Hepatic and duodenal drug metabolism in the rat during fat deficiency.

1. The effect of dietary fat deficiency on the composition of hepatic microsomes and postmitochondrial supernatant fraction of duodenal mucosa and on the activities of drug-metabolizing enzymes was studied in the rat. 2. There were only little changes in the measured protein, cholesterol and phospholipid fractions in the liver microsomes. In the postmitochondrial supernatant fraction of the duodenal mucosa, however, protein content was increased during fat deficiency. 3. In the fatty acid composition of hepatic microsomal phospholipids marked differences took place during fat deficiency. The amount of palmitoleic and eicosatrienoic acids increased from undetectable level to the amount of 6.9 and 9.5%. Also the amount of oleic acid was almost doubled and the content of linoleic and arachidonic acid was markedly decreased. 4. Fat deficiency was found to affect the drug metabolism both in the liver and small intestine. Only minor changes took place in the measured hydroxylative enzyme activities but the activity of UDPglucuronosyltransferase was highly depressed during fat deficiency both in the liver microsomes and in the postmitochondrial supernatant of duodenal mucosa. The changes in the UDPglucuronosyltransferase activity are concluded to be mediated via changes in the lipoidal environment of the enzyme in the membranes.