Biochemical studies on inositol. III. Biosynthesis of inositol by yeast.

It is over a century since Scherer discovered in Liebig’s meat extract a hexahydroxycyclohexane which he named inositol (1). Since that time a number of similar compounds have been shown to occur in nature, and a few others have been synthesized in the laboratory. Of the nine possible stereoisomeric forms of hexahydroxycychlohexane, myo-inositol is by far the most widely distributed in nature and the one which has been implicated in the nutrition of animals and microorganisms (2, 3). It is because of its universal occurrence and its vitamin-like activity that inositol, among all other cyclitols, received the greatest attention by chemists and biochemists alike. Among the many interesting problems concerned with the chemistry and metabolism of inositol, the mechanism of its biosynthesis still remains in the realm of speculation and uncertainty. That plants can synthesize inositol was quite evident from the beginning, since plants have been the richest source of inositol. Work by many investigators has established the fact that a number of microorganisms are able to synthesize inositol (4-7). With regard to the ability of animals to synthesize inositol, progress was slower since Vohl in 1858 reported that the urine of a man with diabetes insipidus contained inositol in amounts far in excess of the amount that could be accounted for from the food intake. Similar observations were later reported by Needham (8)) and others (9,lO) have shown that glucoseCl* is incorporated into inositol in animals. In a thorough presentation, Fischer discussed the chemical and biological relationships between hexoses and inositols (11). He proposed, as a working hypothesis, that inositol might be synthesized directly from glucose or glucose phosphates by a cyclization reaction. The observations of Portmann, as related by Fischer, that sharks have large amounts of inositol in the muscles of their fins, but no glycogen or other reserve carbohydrate in the liver, prompted the belief that inositol, formed from glucose directly, could serve as a source of blood glucose by the reopening of the inositol ring. The successful cyclization of glucose to inositol by chemical means by