Abstract
Ketone bodies become major body fuels during fasting and consumption of a high-fat,
low-carbohydrate (ketogenic) diet. Hyperketonemia is associated with potential health
benefits. Ketone body synthesis (ketogenesis) is the last recognizable step of lipid
energy metabolism, a pathway that links dietary lipids and adipose triglycerides to
the Krebs cycle and respiratory chain and has three highly regulated control points:
(1) adipocyte lipolysis, (2) mitochondrial fatty acids entry, controlled by the inhibition
of carnitine palmityl transferase I by malonyl coenzyme A (CoA) and (3) mitochondrial
3-hydroxy-3-methylglutaryl CoA synthase, which catalyzes the irreversible first step
of ketone body synthesis. Each step is suppressed by an elevated circulating insulin
level or insulin/glucagon ratio. The utilization of ketone bodies (ketolysis) also
determines circulating ketone body levels. Consideration of ketone body metabolism
reveals the mechanisms underlying the extreme fragility of dietary ketosis to carbohydrate
intake and highlights areas for further study.
Keywords
Abbreviations:
3HB, 3-hydroxybutyrate (), AcAc, acetoacetate (), ACC, acetyl CoA carboxylase (), AcCoA, acetyl coenzyme A (), CoA, Coenzyme A (), HMG, 3-hydroxy-3-methylglutarate (), HL, HMG-CoA lyase (), MCD, malonyl CoA decarboxylase (), MHS, mitochondrial HMG-CoA synthase (), SCOT, Succinyl-CoA: 3-ketoacid CoA transferase (), T2, mitochondrial AcAcCoA thiolase ()To read this article in full you will need to make a payment
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