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JBC, Vol. 250, Issue 7, 2502-2509, Apr, 1975
M. S. Brown, G. Y. Brunschede and J. L. Goldstein
Microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase prepared from
either rat liver or human fibroblasts was shown to be inactivated in vitro
by a factor in extracts of cultured human fibroblasts in a reaction
requiring ATP or ADP and Mg2+ or Mn2+. The inactivation factor was found in
the soluble fraction of fibroblasts extracts and was shown to be
heat-labile, nondialyzable, and precipitable with ammonium sulfate. The
inactivation reaction was prevented by the addition of either an
ATP-regenerating system or an ADP-regenerating system, suggesting that the
presence of both adenine nucleotides may be required. A series of kinetic
experiments suggested that the fibroblast inactivation factor catalyzes the
conversion of the microsomal enzyme from an active to an inactive form. The
finding that solubilized preparations of 3-hydroxy-3-methylglutaryl
coenzyme A reductase from both rat liver and human fibroblasts were
resistant to inactivation raises the possibility that some unidentified
microsomal component also may participate in the inactivation reaction.
Inactivation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in vitro. An adenine nucleotide-dependent reaction catalyzed by a factor in human fibroblasts
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