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

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