Metabolic Zonation of Liver Parenchyma

Abstract

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.

A Distributed Model of Carbohydrate Transport and Metabolism in the Liver during Rest and High-Intensity Exercise

“…While substantial evidence exists that enzymes of the fatty acid metabolic pathways also exhibit distributed activities, 40,6 the analysis of enzymatic zonation presented here is strictly limited to the central carbohydrate pathways.…”

Sources of carbon for hepatic glycogen synthesis in the conscious dog.

“…Cycling of glucose to three-carbon units and back into glycogen could occur either within the individual hepatocyte or between different populations of hepatocytes. In regard to the latter possibility, the hepatic parenchyma displays a remarkable degree of zonal heterogeneity which has given rise to the concept of"metabolic zonation" (38). The perivenous cells have high glucokinase and pyruvate kinase activities, giving them the greater capacity for glycolysis and for synthesis ofglycogen by the direct pathway.…”

Hypoxia-Inducible Factor 2 Regulates Hepatic Lipid Metabolism

“…This oxygen gradient is important for the zonation of metabolic activity in the liver. Because oxygen is an essential electron acceptor for oxidative metabolism, hepatocytes that perform glucose or fatty acid oxidation are located in the aerobic periportal zone, whereas oxygen-independent metabolic functions such as glucose uptake, glycolysis, and fatty acid synthesis are predominately performed by perivenous hepatocytes (16). Patients who experience perivenous hypoxia as a result of heart failure, obstructive sleep apnea, or excessive alcohol use can develop chronic liver injury characterized by steatosis and inflammation (17).…”