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

  title={Hemin-mediated oxidative inactivation of 3-hydroxy-3-methylglutaryl CoA reductase},
  author={S. Usha Devi and Tangirala Ramasarma},
  journal={Molecular and Cellular Biochemistry},
SummaryAddition 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 μM hemin, a maximum of about 50% inhibition was obtained in the case of the microsomal enzyme while the solubilized enzyme showed almost 80%6 inhibition. Dithiothreitol at high concentrations or either of the two… 
Preparation of a soluble 58kDa-3-hydroxy-3-methylglutaryl CoA reductase from liver microsomes and its inhibition by ethoxysilatrane, a hypocholesterolemic compound
On repeated thawing at room temperature of frozen preparations of heavy microsomes from rat livers, HMGCoA reductase activity was solubilized due to limited proteolysis and the extra region that links the active site domain to the membrane, present in the 58kDa-protein appears to be involved in mediating the inhibition by silatrane.
Investigations on the mechanism of the hypocholesterolemic action of 1-ethoxysilatrane
It is concluded that the hypocholesterolemic action of the compound rested entirely on the inhibition of cholesterol biosynthesis in vivo by inactivation of the rate-limiting enzyme HMGCoA reductase.
Evidence and nature of a novel thiol-oxidase in human platelets
It is proposed that the existence of this novel 47 kDa Thiol-oxidase within human platelets may provide a ‘crucial switch’ for the regulation of Receptor-‘C’k-dependent mevalonate pathway in human platelet cells.
Heme binding to Amyloid-β peptide: Mechanistic role in Alzheimer's disease
Evidence is provided for heme's key role in the important cytopathologies of AD, hypothesizing a functional deficiency for heME in the brains of AD patients, and a novel model of Abeta-induced heme-deficiency leading to mitochondrial dysfunction, AbETA-heme peroxidase, and altered metabolic activity is presented.


Hemin-mediated oxidative degradation of proteins.
Hemin-mediated oxidation of dithiothreitol reduces oxygen to H2O
These studies on the hemin-catalyzed oxidation of dithiothreitol provide a chemical model for a direct 4-electron reduction of O2 to H2O.
Sulfhydryl/disulfide forms of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Using radiation inactivation and immunoblotting techniques, evidence for functionally active forms of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase with molecular weights of about 100,000
Role of nonhemoglobin heme accumulation in the terminal differentiation of Friend erythroleukemia cells.
The combined results support the conclusion that both the DMSO treatment and the accumulation of excess heme are required to bring about the terminal differentiation of Friend erythroleukemia cells.
Tissue sulfhydryl groups.
  • G. Ellman
  • Chemistry
    Archives of biochemistry and biophysics
  • 1959