BIOSYNTHESIS OF L‐ASCORBIC ACID IN ANIMALS AND PLANTS

Feeding experiments. The first convincing evidence that L-ascorbic acid is formed from a hexose was provided by the experiments of Ray,S1 which showed that with excised pea embryos growing on a synthetic medium, hexose sugars increased the production of the vitamin. It is perhaps significant that with every kind of plant material examined, mglucose caused the formation of L-ascorbic acid, whereas the other naturally occurring D-aldohexoses have sometimes given negative results. Negative results were obtained with pentose sugars and sugars of L configuration such as L-sorbose, which in view of its close structural similarity to L-ascorbic acid might have been expected to serve as a precursor.'*26 In the rat the stimulation by the administration of hypnotic drugs of the excretion of L-ascorbic acid and mglucuronides suggested that the two might be linked to a common intermediate that might well be D-glucose. In general, however, the evidence for the formation of L-ascorbic acid from hexose sugars in either the plant or the animal was suggestive rather than conclusive. The hexose sugars are not only interconvertible but give rise to a variety of metabolites, among which the substances acting as precursors might be found. Uniformly labeled glucose fed to "chloretonized" rats" gave rise to L-ascorbic acid (in the urine) that was also uniformly labeled. This suggested that the carbon chain of mglucose was not broken before conversion to L-ascorbic acid or, if so, that the fragments were recombined without any major differential dilution effect. The experiments of Horowitz et al." and Horowitz and Ring,I2 in which D-glucose labeled in either C-1 or C-6 was fed to chloretonized rats, giving rise to L-ascorbic acid predominantly labeled in C-6 or C-1 positions respectively, confirmed the suggestion that the molecule was not split. A repetition of these experiments with undrugged rats3 gave essentially similar results although the yield of L-ascorbic acid was less. In studies on the over-all conversion of D-glucose to L-ascorbic acid in the detached ripening strawberry and in the etiolated, germinating, cress seedling,20 injection or feeding of &glucose labeled on C-1 gave L-ascorbic with the label chiefly on C-1 (carboxyl) of the L-ascorbic acid. The six-carbon chain of the glucose was conserved, but it was clear that if this evidence were correct the synthesis from D-glucose to L-ascorbic acid must proceed by a pathway that was different from that in the rat. There was no inversion of the carbon chain since the L-ascorbic acid isolated was predominantly labeled on c-1. This work will be considered in greater detail later in this paper, the important fact being that the synthesis of L-ascorbic acid occurs from D-glucose without breaking the carbon chain.