Ketogenesis regulation

Figure 22-9. Regulation of ketogenesis. -(Dshow three crucial steps in the pathway of metabolism of free fatty adds (FFA) that determine the magnitude of ketogenesis. (CPT-I, carnitine palmitoyltransferase-l.)...

Ketogenesis is regulated at three cmcial steps (1) control of free fatty acid mobihzation from adipose tissue (2) the activity of carnitine palmitoyltransferase-1 in hver, which determines the proportion of the fatty acid flux that is oxidized rather than esteri-fied and (3) partition of acetyl-CoA between the pathway of ketogenesis and the citric acid cycle. 

Mayes PA, Laker ME Regulation of ketogenesis in the liver. Biochem Soc Trans 1981 9 339. 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

These contribute to a marked decrease in oxidation. This is physiologically important since insulin is the only inhibitory hormone. The major hormone regulating ketogenesis is the other important hormone regulating... 

McGarry, J. D., Mannaerts, G. P., and Foster, D. W. 1977. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J. Clin. Invest. 60 265-270. 

Ferre, P Satabin, R, Dccaus, ).-R, Escriva, F., and Girard,. (1983). Development and regulation of ketogenesis in hepatocytes isolated from newborn rats. Biochern. J. 214, 937-942. 

Ketogenesis in the liver. All reactions occur in mitochondria the rate-controlling reactions (not shown) are release of fatty acids from adipose tissue and uptake of acyl-CoA into mitochondria, in particular, the CPTI reaction (see Figure 18-1). Acetoacetyl-CoA may regulate ketogenesis by inhibiting the transferase and the synthase. 

THE KETONE BODIES Most of the acetyl-CoA produced during fatty acid oxidation is used by the citric acid cycle or in isoprenoid synthesis (Section 12.3). Under normal conditions, fatty acid metabolism is so carefully regulated that only small amounts of excess acetyl-CoA are produced. In a process called ketogenesis, acetyl-CoA molecules are converted to acetoacetate, /3-hydroxybutyrate, and acetone, a group of molecules called the ketone bodies (Figure 12.7). 

Enzymatic regulation of liver acetyl-CoA metabolism in relation to ketogenesis, O. Wieland, L. Weiss, and I. Eger-Neufeldt, 1964, Adv. Enzyme Reg., 8599. 

Woifrum, C., Asiimaz, E., Luca, E., Friedman, J. M., and Stoffel, M. Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature 432 (2004) 1027-1032. 

Additional information <2, 6> (<6> enzyme functions as a metabolic sensor that monitors cellular AMP and ATP levels [31] <2> phosphory-lates key target proteins that control flux through metabolic pathways of hepatic ketogenesis, cholesterol synthesis, adipocyte lipolysis and skeletal muscle fatty acid oxidation [30] <4> regulates triacylglycerolsynthesis and fatty acid oxidation in liver and muscle reciprocally [29]) [29-31]... 

Grantham, B.D. Zammit, V.A. (1988) Biochem J249, 409-414 Role of carnitine palmitoyltransferase I in the regulation of hepatic ketogenesis during the onset and reversal of chronic diabetes. 

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