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Phosphorylation and modulation of enzymic activity of native and protease cleaved purified hepatic 3-hydrox-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase by a calcium, calmodulin-dependent kinase

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6285995
; ;

The synthesis of cholesterol and other polyisoprenoid compounds is regulated by the rate limiting enzyme, HMG-CoA reductase (HMGR). A CaS , calmodulin-dependent kinase (CMK) has been purified which catalyzed the phosphorylation and concomitant inactivation of both native and purified HMGR. This low molecular weight brain cytosolic CMK phosphorylates histone H1, synapsin 1 and purified HMGR as major substrates. The kinase, purified by sequential chromatography on DEAE cellulose, calmodulin-affinity resin, and HPLC is an electrophoretically homogeneous protein of approximately 110,000 da. The molecular weight of the holoenzyme, substrate specificity, subunit protein composition, subunit autophosphorylation and subunit isoelectric points suggest that this kinase is different from other previously reported CMK's. Maximal phosphorylation of purified HMGR revealed a stoichiometry of one mole of phosphate/mole of M/sub r/ 1,000,000 da. Dephosphorylation of phosphorylated and inactivated native and purified HMGR revealed a time-dependent loss of TSP-bound radioactivity and reactivation of enzyme activity. Based on the results reported here, they propose that HMGR activity may be modulated by yet another kinase system involving covalent phosphorylation. The elucidation of a CMK-mediated modulation of HMGR activity may provide new insights into the molecular mechanisms involved in the regulation of cholesterol biosynthesis.

Research Organization:
NIH Bethesda, MD
OSTI ID:
6285995
Report Number(s):
CONF-870644-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BODY
CALCIUM COMPOUNDS
CHEMICAL REACTIONS
CHOLESTEROL
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
FRACTIONATION
GLANDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MOLECULAR WEIGHT
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RADIOISOTOPES
REACTION KINETICS
SEPARATION PROCESSES
STEROIDS
STEROLS
STOICHIOMETRY
SYNTHESIS
TIME DEPENDENCE
TRACER TECHNIQUES
TRANSFERASES