Fe2+-dependent modulation of 3-hydroxy-3-methylglutaryl CoA reductase by a cytosolic protein, fermodulin
Menon, A.S.; Devi, S.U.; Ramasarma, T.
Indian Journal of Biochemistry and Biophysics 21(1): 27-38
1984
ISSN/ISBN: 0301-1208 PMID: 6490056 Document Number: 241306
Rapid inactivation of rat liver 3-hydroxy-3-methyl glutaryl CoA (HMGCoA) reductase occurred when microsomes were incubated with FeSO4 and the cytosolic fraction. The inhibitory effect was not due to any artificial loss of product or substrates. The extent of inhibition was dependent on the concentration of the cytosolic protein and not on time or temperature of incubation. The activity of the solubilized enzyme inhibited by the cytosolic protein and FeSO4, was restored on dialysis. This suggested that neither proteolysis nor covalent modification of the enzyme was involved in the inactivation. Transferrin and ferritin could not substitute for the cytosolic protein. HMGCoA reductase activity was also inhibited by Hb, peroxidase and heme in the absence of Fe2+. At non-saturating concentrations of cytosolic protein, NaHCO3 potentiated the inhibitory effect of Fe2+. The Fe2+-dependent inhibitor activity was also present in the liver microsomal fraction as well as in the cytosolic fractions of heart, kidney and brain. The inhibitor protein was partially purified from rat liver and was capable of binding Fe. It was named fermodulin.