The Glucose/Glucose‐6‐Phosphate Cycle in the Periportal and Perivenous Zone of Rat Liver

Abstract

Periportal and perivenous hepatocytes contain different activities ( V ) of antagonistic key enzymes such as glucokinase and glucose-6-phosphatase. In order to get an insight into the metabolism of the periportal and perivenous area the flux rates (v) of the glucose/glucose-6-phosphate cycle were calculated on the basis of the Michaelis-Menten equation using the measured zonal concentrations of glucose and glucose 6-phosphate, the zonal activities of glucokinase and glucose-6-phosphatase previously reported and the half-saturating substrate concentrations (K,) of the two enzymes found in the literature. The concentrations of glucose were obtained as a first approximation by measuring the concentrations in portal (= periportal) and hepatovenous (= perivenous) blood; those of glucose 6-phosphate were calculated from the levels determined in microdissected periportal and perivenous liver tissue.The calculations showed (a) that the overall cycling rates agreed remarkably well with those reported for intact animals and (b) that during a normal feeding rhythm the periportal zone should catalyze net glucose output and the perivenous zone should mediate net glucose uptake, as proposed by the model of 'metabolic zonation'.Hepatocytes from the periportal (afferent) and perivenous (efferent) zone of the liver parenchyma differ in their enzyme equipments and subcellular structures [I, 21. This heterogeneity led to the model of 'metabolic zonation' [3,4]. It was proposed that the periportal hepatocytes, which are rich in glucose-6-phosphatase [5, 61, fructose-I ,6-bisphosphatase [7. 81 and phosphornolpyruvate carboxykinase [9], predominantly catalyze glucogenesis and that the perivenous cells, which are rich in glucokinase [7, 101 and pyruvate kinase [9], mainly mediate glycolysis.In the present investigation the cytosolic concentrations of glucose and of glucose-6-phosphate were measured in order to calculate the flux rates of the glucose/glucose-6-phosphate cycle in the periportal and perivenous zone of rat liver under different physiological conditions. The flux rates were to be determined using the measured zonal concentrations of glucose and glucose 6-phosphate, the zonal activities of glucokinase and glucose-6-phosphatase, as reported previously [5, 71, and the half-saturating substrate concentrations, as known from the literature [I 1 -151.It was found that the glucose concentrations in the periportal and perivenous zone were the same or formed a slight gradient depending on the metabolic situation, while the glucose-6-phosphate concentrations in the two zones were not significantly different under various conditions. Calculation of the flux rates revealed that normally the periportal zone

Regulation of peripheral insulin/glucagon levels by rat liver

“…By allowing 45 min of narcosis before taking blood samples [37], the handling stress had faded as indicated by two observations. (a) Peripheral adrenaline and noradrenaline levels had returned to low normal values [35] of 0.7 nM and 1.0 nM, respectively, after 35 min of narcosis (data not shown).…”

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

“…Hepatocytes from the periportal zone of the liver have different enzyme activities from the perivenous zone. 42 It has been shown that the periportal zone has relatively high gluconeogenesis rate since the zone is rich in enzyme activities such as glu cose-6-phosphatase, fructose 1,6 bisphosphatase and phosphoenolpyruvate carboxykinase, while the peri venous zone is rich in glycolytic enzyme activities such as pyruvate kinase and glucokinase. During the absorptive phase, the perivenous cells take up glucose from the blood and convert it into glycogen and lac tate.…”

Modulation by oxygen of the glucagon‐dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures

“…The perivenous cells are rich in the glucose-utilizing enzymes glucokinase [7,13,141 and pyruvate kinase L [9,15]. Evidence that the periportal cells are predominantly gluconeogenic and the perivenous cells glycolytic comes from studies in vivo and in vitro: zonal flux differences were calculated from enzyme and metabolite distributions measured in vivo [16]. They were observed in periportal-like and perivenous-like hepatocytes in Correspondence to K. Jungermann [18,191.…”