Lipogenesis regulation

SHORT- LONG-TERM MECHANISMS REGULATE LIPOGENESIS... 

Acetyl-CoA Carboxylase Is the Most Important Enzyme in the Regulation of Lipogenesis... 

Insulin Also Regulates Lipogenesis by Other Mechanisms... 

Lipogenesis is regulated at the acetyl-CoA carboxylase step by allosteric modifiers, phosphorylation/de-phosphorylation, and induction and repression of enzyme synthesis. Citrate activates the enzyme, and long-chain acyl-CoA inhibits its activity. Insulin activates acetyl-CoA carboxylase whereas glucagon and epinephrine have opposite actions. 

In additon to the central role of endocannabinoids in the regulation of feeding behaviour, a peripheral role has also been described. Gomez and coworkers [360] reported that food deprivation produced a 7-fold reduction in (1) levels in the small intestine of rats, but not in the brain or stomach. Intestinal (1) levels returned to normal when feeding resumed. The authors also showed that peripheral, but not central administration of (382) reduced food intake. The endocannabinoid system has also been reported to regulate peripheral lipogenesis [361]. 

Veech, R.L. (2003) A humble hexose monophosphate pathway metabolite regulates short- and long-term control of lipogenesis. Proc. Natl. Acad. Sci. USA 100, 5578-5580. 

Williamson, D.H., Munday, M.R., Jones, R.G., Roberts, A.F., Ramsey, A.J. 1983. Short-term dietary regulation of lipogenesis in the lactating mammary gland of the rat. Adv. Enzyme Regul. 21, 135-145. 

Regulation of Pyruvate Dehydrogenase Activity Pyruvate dehydrogenase is the key enzyme that commits pyruvate (and hence the products of carbohydrate metabolism) to complete oxidation (via the tricarboxyUc acid cycle) or lipogenesis. It is subject to regulation by both product inhibition and a phosphorylation/dephosphorylation mechanism. Acetyl CoA and NADH are both inhibitors, competing with coenzyme A and NAD+. 

MetabolicaUy, biotin is of central importance in lipogenesis, gluconeogen-esis, and the catabolism of branched-chain (and other) amino acids. There are two well-characterized biotin-responsive inborn errors of metabolism, which are fatal if untreated holocarboxylase synthetase deficiency and biotinidase deficiency. In addition, biotin induces a number of enzymes, including glu-cokinase and other key enzymes of glycolysis. Biotinylation of histones may be important in regulation of the cell cycle. 

Lipogenesis, the synthesis of lipids from carbohydrate via acetyl-CoA, occurs almost exclusively in the liver cells and the fatty tissue, (s. fig. 3.9) According to lipid topogenesis (4), the enzymes involved in triglyceride and phospholipid synthesis are localized on the cytoplasmic surface of the endoplasmic reticulum. The level of hepatic synthesis is regulated primarily by the insulin-glucagon quotient, as described by R.H. Unger in 1971. 

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