IV. BIOCHEMICAL SYSTEMS 343 



of the great variety of organisms which require inositol, virtually nothing 

 is knowTi of the function of the vitamin in terms of enzymes or coenzymes. 

 Since animals probably can synthesize m?/o-inositol (see Section VI), it 

 has been assumed that the dietary requirement of this compound reflects 

 a requirement of the intestinal flora. Woolley^^ found that feeding panto- 

 thenic acid benefited mice deficient in inositol. White rats do not require 

 myo-inositol when fed purified diets,^^' ^^ but Cunha et al.^ found that rats 

 on diets containing soybean meal showed poor growth and hair loss. These 

 symptoms lessened after feeding of inositol. The fact that biotin or the 

 sulfur-containing amino acids can prevent the deficiency symptoms^^ lends 

 support to the hypothesis that the beneficial effect of inositol is indirect 

 and is probably exerted through intestinal microorganisms. 



1. Studies with Inhibitory Analogs 



The possibility that the insecticide, hexachlorocyclohexane, exerts its 

 physiological action by antagonizing a normal function of m?/o-inositol 

 was first suggested by Slade.^* Evidence tending to support this possibility 

 has been obtained •with several inositol-requiring microorganisms. ^^"-^ For 

 example, Kirkwood and Phillips^^ found the y isomer of hexachlorocyclo- 

 hexane to inhibit growth of an inositol-requiring strain of Saccharomyces 

 cerevisiae. The inhibitory effect was competitively, but incompletely, re- 

 versed by m?/o-inositol. The 5, a, and /3 isomers, in decreasing order, were 

 not as strongly inhibitory as the 7 isomer, and their effects were not in- 

 fluenced by increasing concentrations of myo-inositol. The relatively low 

 inhibition index,^- indicating a close similarity of structure between the 

 inhibitor and metabolite, was taken by Kirkwood and Phillips^ ^ to indicate 

 that the y isomer of hexachlorocyclohexane had the same configuration as 

 myo-inositol. Bijvoet^* and coworkers^^ as well as Blekkingh^^ conclude from 

 physical measurements that the 7 isomer does not have the configuration 

 of m;/o-inositol but appears to have that of wi^co-inositol. Dissimilarity of 

 configuration between the 7 isomer and m?/o-inositol introduces complica- 



" D. W. WooUey, J. Exptl. Med. 75, 277 (1942). 



16 T. H. Jukes, Proc. Soc. Exptl. Biol. Med. 45, 625 (1940). 



'* L. R. Richardson, A. G. Hogan, B. Long, and K. I. Itschner, Proc. Soc. Exptl. 



Biol. Med. iQ, 530 (1941). 

 1^ R. R. Spitzer and P. H. Phillips, Proc. Soc. Exptl. Biol. Med. 63, 10 (1946). 

 18 R. E. Slade, Chemistry & Industry 64, 314 (1945). 

 1" S. Kirkwood and P. H. Phillips, /. Biol. Chem. 163, 251 (1946). 

 20 H. W. Buston, S. E. Jacobs, and A. Goldstein, Nature 158, 22 (1946). 

 2' R. C. Fuller, R. W. Barratt, and E. L. Tatum, J. Biol. Chem. 186, 823 (1940). 

 22 H. Mcllwain, Brit. J. Exptl. Pathol. 23, 95 (1942). 

 " J. M. Bijvoet, Rec. trav. chim. 67, 777 (1948). 

 " G. W. Von Vloten, C. A. Kruissink, B. Strijk, and J. M. Bijvoet, Nature 162, 771 



(1948). 

 " J. J. A. Blekkingh, Rec. trav. chim. 68, 345 (1949). 



