Role of intralobular compartmentation in hepatic metabolism.

The model of metabolic zonation is based on the finding that periportal and perivenous hepatocytes possess different activities and amounts of enzymes and thus different metabolic capacities. Periportal cells catalyze predominantly oxidative energy metabolism of fatty and amino acids, ureagenesis, glucose release and glycogen formation via gluconeogenesis, bile formation and protective metabolism. Perivenous hepatocytes carry out preferentially glucose uptake for glycogen synthesis, glycolysis coupled to liponeogenesis, glutamine formation and xenobiotic metabolism. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes has been characterized well for the metabolism of carbohydrates, amino acids, ammonia and xenobiotics as well as for the formation of bile. Zonal flux differences have been calculated based on the distributions of enzymes and metabolites, they have been observed in periportal-like and perivenous-like hepatocytes in cell culture and in periportal- and perivenous-enriched hepatocyte populations as well as in perfused livers during orthograde and retrograde flow. Oxygen and insulin/glucagon gradients could have a prominent role in the induction of zonation of carbohydrate- and cell-to-biomatrix interactions in that of ammonia-metabolizing enzymes.