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What Is The Conversion Of Acetyl Coa Into Ketone Bodies

Ketone Body Metabolism

Ketone Body Metabolism

Ketone body metabolism includes ketone body synthesis (ketogenesis) and breakdown (ketolysis). When the body goes from the fed to the fasted state the liver switches from an organ of carbohydrate utilization and fatty acid synthesis to one of fatty acid oxidation and ketone body production. This metabolic switch is amplified in uncontrolled diabetes. In these states the fat-derived energy (ketone bodies) generated in the liver enter the blood stream and are used by other organs, such as the brain, heart, kidney cortex and skeletal muscle. Ketone bodies are particularly important for the brain which has no other substantial non-glucose-derived energy source. The two main ketone bodies are acetoacetate (AcAc) and 3-hydroxybutyrate (3HB) also referred to as β-hydroxybutyrate, with acetone the third, and least abundant. Ketone bodies are always present in the blood and their levels increase during fasting and prolonged exercise. After an over-night fast, ketone bodies supply 2–6% of the body's energy requirements, while they supply 30–40% of the energy needs after a 3-day fast. When they build up in the blood they spill over into the urine. The presence of elevated ketone bodies in the blood is termed ketosis and the presence of ketone bodies in the urine is called ketonuria. The body can also rid itself of acetone through the lungs which gives the breath a fruity odour. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones. Ketone bodies The term ‘ketone bodies’ refers to three molecules, acetoacetate (AcAc), 3-hydroxybutyrate (3HB) and acetone (Figure 1). 3HB is formed from the reduction of AcAc i Continue reading >>

Ketone Bodies Metabolic Pathway (pw:0000069)

Ketone Bodies Metabolic Pathway (pw:0000069)

Description The ketone bodies metabolic pathway is used to convert acetyl-CoA formed in the liver into "ketone bodies": acetone, and more importantly acetoacetate and 3-hydroxybutyrate, which are transported in the blood to extrahepatic tissues where they are converted to acetyl-CoA and oxidized via the citrate cycle pathway for energy. The brain, which usually uses glucose for energy, can utilize ketone bodies under starvation conditions, when glucose is not available. When acetyl-CoA is not being metaboli...(more) Description: ENCODES a protein that exhibits 3-hydroxybutyrate dehydrogenase activity (ortholog); NAD binding (ortholog); oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor (ortholog); INVOLVED IN epithelial cell differentiation (ortholog); fatty acid beta-oxidation (ortholog); heme metabolic process (ortholog); PARTICIPATES IN butanoate metabolic pathway; ketone bodies metabolic pathway; FOUND IN cytoplasm (ortholog); cytosol (ortholog); extracellular exosome (ortholog); INTERACTS WITH 2,3,7,8-tetrachlorodibenzodioxine; 2,4-dinitrotoluene; 2,6-dinitrotoluene 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 >>

Bcii: Ketone Bodies

Bcii: Ketone Bodies

Sort 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. liver. Ketone bodies are formed in the liver and transported to the extrahepatic tissues mainly as: a. acetoacetyl-CoA. b. acetone. c. beta-hydroxybutyric acid. d. beta-hydroxybutyryl-CoA. e. lactic acid. b. acetone. Continue reading >>

Lipid Metabolism

Lipid Metabolism

on on Fats (or triglycerides) within the body are ingested as food or synthesized by adipocytes or hepatocytes from carbohydrate precursors ([link]). Lipid metabolism entails the oxidation of fatty acids to either generate energy or synthesize new lipids from smaller constituent molecules. Lipid metabolism is associated with carbohydrate metabolism, as products of glucose (such as acetyl CoA) can be converted into lipids. Lipid metabolism begins in the intestine where ingested triglycerides are broken down into smaller chain fatty acids and subsequently into monoglyceride molecules (see [link]b) by pancreatic lipases, enzymes that break down fats after they are emulsified by bile salts. When food reaches the small intestine in the form of chyme, a digestive hormone called cholecystokinin (CCK) is released by intestinal cells in the intestinal mucosa. CCK stimulates the release of pancreatic lipase from the pancreas and stimulates the contraction of the gallbladder to release stored bile salts into the intestine. CCK also travels to the brain, where it can act as a hunger suppressant. Together, the pancreatic lipases and bile salts break down triglycerides into free fatty acids. These fatty acids can be transported across the intestinal membrane. However, once they cross the membrane, they are recombined to again form triglyceride molecules. Within the intestinal cells, these triglycerides are packaged along with cholesterol molecules in phospholipid vesicles called chylomicrons ([link]). The chylomicrons enable fats and cholesterol to move within the aqueous environment of your lymphatic and circulatory systems. Chylomicrons leave the enterocytes by exocytosis and enter the lymphatic system via lacteals in the villi of the intestine. From the lymphatic system, the chylo Continue reading >>

Chapter 7

Chapter 7

Metabolic pathway Catabolism Anabolism Mitochondria ATP NADH FADH GTP ADP AMP NADPH A series of chemical reactions that either break down a large compound into small pieces or synthesize bigger compounds from smaller molecules Breaking down large particles into smaller ones. Process which cells change smaller compounds into larger more complex ones. Where most of the ATP is captured when being made from CHO,PRO or FAT. Called the "power plant" of the cells. High energy molecules which is what fuels most of the cells and is used to synthesize molecules. Reduced form of NAD, acts as an electron carrier in cells and undergoes oxidation and reduction Reduced form of FAD, also acts like an electron carrier and undergoes oxidation and reduction Similar to ATP, but with 3 phosphates linked to guanosine. Compound produced upon hydrolysis of ATP and is used to synthesize ATP Product of hydrolysis from ADP and nucleic acids. Reduced form of NADP. Also acts as an electron carrier in cells and undergoes reduction and oxidation. Glycolysis Aerobic Anaerobic Pyruvate Lactate Krebs cycle Citrate Oxalate Anaerobic pathway of breaking down glucose molecules into 2 molecules of pyruvate and creates 2 molecules of ATP and NADH. Occurs in cytosol. Needs oxygen in order for metabolic pathway to happen No need of oxygen for the metabolic pathway to happen 3 carbon compound that is created from the breakdown of glucose, can also be derived from amino acids and glycerol. Ionized form of lactic acid and is produced when there is a lack of oxygen in cells to produce pyruvate Also known as citric acid cycle, takes place in mitochondria where acetyl part of acetyl CoA is oxidized to yield 2 CO2, and NADH, FADH2, and GTP. Organic acid which can be found in some leafy green veggies that binds to cal Continue reading >>

Understanding Ketosis

Understanding Ketosis

To gain a better understanding of ketosis and the ketogenic diet, it is important to take a look at the physiology behind the diet. If you recall from the article What is a Ketogenic Diet? the goal of a ketogenic diet is to induce ketosis by increasing ketone body production. A key step in understanding the diet is to learn what ketosis is, what are ketones and what do they do. “Normal” Metabolism Learning the basics of the various metabolic processes of the body will better your ability to understand ketosis. Under the normal physiological conditions that are common today, glucose is our body’s primary source of energy. Following ingestion, carbohydrates are broken down into glucose and released into the blood stream. This results in the release of insulin from the pancreas. Insulin not only inhibits fat oxidation but also acts as a key holder for cells by allowing glucose from the blood to be shuttled into cells via glucose transporters (GLUT). The amount of insulin required for this action varies between individuals depending on their insulin sensitivity. Once inside the cell, glucose undergoes glycolysis, a metabolic process that produces pyruvate and energy in the form of adenosine triphosphate (ATP). Once pyruvate is formed as an end product of glycolysis, it is shuttled into the mitochondria, where it is converted to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA then enters the TCA cycle to produce additional energy with the aid of the electron transport chain. Since glucose is so rapidly metabolized for energy production and has a limited storage capacity, other energy substrates, such as fat, get stored as triglycerides due to our body’s virtually infinite fat storage capacity. When a sufficient source of carbohydrates is not available, the body adap Continue reading >>

Multiple Choice Quiz 1

Multiple Choice Quiz 1

(See related pages) 1 Which one of the following would not be a nutrient? 2 Most vitamins, minerals, and water all have this in common: 3 When the body metabolizes nutrients for energy, fats yield about _______ times the energy as carbohydrates or proteins. 4 A calorie is the amount of energy necessary to raise the temperature of one gram of _________ one degree __________. 5 One piece of apple pie would yield about 6 The disaccharide that most people think of as table sugar is 7 When lactose is digested, it yields two monosaccharides called 8 The complex carbohydrate (polysaccharide) that is digested to the monosaccharide, glucose, and is found in vegetables, fruits, and grains and is called 9 If excess glucose is present in the body, the glucose first will be stored as __________ in muscle and the liver. 10 Triglycerides that contain one or more double covalent bonds between carbon atoms of their fatty acids are called 11 Bubbling hydrogen gas through polyunsaturated vegetable oil will cause the oil to become more 12 The lipid that is a component of the plasma membrane and can be used to form bile salts and steroid hormones is 13 The American Heart Association recommends that saturated fats should contribute no more than 10% of total fat intake. Excess fats, especially cholesterol and saturated fat, can increase the risk of 16 The daily-recommended consumption amount of protein for a healthy adult is about _____% of total kilocalorie intake per day. 20 Inorganic nutrients that are necessary for normal metabolism are called 23 When a molecule loses an electron, that molecule is said to be ___________ and often a(n) _____________ ion is lost along with the electron. 25 When a hydrogen ion and an associated electron are lost from a nutrient molecule, which of the followi Continue reading >>

Mbm 16 €“ Ketone Body Metabolism. Purpose, Connections And Control

Mbm 16 €“ Ketone Body Metabolism. Purpose, Connections And Control

MedSoc Teaching MBM Session 5 Habillan Naathan (mzyhn2) Objectives * Understand the role of ketone bodies in human metabolism. * Be able to describe the ketone bodies their metabolism. * Have an overview of the role of ketone bodies in diabetes and starvation. Ketone Bodies ï€ Starvation: ï€ blood glucose drops very low, endangering the brain ï€ Mobilisation of fatty acids from adipose tissue (glucagon high) BUT- PROBLEM! ï€ Brain cannot use ….. ï€ Liver: TCA cycle cannot utilise all the …. from β-oxidation ï‚· citrate synthase not active enough ï‚® accumulation of acetyl CoA ï€ Liver: acetylCoA diverted to ketone bodies ï€ Can be utilised by muscle, kidney and eventually the brain under starvation conditions or in diabetes ï€ When in excess, acetyl CoA produced from β-oxidation of fatty acids, is converted into …………………….. and ………………………. ï€ Together with acetone these compounds collectively termed ketone bodies ï€ Acetone formed during ketosis but cannot be utilized ï‚® excreted on breath producing typical smell of a ketotic individual (acetone not metabolized) ï€ Ketosis occurs during starvation and diabetes (when glucose utilisation is impaired) MedSoc Teaching MBM Session 5 Habillan Naathan (mzyhn2) ï€ Babies can become ketotic quickly due to small glycogen stores Ketone Body Synthesis ï€ 2 molecules acetyl CoA initially condense to form acetoacetyl CoA ï‚® reverse of thiolysis step in β-oxidation ï€ Acetoacetyl CoA reacts with another molecule of acetyl CoA to form ………………………………………. (HMG CoA) ï€ Th Continue reading >>

Ketogenesis (biosynthesis Of Ketone Bodies)

Ketogenesis (biosynthesis Of Ketone Bodies)

In humans, liver mitochondria have capacity to divert any excess acetyl-CoA formed in the liver during oxidation of fatty acids or oxidation of pyruvate that exceed capacity of citric acid cycle to undergo conversion to the ketone bodies. ketone bodies : [acetoacetate, D-β-hydroxybutyrate& acetone (non metabolizable side product)] for export to other tissues, where they can reconvert to acetyl CoA & oxidized by citric acid cycle. * Ketone bodies are important sources of energy for the peripheral tissues because: They are soluble in aqueous solution (don't need to be incorporated into lipoproteins or carried by albumin like lipid). 2. Produced in liver during periods when acetyl-CoA present exceed the oxidative capacity of the liver. How 3. They are used in proportion to their concentration in the blood by extrahepatic tissues (skeletal & cardiac muscle & renal cortex). Brain, heart & muscle can use ketone bodies to meet their energy needs if the blood levels rise sufficiently (during prolonged periods of fasting). Why ketone bodies synthesized by the liver: The production and export of ketone bodies from the liver to extrahepatic tissues allow continued oxidation of fatty acids in the liver when acetyl-CoA is not being oxidized in the citric acid cycle. * Synthesis of ketone bodies 1-Formation of acetoacetyl CoA can occur by one of 2 processes: a. Incomplete breakdown of fatty acid. b. Enzymatic condensation of two molecules of acetyl-CoA, which catalyzed by thiolase (the reversal of thiolase reaction of fatty acid oxidation). 2- The acetoacetyl-CoA, condenses with 3rd molecule of acetyl-CoA to form β -hydroxy- β -methylglutaryl-CoA (HMG-CoA) catalyzed by HMG-CoA synthase (the rate limiting step in the synthesis of ketone bodies & present in significant quantit Continue reading >>

Ketone Body Synthesis

Ketone Body Synthesis

Types of Ketone Bodies and Their Function There are three substances in our body that are considered ketone bodies: Acetoacetate is a metabolic product of the liver. It can be converted into acetone and beta-hydroxybutyrate. Acetone is a product of spontaneous decarboxylation of acetoacetate or via the action of acetoacetate decarboxylase. It is disposed of with the respiratory air or in the urine. Acetone does not have any function in our metabolism. Beta-hydroxybutyrate is not a ketone body strictly speaking. It is derived from acetoacetate via the action of D-beta hydroxy butyrate dehydrogenase. It is the most abundant ketone body. Acetoacetate and beta-hydroxybutyrate are only synthesized in the mitochondrial matrix of hepatocytes. Brain, myocardial and skeletal muscles all rely on the re-conversion of these substances in times of low glucose levelssince they can traverse membranes easily. Since the brain cannot use fatty acids for energy generation because the blood-brain barrier is not permeable to fatty acids, it is dependent on ketone bodies in periods of fasting as its sole energy resource. Using ketone bodies, the brain can reduce its glucose demand from an average of about 150g/day to about 50g/day.They are transported to the brain via monocarboxylate transporters 1 and 2. Activation of Ketone Body Synthesis From a biochemical perspective, ketone body synthesis will be reinforced whenever there is an increased presence of acetyl-CoA (the starting substance of ketone body synthesis), as is the case during longer periods of fasting or starvation. Furthermore, diabetes mellitus causes an accumulation of acetyl-CoA: the lower insulin production or higher insulin resistance leads to an increase in the degradation of fatty acids which, in turn, leads to more acetyl Continue reading >>

Ketogenesis

Ketogenesis

Ketogenesis pathway. The three ketone bodies (acetoacetate, acetone, and beta-hydroxy-butyrate) are marked within an orange box Ketogenesis is the biochemical process by which organisms produce a group of substances collectively known as ketone bodies by the breakdown of fatty acids and ketogenic amino acids.[1][2] This process supplies energy to certain organs (particularly the brain) under circumstances such as fasting, but insufficient ketogenesis can cause hypoglycemia and excessive production of ketone bodies leads to a dangerous state known as ketoacidosis.[3] Production[edit] Ketone bodies are produced mainly in the mitochondria of liver cells, and synthesis can occur in response to an unavailability of blood glucose, such as during fasting.[3] Other cells are capable of carrying out ketogenesis, but they are not as effective at doing so.[4] Ketogenesis occurs constantly in a healthy individual.[5] Ketogenesis takes place in the setting of low glucose levels in the blood, after exhaustion of other cellular carbohydrate stores, such as glycogen.[citation needed] It can also take place when there is insufficient insulin (e.g. in type 1 (but not 2) diabetes), particularly during periods of "ketogenic stress" such as intercurrent illness.[3] The production of ketone bodies is then initiated to make available energy that is stored as fatty acids. Fatty acids are enzymatically broken down in β-oxidation to form acetyl-CoA. Under normal conditions, acetyl-CoA is further oxidized by the citric acid cycle (TCA/Krebs cycle) and then by the mitochondrial electron transport chain to release energy. However, if the amounts of acetyl-CoA generated in fatty-acid β-oxidation challenge the processing capacity of the TCA cycle; i.e. if activity in TCA cycle is low due to low amo 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

Sort Ketone Bodies -->Represent 3 molecules that are formed when excess acetyl CoA cannot enter the TCA Cycle -->Represents 3 major molecules: 1)Acetoacetate 2)β-Hydroxybutyrate 3)Acetone -->Normal people produces ketones at a low rate -->Are only formed in the **LIVER**(by liver mitochondria) Reactions that lead to the formation of ketone bodies (***See pwrpt***) 1)2 Acetyl CoA molecules condense to form ***Acetoacetyl-CoA -->Is catalyzed by THIOLASE -->Represent the oppostie of thiolysis step in the oxidation of fatty acids -->Represent the parent compound of the 3 ketone bodies (2)Acetoacetyl CoA then reacts with another mol. of acetyl CoA to form **HMG-CoA* (3-hydroxy-3-methylglutaryl CoA) & *CoA** -->Reaction is catalyzed by **HMG-CoA Synthetase** -->HMG-CoA has 2 fates (can either progress to form ketone bodies OR can enter the pathway of CHOLESTEROL synthesis) -->Represent the **RATE-LIMITING STEP** in the synthesis of ketone bodies (3)HMG-CoA is cleaved to form **Acetoacetate**(First major ketone; represent ~20% of ketones) & another mol. of acetyl CoA -->Catalyzed by **HMG-CoA Lyase** (4) Acetoacetae can lead to the formation of β-hydroxybutyrate (~78% of ketone bodies) & Acetone (~2% of ketone bodies) via 2 separte reactions Interrelationships of the ketone bodies from Acetoacetate (1)Formation of β-hydroxybutyrate -->Acetoacetate will be reduced to form β-hyroxybutyrate in the mitochondrial matrix of the liver cell -->Is a REVERSIBLE RXN. -->Requires 1 mol of NADH (***Dependent on the NADH/NAD ratio inside the mitochondria) -->Catalyzed by β-hydroxybutyrate dehydrogenase (2)Formation of Acetone -->A slower, **spontaneous** decarboxylation to acetone -->In **DIABETIC KETOACIDOSIS, acetone imparts a characteristic smell to the patient's breath Features of 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 >>

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