IV. HIOCIIEMICAL SYSTEMS 215 



poiuliiiK tissues from control animals. The synthesis was greatest when the 

 tissues were supplied with a mixture of pyruvate, DL-glyceraldehyde, and 

 hexose diphosphate.-'' Mainioso, glucose, and 2-ketogulonic acid were in- 

 effective. 



The close link in animal and plant tissue between hexose sugars and 

 ascorbic acid has stimulated speculation as to the method by which the 

 transformation of one to the other is effected. A direct conversion of D-glu- 

 cose to L-ascorbic acid without breaking the carbon chain of the sugar in- 

 volves the inversion of the configuration of the groups in carbon atom 5. A 

 simple scheme based on known chemical and biochemical reactions can be 

 suggested, viz., D-glucose — ^ sorbitol — > L-sorbose — > 2-ketogulonic acid — > 

 L-ascorbic acid. 



L-Sorbose has lieen reported by one worker as a precursor of ascorbic 

 acid ,2* but this has not been substantiated by others." 



Neither sorbitol nor 2-keto-L-gulonic acid when supplied to seedlings 

 increased the amount of ascorbic acid synthesized.-^ The formation of ascor- 

 bic acid from 2-keto-L-gulonic acid has been reported to occur in Aspergil- 

 lus niger,-^ and methyl-2-keto-L-gulonate has been reported as having anti- 

 scorbutic acitivity,-^ though the free acid is inactive. 



The most direct evidence bearing on the synthesis of ascorbic acid from 

 glucose has been obtained by means of radioactive tracer technique. When 

 D-glucose, labeled uniformly in all positions, is fed to chloretone-treated 

 rats, it is followed by the excretion of ascorbic acid labeled uniformly in all 

 positions.^" The suggestion has been made that the carbon chain of D-glu- 

 cose is not broken before being converted into ascorbic acid, or that, if so, 

 the fragments are recombined without any major differential dilution effect. 



Two papers have recently appeared which throw considerable light on 

 the mechanism of synthesis. Using the radioactive tracer technique, Horo- 

 witz el al.^^ have shown that feeding of D-glucose labeled with C^"* at carbon 

 atom 1 produces L-ascorbic acid labeled only at position 6. Even more il- 

 luminating is the work of Isherwood et al.,^-^ who have shown that in both 

 plants and animals D-glucurono-7-lactone and L-gulono-7-lactone on the one 

 hand and D-galacturonic acid methyl ester and L-galactono-7-lactone on the 



" C. V. Smythe and C. G. King, J . Biol. ('hem. 142, 529 (1942). 



"G. V. Sztaneczy, Biochem. Z. 295, .369 (1938). 



" Y.-T. Chen, Ph.D. Thesis, Caml)ri{lge (1950). 



2« A. Gain, Ber. schwciz. hot. Ges. 56, 113 (1946). 



" T. Reichstein and V. Demole, Festschr. Emil Barell, Basel (1936); G. Lorenzini 



and .\. Corbellini, Arch. inst. biochem. Ital. 10, 131 (1938). 

 «» S. S. Jackel, E. H. Mosbach, J. J. Burns, and C. G. King, J. Biol. Chem. 186, 569 



(1950). 

 ^' H. H. Horowitz, A. P. Doerschuk, an<l C. G. King, J. Biol. Chem. 199, 193 (1952). 

 32» F. A. Isherwood, Y.-T. Chen, and L. W. Mapson, Nature 171, 348 (1953). 



