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Hemin-mediated oxidative inactivation of 3-hydroxy-3-methylglutaryl CoA reductase

Devi, Usha S and Ramasarma, T (1987) Hemin-mediated oxidative inactivation of 3-hydroxy-3-methylglutaryl CoA reductase. In: Molecular and Cellular Biochemistry, 77 (2). pp. 103-110.

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Abstract

Addition of hemoglobin, methemoglobin, hemin or hematin in the assay mixture of rat liver 3-hydroxy-3-methylglutaryl CoA (HMGCoA) reductase inhibited the activity of the enzyme. The inhibition by hemin was rapid, without any apparent dependence on time of preincubation. At $20\mu M$ hemin, a maximum of about 50% inhibition was obtained in the case of the microsomal enzyme while the solubilized enzyme showed almost 80% inhibition. Dithiothreitol at high concentrations or either of the two substrates of the enzyme (HMGCoA and NADPH) could afford partial protection when added before hemin. The $K_m$ for both the substrates increased in the presence of hemin. The inhibition by hemin appeared to be irreversible, the presence of KCN or $NaN_3$ being the only means of preventing the inhibition. Molecular oxygen was required for the inhibition. Oxygen radicals and $H_20_2$, however, did not seem to be involved. This offered a clue that an oxidation reaction of the reductase protein may be the likely mechanism of its inactivation. The enzyme protein did not, however, get degraded under the conditions of inhibition.

Item Type: Journal Article
Publication: Molecular and Cellular Biochemistry
Publisher: Springer Netherlands
Additional Information: Copyright of this article belongs to Springer.
Keywords: HMGCoA reductase;hemin;oxidative inactivation.
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 01 Apr 2008
Last Modified: 22 Oct 2010 09:38
URI: http://eprints.iisc.ac.in/id/eprint/13632

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