Functional heterogeneity of periportal and perivenous hepatocytes.

Periportal and perivenous hepatocytes differ in their content of many key enzymes and subcellular structures. The cells also receive different regulatory signals due to the gradients established during liver passage of oxygen, substrates and hormones. The signal heterogeneity is important not only for short-term regulation of metabolism but also for long-term control, i.e. the induction of liver cell heterogeneity. The zonal heterogeneity changes upon longer lasting physiological and pathological alterations of the metabolic situation such as starvation, diabetes or regeneration after partial hepatectomy; it develops only gradually during the first weeks of postnatal life. The model of 'metabolic zonation' proposes a functional specialization for the two zones: in the periportal zone oxidative energy metabolism with beta-oxidation and amino acid metabolism, ureagenesis, gluconeogenesis, cholesterol synthesis, bile formation and oxidation protection are the predominant activities, and in the perivenous zone glycolysis, liponeogenesis, ketogenesis, glutamine formation and biotransformation are the prevalent processes.