are rich source of energy but they are not source of carbon residues (there is however one important exception, i.e. odd-numbered fatty acids). This is because cells are not able to convert AcCoA to neither pyruvate, nor OAA. Both carbons are split away as CO2. PDH is irreversible. Plant cells are capable of conversion of AcCoA to OAA in glyoxylate cycle. _ Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids Lipids are used for energy production, this process take place in 3 phases: 1) Lipid mobilisation – hydrolysis of TAG to FA and glycerol. FA and glycerol are transported Continue reading >>

Ketone Bodies As A Fuel For The Brain During Starvation

Ketone Bodies As A Fuel For The Brain During Starvation

THE STATUS OF OUR KNOWLEDGE OF STARVATION AND BRAIN METABOLISM IN HUMANS WHEN I BEGAN MY RESEARCH This story begins in the early 1960s when the general level of knowledge about whole-body metabolism during human starvation was grossly deficient. This was partly caused by a lack of accurate and specific methods for measuring hormones and fuels in biological fluids, which became available about 1965.11 Rigidly designed protocols for studying human volunteers or obese patients, who underwent semi- or total starvation for prolonged periods of time, were not widely employed, and much of the published data regarding metabolic events during starvation were not readily accessible. To complicate matters further, a great deal of the available data was confusing because much of the supposition regarding mechanisms used by the body to survive prolonged periods of starvation was based upon information that was obtained from nonstandardized and often erroneous procedures for studying metabolism. For example, the rate of urinary nitrogen excretion during starvation was sometimes confounded by the consumption of carbohydrate during the studies. Today, students of biochemistry take for granted the fact that tissues of the human body have a hierarchy of fuel usage. They know that the brain, an organ devoted to using glucose, can switch to use ketone bodies during prolonged starvation (2–3 days), thus sparing glucose for other tissues (i.e. red blood cells must use glucose as a fuel; without mitochondria, they have no choice!). However, this fundamental insight into human metabolism was not recognized in the early 1960s, when my research in this area began. How this simple but fundamental fact that ketone bodies provide critical fuels for the brain was discovered and its implication for Continue reading >>

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