The biosynthesis of hyaluronic acid by group A Streptococcus. IV. Role of glucosone as an intermediate in the synthesis of glucosamine.

That glucosamine arises from glucose without previous scission of the carbon chain has been indicated by studies of the biosynthesis of the glucosamine portion of the hyaluronic acid (HA) molecule by group A streptococcus (1, 2) and of the formation of blood glucosamine in rats (3, 4). Relatively little information is available regarding the mechanism of this reaction, although Lowther and Rogers (5), in a preliminary report of studies utilizing resting suspensions of hemolytic streptococci, found evidence that glutamine or a mixture of glutamic acid and NHd+ is necessary for the synthesis of HA. More recently, Leloir and Cardini (6) found evidence that glucosamine-6-phosphate is formed by the reaction of the amide group of glutamine and glucose-6-phosphate in extracts of Neurospora crassa. Glucosone, because of its structural relationship to glucose, has been the subject of a variety of investigations regarding its possible relationship to the metabolism of glucose. The earlier literature regarding both biological and chemical studies of this compound has been reviewed in detail by Becker et a.!. (3, 4, 7, 8). Utilizing glucose-l-Cl4 and glucosone-l-Cl”, Becker and Day (3,4) found that a greater portion of the radioactivity of the glucosone than that of glucose is ‘converted to blood glucosamine in the rat and postulated that glucosbne is an intermediate in the synthesis of glucosamine. In a study of the biosynthesis of HA by group A streptococci, Topper and Lipton (2) observed that the addition of inactive glucosone to a medium containing glucose-l-C’4 resulted in a decrease in the labeling of the isolated hyaluronic acid and .concluded that, “The present findings suggest that the dicarbonyl compound may indeed lie in the reaction sequence: glucose to glucosone to glucosamine.?