Adaptive character of liver glucokinase

Abstract

1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.

Hepatic glucokinase activity and circulating insulin concentrations in two inbred mouse strains

“…Glucokinase (EC 2.7.1.2) is the principle glucose-phosphorylating enzyme in the liver parenchymal cells of many species and has properties that equip it to fulfil a unique role in the regulation of hepatic glucose utilization [1,2]. Most studies on the enzyme and its regulation have used the rat.…”

The topographical location and unique nature of a glucokinase associated with the Golgi apparatus of rat liver

“…The enzyme solubilized from the Golgi preparation did not cross-react with an antiserum prepared against cytoplasmic glucokinase and showed different affinity from the cytoplasmic enzyme for concanavalin A. In the diabetic and neonatal rat livers the activities of Golgi glucokinase were similar to those found in the adult animal, which is different from the cytoplasmic enzyme, which decreases to very low activity in the diabetic rat (see Niemeyer et al, 1975, for a review) and only normally first appears in the developing rat around the time of weaning from 16 days of age onwards (Walker & Holland, 1965). The latter observations suggest that the two glucokinase enzymes do not have the same metabolic role in the liver cell, even though they both have comparatively high Km values for glucose.…”

“…In addition to the well-established cytoplasmic glucokinase (EC 2.7.1.2) (Walker, 1966;Niemeyer et al, 1975), some glucokinase activity possessing different kinetic characteristics is associated with microsomal fractions prepared from rat liver (Berthillier et al, 1970;Berthillier & Got, 1972). Most of this activity could be recovered in a microsomal subfraction containing Golgi material prepared by zonal centrifugation (Berthillier et al, 1973).…”

Stability of hexokinases A, B and C and N-acetylglucosamine kinase in liver cells isolated from rats submitted to diabetes and several dietary conditions

“…From the work of several groups it is known that hexokinase D, 'glucokinase' (ATP: D-glucose 6-phosphotransferase, EC 2.7.1.2), is affected markedly in the whole liver by dietary and hormonal manipulations [for references see reviews by Niemeyer et al (1975) and by Weinhouse (1976)]. The variations in hexokinase D activities are the result of changes in the amount of enzyme protein, as recognized by immunotitration (Clark-Turri et al, 1974), and are related to the concentrations of the specific RNA (Spence, 1983).…”

“…Most workers have only measured the combined activity of hexokinases A, B and C by using the spectrophotometric assay method of Viniuela et al (1963), a procedure that has several limitations (Niemeyer & Ureta, 1972;Reyes & Cardenas, 1984). Although there is general agreement on the constancy of total high-affinity hexokinase activity in liver after dietary and hormonal treatments [for reviews see Niemeyer et al (1975) and Weinhouse (1976)], some authors have described variations in certain conditions. Thus Machiya & Hoyosa (1969) reported a decrease in hexokinase B activity in liver from diabetic rats; Pilkis (1970) reported an increase in the total activity of high-affinity hexokinases in the liver of hypophysectomized rats treated with thyroxine; and Wakelam et al (1979) similarly observed an increase in the liver of neonatal rats treated with triiodothyronine.…”