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.
Restricted to Registered users only
Download (537Kb) | Request a copy
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|
|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|
Actions (login required)