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Ketone Bodies Synthesis

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 Formed In The Liver Are Exported To Other Organs

Ketone Bodies Formed In The Liver Are Exported To Other Organs

Ketone Bodies In human beings and most other mammals, acetyl-CoA formed in the liver during oxidation of fatty acids may enter the citric acid cycle (stage 2 of Fig. 16-7) or it may be converted to the "ketone bodies" acetoacetate, D-β-hydroxybutyrate, and acetone for export to other tissues. (The term "bodies" is a historical artifact; these compounds are soluble in blood and urine.) Acetone, produced in smaller quantities than the other ketone bodies, is exhaled. Acetoacetate and D-β-hydroxybutyrate are transported by the blood to the extrahepatic tissues, where they are oxidized via the citric acid cycle to provide much of the energy required by tissues such as skeletal and heart muscle and the renal cortex. The brain, which normally prefers glucose as a fuel, can adapt to the use of acetoacetate or D-β-hydroxybutyrate under starvation conditions, when glucose is unavailable. A major determinant of the pathway taken by acetyl-CoA in liver mitochondria is the availability of oxaloacetate to initiate entry of acetyl-CoA into the citric acid cycle. Under some circumstances (such as starvation) oxaloacetate is drawn out of the citric acid cycle for use in synthesizing glucose. When the oxaloacetate concentration is very low, little acetyl-CoA enters the cycle, and ketone body formation is favored. The production and export of ketone bodies from the liver to extrahepatic tissues allows continued oxidation of fatty acids in the liver when acetyl-CoA is not being oxidized via the citric acid cycle. Overproduction of ketone bodies can occur in conditions of severe starvation and in uncontrolled diabetes. The first step in formation of acetoacetate in the liver (Fig. 16-16) is the enzymatic condensation of two molecules of acetyl-CoA, catalyzed by thiolase; this is simply Continue reading >>

Ketone Body Synthesis In The Brain: Possible Neuroprotective Effects.

Ketone Body Synthesis In The Brain: Possible Neuroprotective Effects.

Abstract Ketone bodies make an important contribution to brain energy production and biosynthetic processes when glucose becomes scarce. Although it is generally assumed that the liver supplies the brain with ketone bodies, recent evidence shows that cultured astrocytes are also ketogenic cells. Moreover, astrocyte ketogenesis might participate in the control of the survival/death decision of neural cells in at least two manners: first, by scavenging non-esterified fatty acids the ketogenic pathway would prevent the detrimental actions of these compounds and their derivatives (e.g. ceramide) on brain structure and function. Second, ketone bodies may exert pro-survival actions per se by acting as cellular substrates, thereby preserving neuronal synaptic function and structural stability. These findings support the notion that ketone bodies produced by astrocytes may be used in situ as substrates for neuronal metabolism, and raise the possibility that astrocyte ketogenesis is a neuroprotective pathway. Continue reading >>

6.9: Ketone Body Synthesis

6.9: Ketone Body Synthesis

In ketone body synthesis, an acetyl-CoA is split off from HMG-CoA, yielding acetoacetate, a four carbon ketone body that is somewhat unstable, chemically. It will decarboxylate spontaneously to some extent to yield acetone. Ketone bodies are made when the blood levels of glucose fall very low. Ketone bodies can be converted to acetyl-CoA, which can be used for ATP synthesis via the citric acid cycle. People who are very hypoglycemic (including some diabetics) will produce ketone bodies and these are often first detected by the smell of acetone on their breath. Figure 6.9.1: Ketone Body Reactions Acetone is of virtually no use for energy production since it is not readily converted to acetyl-CoA. Consequently, cells convert acetoacetate into beta- hydroxybutyrate, which is more chemically stable. Though technically not a ketone, beta-hydroxybutyrate is frequently referred to as a ketone body. Upon arrival at a target cell, it can be oxidized back to acetoacetate with conversion to acetyl-CoA. Both acetoacetate and beta-hydroxybutyrate can cross the blood-brain barrier and provide important energy for the brain when glucose is limiting. Continue reading >>

Ketone Body Synthesis

Ketone Body Synthesis

Sort 1. Ketone body synthesis: Ketone bodies are x forms of lipid-based energy and consist mainly of x acid and its reduction product, x acid. β-hydroxybutyryl CoA and acetoacetyl CoA are x near the end of the β-oxidation scheme. x in an intermediate in the synthesis of acetoacetate from Acetyl CoA The primary site for formation of ketone bodies is x, with lesser activity in x. The entire process occurs within the x, beginning with condensation of two acetyl CoA molecules to make acetoacetyl CoA, as catalyzed by xase. Acetoacetyl CoA then condenses with another acetyl CoA to form β- hydroxymethylglutaryl coenzyme A (aka x). Cleavage of HMG CoA by HMG CoA xase yields acetoacetic acid and acetyl CoA. 1. Ketone body synthesis: Ketone bodies are water soluble forms of lipid-based energy and consist mainly of acetoacetic acid and its reduction product, β-hydroxybutyric acid. β-hydroxybutyryl CoA and acetoacetyl CoA are intermediates near the end of the β-oxidation scheme. HMG-CoA in an intermediate in the synthesis of acetoacetate from Acetyl CoA The primary site for formation of ketone bodies is liver, with lesser activity in kidney. The entire process occurs within the mitochondrial matrix, beginning with condensation of two acetyl CoA molecules to make acetoacetyl CoA, as catalyzed by β-ketothiolase. Acetoacetyl CoA then condenses with another acetyl CoA to form β- hydroxymethylglutaryl coenzyme A (aka HMG CoA). Cleavage of HMG CoA by HMG CoA Lyase yields acetoacetic acid and acetyl CoA. Acetoacetate Forms both D-β-Hydroxybutyrate and acetone In mitochondria a fraction of acetoacetate is reduced to D-β-hydroxybutyrate depending on the intramitochondrial x ratio. Some acetoacetate continually undergoes slow spontaneous nonx decarboxylation to acetone. In these pa Continue reading >>

Ketone Bodies

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

Ketone

ke·tone (kē′tōn′) n. 1. Any of a class of organic compounds, such as acetone, characterized by having a carbonyl group in which the carbon atom is bonded to two other hydrocarbon groups and having the general formula R(CO)R′, where R may be the same as R′. [German Keton, shortening and alteration of Aceton, acetone : Latin acētum, vinegar; see acetum + German -on, n. suff. (alteration of -en, from Greek -ēnē).] American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2016 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved. ketone (ˈkiːtəʊn) [C19: from German Keton, from Aketon acetone] Collins English Dictionary – Complete and Unabridged, 12th Edition 2014 © HarperCollins Publishers 1991, 1994, 1998, 2000, 2003, 2006, 2007, 2009, 2011, 2014 ke•tone (ˈki toʊn) n. any of a class of organic compounds containing a carbonyl group, CO, attached to two alkyl groups, as CH3COCH3. Random House Kernerman Webster's College Dictionary, © 2010 K Dictionaries Ltd. Copyright 2005, 1997, 1991 by Random House, Inc. All rights reserved. ke·tone (kē′tōn′) Any of a class of organic compounds, such as acetone, having a group consisting of a carbon and an oxygen atom (CO) joined on either side to a carbon atom of a hydrocarbon radical. The American Heritage® Student Science Dictionary, Second Edition. Copyright © 2014 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved. Noun 1. ketone - any of a class of organic compounds having a carbonyl group linked to a carbon atom in each of two hydrocarbon radicalsnabumetone, Relafen - a nonsteroidal anti-inflammatory drug (trade name Relafe 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 >>

Utilization Of Ketone Bodies, Regulation And Clinical Significance Of Ketogenesis

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 >>

Synthesis And Degradation Of Ketone Bodies (homo Sapiens)

Synthesis And Degradation Of Ketone Bodies (homo Sapiens)

Description Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting. Source: Wikipedia Ontology Terms Compare Revision Action Time User Comment 68921FeaturedApproved view 17:32, 8 July 2013 MaintBot Updated to 2013 gpml schema 67674 view 11:47, 26 June 2013 Ddigles Ontology Term : 'ketone bodies metabolic pathway' added ! 61697 view 23:23, 16 April 2013 MaintBot removed data source without identifer 48248 view 06:21, 17 May 2012 MaintBot Updating PubChem xrefs 48220 view 05:29, 17 May 2012 MaintBot Automatic update of PubChem xrefs 45110 view 22:36, 6 October 2011 Khanspers Ontology Term : 'ketone bodies biosynthetic pathway' added ! 45108 view 22:36, 6 October 2011 Khanspers Ontology Term : 'ketone bodies degradation pathway' added ! 43510 view 09:33, 24 June 2011 AdrienDefay add database name + database ID 41068 view 23:19, 1 March 2011 MaintBot Removed redundant pathway information and comments 38846 view 17:47, 24 September 2010 Khanspers 38738 view 21:54, 23 September 2010 Khanspers Changed interactions 38736 view 21:52, 23 September 2010 Khanspers Added pathway links, Changed lines 38735 view 21:47, 23 September 2010 Khanspers Added pathway links 35389 view 09:33, 12 February 2010 Thomas fixed connections 35359 view 09:09, 12 February 2010 Thomas fixed reference 35355 view 09:07, 12 February 2010 Thomas Modified description 35354 view 09:07, 12 February 2010 Thomas added literature 34452 view 18:23, 10 December 2009 MaintBot Automatic update of empty xrefs 21335 view 11:31, 14 November 2008 MaintBot [[Pathway:Homo sapiens:Synthesis and Degradation of Continue reading >>

Ketone

Ketone

(redirected from Synthesis and degradation of ketone bodies) Also found in: Dictionary, Thesaurus, Encyclopedia. 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. ke·tone (kē'tōn), Any organic compound in which two carbon atoms are linked by the carbon of a carbonyl group (C-O). The simplest ketone and the most important in medicine is dimethyl ketone (acetone). ketone /ke·tone/ (ke´tōn) any of a class of organic compounds containing the carbonyl group, CdbondO, whose carbon atom is joined to two other carbon atoms, i.e., with the carbonyl group occurring within the carbon chain. ketone (kē′tōn′) n. 1. Any of a class of organic compounds, such as acetone, characterized by having a carbonyl group in which the carbon atom is bonded to two other hydrocarbon groups and having the general formula R(CO)R′, where R may be the same as R′. ketone an organic chemical compound characterized by having in its structure a carbonyl, or keto, group, ═CO, attached to two alkyl groups. It is produced by oxidation of secondary alcohols. ke·tone (kē'tōn) A substance with the 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 >>

Ketone Bodies

Ketone Bodies

The use of ketone bodies as fuel by most tissues during a fast reduces the need for gluconeogenesis from amino acid carbon skeletons, slowing the loss of essential protein. During a fast, the liver is flooded with liberated FAs from adipose tissue. Liver mitochondria have the capacity to convert excess acetyl CoA, derived from fatty acid oxidation, into ketone bodies when the amount of Acetyl CoA exceeds oxidative capacity. These include acetoacetate, 3-hydroxybutyrate, and acetone. As ketone bodies are soluble, they can be transported in the blood to peripheral tissues where they can be reconverted into Acetyl CoA and oxidized in the TCA cycle. Production of Ketone Bodies During a fast, the liver is flooded with liberated FAs from adipose tissue. This inhibits pyruvate dehydrogenase in the TCA cycle and activates pyruvate carboxylase, shunting pyruvate towards OAA for transport out of the mitochondria and into gluconeogenesis. This leaves Acetyl CoA available for ketone body synthesis. Use of Ketone Bodies Ketone bodies are reconverted into acetyl CoA in the periphery, including brain, heart and muscle, although the liver cannot use them as fuel. Excessive Production of Ketone Bodies Excessive ketone production results in ketonemia and ketonuria, often observed in Type I diabetes. This results from high levels of fatty acid degradation and concomitant acetyl CoA synthesis. In diebetic individuals, urinary excretion can be as high as 5000 mg/d, and blood levels can go from 3 mg/dl (normal) to 90 mg/dl. Elevated ketone levels causes acidemia, as the pKa of the carboxyl group is 4. Excretion of glucose and ketone bodies also causes dehydration, and as a result, profound acidosis can occur. Ketoacidosis can also be the result of profound fasting. This information is for tr Continue reading >>

Regulation Of Ketone Body Production: Answer

Regulation Of Ketone Body Production: Answer

What regulates ketone body synthesis? The primary regulator of ketone body synthesis is fatty acid availability. When hormonal conditions (e.g., high glucagon, low insulin) cause fatty acid concentration in the plasma to be high, malonyl CoA concentration in the liver cytoplasm is low (because acetyl CoA carboxylase is in the less active phosphorylated state). Fatty acyl CoA can enter the mitochondria at a high rate (because there is no inhibition of CAT I), and beta-oxidation proceeds at a high rate. The ensuing high mitochondrial concentration of acetyl CoA results in active ketone body synthesis. 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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