Interrelationships between 3-hydroxy-3-methylglutaryl-CoA synthase, acetoacetyl-CoA and ketogenesis.
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| Abstract |
Kinetic and physical approaches have been employed to investigate the binding of acetoacetyl-CoA to hydroxymethylglutaryl-CoA synthase. The enzyme has an apparent Km for acetoacetyl-CoA (0.35 microM) which is more than an order of magnitude lower than the Ki (6--10 microM) measured for substrate inhibition by this metabolite. Hepatic acetoacetyl-CoA concentration, as measured by a sensitive and highly specific radioactive assay appears to be in the 1--10 microM range; the concentration decreases during diabetic ketoacidosis. Total hepatic activity of hydroxymethylglutaryl-CoA synthase and levels of mitochondrial enzyme protein, determined by radioimmunoassay, are not appreciably different in livers from control or ketoacidotic animals. In contrast to the decrease in hepatic acetoacetyl-CoA concentration observed during ketoacidosis, myocardial acetoacetyl-CoA levels are increased by at least tenfold when compared to controls. Elevated acetoacetyl-CoA levels may serve to inhibit fatty acid utilization by the heart. Thus, a consideration of the multiple interactions of acetoacetyl-CoA with the enzymes involved in ketone body production and utilization may be useful in evaluating the metabolic significance of this intermediate.
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| Authors | L A Menahan, W T Hron, D G Hinkelman, H M Miziorko |
| Journal | European journal of biochemistry (Eur J Biochem) Vol. 119 Issue 2 Pg. 287-94 (Oct 1981) ISSN: 0014-2956 [Print] England |
| PMID | 6118268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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