Journal of Lipid Research, Vol 23, 105-113, Copyright © 1982 by Lipid Research, Inc.
3-hydroxy-3-methylglutaryl coenzyme A reductase from rat intestine: subcellular localization and in vitro regulation
FJ Field, SK Erickson, MA Shrewsbury and AD Cooper
The subcellular localization of 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase in rat intestine was reinvestigated. Highly enriched
fractions of endoplasmic reticulum and mitochondria were prepared from
mucosal cells. The highest specific activity of HMG-CoA reductase was
located in the endoplasmic reticulum fraction with recovery of 25% of the
total activity. The mitochondria had low specific activity and low recovery
of reductase activity relative to whole homogenate (2-5%). Despite attempts
to maximize cell lysis, much of the activity (about 60%) was recovered in a
low speed pellet which consisted of whole cells, nuclei, and cell debris as
determined by light microscopy. Taken together, the evidence strongly
suggests that much of the cellular HMG-CoA reductase activity is present in
the endoplasmic reticulum fraction and that mitochondria have little or no
intrinsic HMG-CoA reductase. The in vitro regulation of intestinal
microsomal HMG-CoA reductase was studied. The intestine possesses a
cytosolic HMG-CoA reductase kinase-phosphatase system which appears to be
closely related to that present in the liver. Intestinal reductase activity
in microsomes prepared from whole mucosal scrapings was inhibited 40-50% by
the presence of 50 mM NaF in the homogenizing buffer. It was less
susceptible to the action of the kinase than liver reductase. The effects
of NaF were reversed by incubation with partially purified intestinal or
liver phosphatases. These results suggest that the kinase-phosphatase
system could play a role in the regulation of intestinal sterol and
isoprene synthesis in vivo.
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