Triacylglycerol synthesis is enhanced by
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Insulin
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TG stores in the body is continually undergoing (a) Esterification (synthesis) and (b) Lipolysis (breakdown).These two processes are not the forward and reverse processes of the same reaction. They are entirely differentMany of the nutritional, metabolic and hormonal factors regulate either of these two mechanisms, i.e. esterification and lipolysis. Resultant of these two processes determine the magnitude of free fatty acid pool in adipose tissue and this, in turn, will determine the level of free fatty acid (FFA) circulating in the blood.I. Esterification (Synthesis of TG) In adipose tissue, for TG synthesis, two substrates are required:Acyl-CoAa-Glycero-PFor detailed steps, see the biosynthesis of TG.1. Sources of Acyl-CoASources of FFA in blood are:Dietary,Synthesis of FA (palmitic acid) from acetyl-CoA 'de novo' synthesis (extramitochondrial). Fuher elongation to form other fatty acids in microsomes.Acyl-CoA obtained from lipolysis taking place in adipose tissue (FFA-Pool No. 1).FFA obtained from lipolysis of TG of circulating chylomicrons and VLDL by lipoprotein lipase enzyme present in capillary wall (FFA-Pool No.2. Which are taken up by adipose tissue. 2. Source of a-Glycerol-PMainly two:Conversion of glycerol to a-Glycero-P by the enzyme Glycerokinase in presence of ATP.The other source is from glucose oxidation. Dihydroxyacetone-P is conveed to a-Glycero-P. The enzyme glycerol kinase is practically absent in adipose tissue. If any glycerokinase is present, it has verylow activity. Hence, glycerol produced by lipolysis in adipose tissue cannot be utilised for provision of a-Glycero-P and thus, glycerol passes into the blood,from where it is taken up by the liver, kidney and other tissues which possess glycerokinase and is utilised for gluconeogenesis. Thus, for provision of a-Glycero-P in adipose tissue for TG synthesis, the tissue is dependent on a supply of glucose and glycolysis.II. Lipolysis (Breakdown of TG)TG in adipose tissue undergoes hydrolysis by a hormone-sensitive TG lipase enzyme to form free fatty acids and glycerol.Adipolytic lipases are three:Hormone-sensitive triacyl glycerol lipase: Key regulating enzyme.Two others are not hormone-sensitive:Diacyl glycerol lipaseMonoacyl glycerol lipaseThese lipases are distinct from lipoprotein lipase that catalyses lipoprotein TG (Present in chylomicrons and VLDL) hydrolysis before it is taken up by extrahepatictissues. The free fatty acids formed by lipolysis can be reconveed in the tissue to acyl-CoA by Acyl-CoA synthase and re-esterified with a-Glycero-P to form TG. Thus, there is a continuous cycle of lipolysis and reesterification within the tissue. NoteWhen the rate of re-esterification is less than rate of lipolysis, FFA accumulates and diffuses into the plasma where it raises the level of FFA | in plasma.Effect of glucose: Under conditions of adequate nutritional intake or when utilisation of glucose by adipose tissue is increased, then more a-Glycero-P will be available. Re-esterification will be greater than lipolysis; as a result, FFA outflow decreases and plasma FFA| level falls. In vitro studies have shown that release of glycerolcontinues; that means lipolysis continues. Hence, effect of glucose in reducing plasma FFA level is not mediated by decreasing the rate of lipolysis. It proves that the effect is due to the provision of a-Glycero-P from glycolysis, which enhances esterification.Adipose tissue metabolism in diabetes mellitus and in starvation: In diabetes mellitus and in starvation,availability of glucose in adipose tissue is grossly reduced, resulting to lack of a-Glycero-P. Thus, the rate of re-esterification is decreased|. Lipolysis is greater thanre-esterification, resulting to the accumulation of FFA and increase in plasma FFA level.Ref: M.N. Chatterjee - Textbook of Biochemistry, 8th edition, page no: 400-402
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