Metabolic Zonation of Liver Parenchyma

Periportal and perivenous hepatocytes differ in their content of enzymes and subcellular structures and thus in their metabolic capacities. Therefore, the model of metabolic zonation proposes that: (1) periportal hepatocytes catalyze predominantly oxidative energy metabolism with beta-oxidation and amino acid catabolism as well as ureagenesis for glycogen synthesis and glucose release, bile formation with cholesterol synthesis and protective metabolism; and (2) perivenous hepatocytes mediate preferentially glucose uptake for glycogen synthesis, glycolysis, and liponeogenesis as well as ketogenesis, glutamine formation, and xenobiotic metabolism. Periportal and perivenous hepatocytes are under the control of a different input of humoral and nervous signals, because concentration gradients of oxygen, substrates, and hormones are established during passage of blood through the liver and because gradients of nerve densities seem to exist. In periportal and perivenous hepatocytes gene expression can be different due to the zonal gradients in oxygen and hormone concentrations as well as nerve densities. The functional specialization of periportal and perivenous hepatocytes has been demonstrated especially well for carbohydrate, amino acid and ammonia, and xenobiotic metabolism as well as for bile formation by different techniques: Calculation of metabolic rates based on the zonal distributions of enzymes and metabolites, measurements of rates in periportal-like and perivenous-like hepatocytes in cell culture and in hepatocyte populations enriched in periportal and perivenous cells as well as in perfused livers during orthograde and retrograde flow using standard methods and noninvasive techniques with surface microlight guides and miniature oxygen electrodes.