Glucokinase and hexokinase in liver in relation to glycogen synthesis

Abstract

The first step in the pathway from glucose to glycogen has not yet been satisfactorily accounted for. The enzyme responsible for the phosphorylation o f glucose in liver has not been clearly identified. Qualitatively, Slein, Cori, and Cori (1) postulated a “glucokinase,” but Crane and Sols (2) reported the identification o f a hexokinase that apparently had a Michaelis constant (K,,,) for glucose not as low as those o f the hexokinases o f other tissues. Quantitatively, the finding by Long (3), in a survey o f glucose phosphorylation rates by homogenates o f rat organs, that liver was the least active o f all has been a long standing puzzle. An important advance was made recently by DiPietro, Sharma, and Weinhouse (4, 5) when they found that at a high glucose concentration, the glucose phosphorylation rate o f liver extracts approaches that required to account for glycogen synthesis from glucose in normal fed rats. Nevertheless, a major difficulty for the involvement o f hexokinase as the first step in the pathway o f glucose to glycogen in liver stems from the finding by Leloir et al. (6) that the liver UDP-glucose-glycogen glucosyltransferase (glycogen synthetase) is strongly dependent for activity on a rather high concentration o f glucose-&P, a strong inhibitor o f animal tissue hexokinases (2). Because o f these opposing ef fects o f glucose-6-P, hexokinase and glycogen synthetase would not be able to work efficiently in sequence. Figueroa, Pfeifer, and Niemeyer (7) have recently raised doubts as to whether glucose- 6-P is a necessary step in the synthesis o f glycogen from glucose in liver. We report h