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 >>
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 >>
Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.
Abstract Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies. Continue reading >>
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 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 >>
What Are Ketone Bodies And Why Are They In The Body?
If you eat a calorie-restricted diet for several days, you will increase the breakdown of your fat stores. However, many of your tissues cannot convert these fatty acid products directly into ATP, or cellular energy. In addition, glucose is in limited supply and must be reserved for red blood cells -- which can only use glucose for energy -- and brain tissues, which prefer to use glucose. Therefore, your liver converts many of these fatty acids into ketone bodies, which circulate in the blood and provide a fuel source for your muscles, kidneys and brain. Video of the Day Low fuel levels in your body, such as during an overnight fast or while you are dieting, cause hormones to increase the breakdown of fatty acids from your stored fat tissue. These fatty acids travel to the liver, where enzymes break the fatty acids into ketone bodies. The ketone bodies are released into the bloodstream, where they travel to tissues that have the enzymes to metabolize ketone bodies, such as your muscle, brain, kidney and intestinal cells. The breakdown product of ketone bodies goes through a series of steps to form ATP. Conditions of Ketone Body Utilization Your liver will synthesize more ketone bodies for fuel whenever your blood fatty acid levels are elevated. This will happen in response to situations that promote low blood glucose, such as an overnight fast, prolonged calorie deficit, a high-fat and low-carbohydrate diet, or during prolonged low-intensity exercise. If you eat regular meals and do not typically engage in extremely long exercise sessions, the level of ketone bodies in your blood will be highest after an overnight fast. This level will drop when you eat breakfast and will remain low as long as you eat regular meals with moderate to high carbohydrate content. Ketone Bodi Continue reading >>
Ketone Bodies
The term “ketone bodies” refers primarily to two compounds: acetoacetate and β‐hydroxy‐butyrate, which are formed from acetyl‐CoA when the supply of TCA‐cycle intermediates is low, such as in periods of prolonged fasting. They can substitute for glucose in skeletal muscle, and, to some extent, in the brain. The first step in ketone body formation is the condensation of two molecules of acetyl‐CoA in a reverse of the thiolase reaction. The product, acetoacetyl‐CoA, accepts another acetyl group from acetyl‐CoA to form β‐hydroxy‐β‐hydroxymethylglutaryl‐CoA (HMG‐CoA). HMG‐CoA has several purposes: It serves as the initial compound for cholesterol synthesis or it can be cleaved to acetoacetate and acetyl‐CoA. Acetoacetate can be reduced to β‐hydroxybutyrate or can be exported directly to the bloodstream. Acetoacetate and β‐hydroxybutyrate circulate in the blood to provide energy to the tissues. Acetoacetate can also spontaneously decarboxylate to form acetone: Although acetone is a very minor product of normal metabolism, diabetics whose disease is not well‐managed often have high levels of ketone bodies in their circulation. The acetone that is formed from decarboxylation of acetoacetate is excreted through the lungs, causing characteristic “acetone breath.” Continue reading >>
Ketone Body Formation
Ketone body formation occurs as an alternative energy source during times of prolonged stress e.g. starvation. It occurs in the liver from an initial substrate of: long chain fatty acids; the fatty acids undergo beta-oxidation by their normal pathway within mitochondria until acetyl-CoA is produced, or ketogenic amino acids; amino acids such as leucine and lysine, released at times of energy depletion, are interconverted only to acetyl-CoA Then, three molecules of acetyl-CoA are effectively joined together in three enzyme steps sequentially catalyzed by: acetyl CoA acetyltransferase HMG-CoA transferase HMG-CoA lyase Coenzyme A is regenerated and the ketone body acetoacetate is formed. Finally, acetoacetate is reduced to another ketone body, D-3-hydroxybutyrate, in a reaction catalyzed by 3-hydroxybutyrate dehydrogenase. This requires NADH. The oxidate state of the liver is such that the forward reaction is generally favoured; this results in more hydroxybutyrate being formed than acetoacetate. Continue reading >>
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 >>
What Are Ketones?
With the gradual resurgence of low-carb diets in recent years, the word “ketones” is thrown around a lot. But many people aren’t really aware of the details. What are ketones, really? And what do they do in the body? There can be a lot of misinformation regarding the answers to these questions, so read on for a full overview of ketones and their role in a ketogenic diet. Ketones, also known as “ketone bodies,” are byproducts of the body breaking down fat for energy that occurs when carbohydrate intake is low. Here’s how it works: When there isn’t a sufficient level of available glucose — which is what the body uses for its main source of fuel — and glycogen levels are depleted, blood sugar and insulin are lowered and the body looks for an alternative source of fuel: in this case, fat. This process can happen when a person fasting, after prolonged exercise, during starvation, or when eating a low-carb, ketogenic diet. And when the body begins breaking down fats for energy like this, a process known as beta-oxidation, ketones are formed for use as fuel for the body and brain. This is known as ketosis. People following a ketogenic diet specifically reduce their carbohydrate intake for this reason: to create ketones for energy. Many people use the benefits of ketosis — less reliance on carbs and more burning of fat — to possibly help lower blood pressure, reduce cravings, improve cholesterol, increase weight loss, improve energy, and more. TYPES OF KETONE BODIES So, what else about ketones do we need to know? To start, there are technically three types of ketone bodies: Acetoacetate (AcAc) Beta-hydroxybutyric acid (BHB) Acetone Both acetoacetate and beta-hydroxybutyrate are responsible for transporting energy from the liver to other tissues in the body Continue reading >>
Ketone Bodies Mimic The Life Span Extending Properties Of Caloric Restriction
The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin-like growth factor receptor signaling (IIS) pathway. Decreased IIS diminishes phosphatidylinositol (3,4,5) triphosphate (PIP3) production, leading to reduced PI3K and AKT kinase activity and decreased forkhead box O transcription factor (FOXO) phosphorylation, allowing FOXO proteins to remain in the nucleus. In the nucleus, FOXO proteins increase the transcription of genes encoding antioxidant enzymes, including superoxide dismutase 2, catalase, glutathione peroxidase, and hundreds of other genes. An effective method for combating free radical damage occurs through the metabolism of ketone bodies, ketosis being the characteristic physiological change brought about by caloric restriction from fruit flies to primates. A dietary ketone ester also decreases circulating glucose and insulin leading to decreased IIS. The ketone body, d-β-hydroxybutyrate (d-βHB), is a natural inhibitor of class I and IIa histone deacetylases that repress transcription of the FOXO3a gene. Therefore, ketosis results in transcription of the enzymes of the antioxidant pathways. In addition, the metabolism of ketone bodies results in a more negative redox potential of the NADP antioxidant system, which is a terminal destructor of oxygen free radicals. Addition of d-βHB to cultures of C. elegans extends life span. We hypothesize that increasing t Continue reading >>
Ketones
Ketones are a beneficial product of fat metabolism in the body. When carbohydrate intake is restricted, it lowers blood sugar and insulin levels. As insulin levels fall and energy is needed, fatty acids flow from the fat cells into the bloodstream and are taken up by various cells and metabolized in a process called beta-oxidation. The end result of beta-oxidation is a molecule called acetyl-coA, and as more fatty acids are released and metabolized, acetyl-coA levels in the cells rise. This causes a sort of metabolic “feedback loop” which triggers liver cells to shunt excess acetyl-Coa into ketogenesis, or the making of ketone bodies. Once created, the liver dumps the ketone bodies into the blood stream and they are taken up by skeletal and heart muscle cells at rates of availability. In addition, the brain begins to use ketones as an alternate fuel when blood levels are high enough to cross the blood brain barrier. Testing Laboratory Microbiology - Air Quality - Mold Asbestos - Environmental - Lead emsl.com There are three major types of ketone bodies present in the human blood stream when the metabolic process of ketosis is dominant: Acetoacetate (AcAc) is created first β-hydroxybutyrate (BHB) is created from acetoacetate Acetone is a spontaneously created side product of acetoacetate In times of starvation, or a low carbohydrate intake resulting in low insulin levels, ketone bodies supply up to 50% of the energy requirements for most body tissues, and up to 70% of the energy required by the brain. Glucose is the main source of fuel for neurons when the diet is high in carbohydrates. But when carbs are restricted, ketogenesis becomes the primary fuel process for most cells. During fasting or low carbohydrate intake, levels of ketone bodies in the blood stream can Continue reading >>
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 Body Formation
Sort Acetyl-CoA carboxylase in animals is regulated by A) Phosphorylation triggered by glucagon B) citrate C) palmitoyl-CoA D) All of the above D The major role of hormone-sensitive triacylglycerol lipase is to: A) hydrolyze lipids stored in the liver. B) hydrolyze triacylglycerols stored in adipose tissue. C) synthesize lipids in adipose tissue. D) synthesize triacylglycerols in the liver. b The major site of formation of acetoacetate from fatty acids is the: A) adipose tissue. B) intestinal mucosa. C) kidney. D) liver. E) muscle. d Continue reading >>
Utilization Of Ketone Bodies, Regulation And Clinical Significance Of Ketogenesis
Ketone bodies are utilized by extra hepatic tissues via a series of cytosolic reactions that are essentially a reversal of ketone body synthesis; the ketones must be reconverted to acetyl Co A in the mitochondria (figure-1) Steps 1) Utilization of β-Hydroxy Butyrate Beta-hydroxybutyrate is first oxidized to acetoacetate with the production of one NADH (Figure-1, step-1). In tissues actively utilizing ketones for energy production, NAD+/NADH ratio is always higher so as to drive the β-hydroxybutyrate dehydrogenase catalyzed reaction in the direction of acetoacetate synthesis. Biological significance D (-)-3-Hydroxybutyrate is oxidized to produce acetoacetate as well as NADH for use in oxidative phosphorylation. D (-)-3-Hydroxybutyrate is the main ketone body excreted in urine. 2) Utilization of Acetoacetate a) Coenzyme A must be added to the acetoacetate. The thioester bond is a high energy bond, so ATP equivalents must be used. In this case the energy comes from a trans esterification of the CoASH from succinyl CoA to acetoacetate by Coenzyme A transferase (Figure-1, step-2), also called Succinyl co A: Acetoacetate co A transferase, also known as Thiophorase. The Succinyl CoA comes from the TCA cycle. This reaction bypasses the Succinyl-CoA synthetase step of the TCA cycle; hence there is no GTP formation at this step although it does not alter the amount of carbon in the cycle. Biological significance The liver has acetoacetate available to supply to other organs because it lacks this particular CoA transferase and that is the reason “Ketone bodies are synthesized in the liver but utilized in the peripheral tissues”. The latter enzyme is present at high levels in most tissues except the liver. Importantly, very low-level of enzyme expression in the liver allows t Continue reading >>
