In vivo studies of intrahepatic metabolic pathways

In vivo studies of liver metabolism have long been limited to measurement by the balance technique or isotope dilution method of the amounts of substrates taken up or produced by the liver. New methods, based mainly on the use of stable isotopes, now allow important data to be obtained on intrahepatic metabolic pathways. Nuclear magnetic resonance and chemical biopsy of glucuronic acid by acetaminophen facilitate the study of glycogen metabolism. Chemical biopsies of liver glutamine by phenylacetate and of cytosolic acetylCoA by sulfamethoxazole provide important data respectively on Krebs cycle activity and gluconeogenesis and on lipogenesis and cholesterol synthesis. Mass isotopomer distribution analysis of molecules synthesised during infusion of 13C-labelled precursors allows an estimation of in vivo gluconeogenesis as well as cholesterol synthesis and lipogenesis. Finally, these metabolic pathways can be studied through the incorporation of deuterium from deuterated water in glucose, fatty acids and cholesterol. All these non-invasive techniques allow investigations to be undertaken in human beings to study the nutritional and hormonal regulation of liver metabolism in normal subjects and in pathological situations.