Immediate precursor of ketone bodies
Correct Answer: HMG - CoA
Description: KETONE BODY FORMATION IN LIVER (KETOGENESIS)Enzymes are mitochondrial:Steps1. Aceto-acetyl-CoA: Aceto-acetyl-CoA is the staing material for ketogenesis. This can arise in two ways:(a) Directly during the course of b-oxidation of fatty acids, or(b) As a result of condensation of two C-2 units, i.e. 'active acetate' (acetyl-CoA) by reversal of thiolase reaction.2. Formation of Acetoacetate: Acetoacetate is the first ketone body to be formed. This can occur in two ways:(a) By deacylation: Acetoacetate can be formed from aceto-acetyl-CoA by simple deacylation catalysed by the enzyme aceto-acetyl-CoA deacylase. The above does not seem to be the major pathway when excessive amount of ketone bodies are formed, the deacylation reaction is not enough to cope up.(b) Second pathway: Formation of acetoacetate intermediate production of "b-OH-b-methyl glutaryl CoA" (HMG-CoA). Present opinion ours the HMG-CoA pathway as the major route of ketone body formation.StepsInvolves two steps:* Condensation of aceto-acetyl-CoA with another molecule of acetyl-CoA to form b-OH-b methyl glutaryl-CoA (HMG-CoA) catalysed by the enzyme HMG-CoA synthase (mitochondrial enzyme).* HMG-CoA is then acted upon by another enzyme, HMG-CoA Lyase, which is also mitochondrial enzyme, to produce one molecule "acetoacetate" and one molecule of acetyl-CoANote* Both the enzymes HMG-CoA synthase and HMG-CoA Lyase are mitochondrial and must be available in mitocondrion for ketogenesis to occur.* Both the enzymes are present in liver cells mitochondria only.* A marked increase in activity of HMG-CoA Lyase has been noted in fasting.* HMG-CoA is a committed step. Cholesterol also can be formed by "HMG-CoA reductase".3. Formation of Acetone: As stated earlier, acetone is formed from acetoacetate by spontaneous decarboxylation (Non-enzymatic). Fig. 25.9: Formation, utilisation, and excretion of ketone bodies4. Formation of b-OH Butyrate: Acetoacetate once formed is conveed to b-OH-butyric acid; the reaction is catalysed by the enzyme b-OH-butyrate dehydrogenase, which is present in liver and also found in many other tissues. b-OH-butyrate is quantitatively the predominant ketone body present in blood and urine in KetosisRef: Textbook of Medical Biochemistry 8th Edition Dr (Brig) MN Chatterjea, Rana Shinde page no 425,426
Category:
Biochemistry
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