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Regulation of ketogenesis. Mitochondrial acetyl-CoA acetyltransferase from rat liver: initial-rate kinetics in the presence of the product CoASH reveal intermediary plateau regions.
- Source :
-
European journal of biochemistry [Eur J Biochem] 1982 Nov 15; Vol. 128 (2-3), pp. 413-9. - Publication Year :
- 1982
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Abstract
- The analysis of the initial-rate kinetics of the liver mitochondrial acetyl-CoA acetyltransferase (acetoacetyl-CoA thiolase) in the direction of acetoacetyl-CoA synthesis under product inhibition was performed. 1. Acetyl-CoA acetyltransferase shows a hyperbolic response of reaction velocity to changes in acetyl-CoA concentrations with an apparent Km of 0.237 +/- 0.001 mM. 2. CoASH is a (non-competitive) product inhibitor with a Kis of 22.6 microM and shifts the apparent Km for acetyl-CoA to the physiological concentration of this substrate in mitochondria (S0.5 = 1.12 mM in the presence of 121 microM CoASH). 3. CoASH causes a transformation of the Michaelis-Menten kinetics into initial-rate kinetics with four intermediary plateau regions. 4. The product analogue desulpho-CoA triggers a negative cooperativity as to the dependence of the reaction velocity on the acetyl-CoA concentration. These product effects drastically desensitize the acetyl-CoA acetyltransferase in its reaction velocity response to the acetyl-CoA concentrations and simultaneously extend the substrate dependence range. Thus a control of acetoacetyl-CoA synthesis by the substrate is established over the physiological acetyl-CoA concentration range. We suggest that this control mechanism is the key in establishing the rates of ketogenesis.
Details
- Language :
- English
- ISSN :
- 0014-2956
- Volume :
- 128
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- European journal of biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 6129974