Functional significance of hepatocyte heterogeneity for glycolysis and gluconeogenesis.

Hepatocytes from the periportal (afferent) and perivenous (efferent) zone of the liver parenchyma differ in their enzyme distribution and subcellular structures. The key enzymes of gluconeogenesis are predominant in the periportal zone, those of glycolysis in the perivenous zone. The heterogeneous expression of the genome in hepatocytes is apparently caused by the periportal to perivenous gradient in oxygen- and hormone-concentrations as well as by a different autonomic innervation of the parenchymal zones. The model of "metabolic zonation" suggests that, in concordance with the distribution of the key enzymes, gluconeogenesis would be predominantly catalyzed by periportal hepatocytes, while glycolysis would be preferentially mediated by perivenous cells. This model is corroborated by a calculation of the flux at the glucose/glucose-6-phosphate cycle in vivo in the periportal and perivenous zone and by a determination of the glycolytic and gluconeogenic rate in "periportal" and "perivenous" hepatocytes induced in cell culture.