Journal of Lipid Research, Vol 26, 47-53, Copyright © 1985 by Lipid Research, Inc.
3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in the human gastrointestinal tract
RL Gebhard, BG Stone and WF Prigge
Activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34)
was measured in intestinal mucosa of the human gastrointestinal tract.
Activity was highest in gastric mucosa (18.2 pmol per mg per min) and there
was a constant low level in the small bowel and colon (approximately 10
pmol per mg per min). Phosphorylation/dephosphorylation modulation of
intestinal reductase activity was demonstrated in normal mucosa. Expressed
jejunal reductase activity was significantly higher in celiac sprue mucosa
and mucosa from defunctionalized intestine of jejunoileal bypass patients.
Enzyme activity also increased during 24-hr mucosal organ culture in the
absence of exogenous cholesterol. Addition to the culture medium of pure
cholesterol or 25-hydroxycholesterol dissolved in a small volume of ethanol
suppressed the culture-induced increase to 86 +/- 3% and 69 +/- 5% of
paired controls, respectively. This evidence suggests that a moderate
degree of feedback regulation of intestinal cholesterol synthesis by
luminal sterol occurs in man. Mucosal HMG-CoA reductase activity was also
measured in patients with hyperlipoproteinemia. Patients with either
predominant hypercholesterolemia or predominant hypertriglyceridemia lipid
profiles had "normal" expressed reductase activity, but feedback regulation
by free cholesterol could not be demonstrated in either group under these
conditions.
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