NEW METHODS FOR IN-VIVO STUDIES OF HEPATIC-METABOLISM

In vivo studies of liver metabolism have been limited for a long time to measurements, by the balance technique or the isotope dilution meth od, of the amounts of substrates taken up or produced by liver. New me thods have been developed that now permit us to obtain important infor mation on intrahepatic metabolic pathways. Nuclear magnetic resonance permits noninvasive studies of liver glycogen synthesis and breakdown. Chemical biopsy of glucuronic acid by acetaminophen also permits the study of glycogen synthesis whereas chemical biopsies of liver glutami ne by phenylacetate and of cytosolic acetyl-CoA by sulfamethoxazole gi ve important information concerning, respectively, Krebs cycle activit y and gluconeogenesis and on lipogenesis and cholesterol synthesis. Ma ss isotopomer distribution analysis of molecules synthesized during th e infusion of a deuterium or C-13-labeled precursor permits the estima tion of in vivo gluconeogenesis as well as cholesterol synthesis and l ipogenesis. Finally, these metabolic pathways can be studied through t he incorporation of deuterium from deuterated water in glucose, fatty acids and cholesterol. All these noninvasive techniques will allow inv estigations to be undertaken in humans, addressing the nutritional and hormonal regulation of liver metabolism in normal subjects and in pat hological situations.