576 2. ANALOGS OF ENZYME REACTION COMPONENTS 



cholera where alanine and aspartate accumulate when growth is suppressed 

 55% by 0.53 vciM deoxypyridoxol (Chatterjee and Haider, 1960). Perhaps 

 the first pyridoxine analogs to be recognized as inhibitors of bacterial growth 

 were the tellurium compounds studied by Morgan, Cooper, and their col- 

 leagues between 1923 and 1926. Gulland and Farrar (1944) postulated that 

 2,4-dimethyl-c^c^o-telluropentane-3,5-dione is toxic because of its structural 

 similarity to pyridoxine, but no further work or attempts to counteract the 

 inhibition with pyridoxine have come to my attention. An in vivo effect on 

 bacteria has been demonstrated in at least one case for deoxypyridoxol, 

 which prolonged the survival time of mice infected with Toxoplasma gondii 

 from 5 days to 12.1 days when it was incorported into the diet at 0.1%, 

 although some toxic symptoms were noted (Summers, 1957). Pyridoxine, 

 can counteract both the beneficial and toxic effects. 



Chick embryogenesis is disturbed by deoxypyridoxol and other analogs. 

 When 1 mg of deoxypyridoxol is injected into eggs, there is 100% mortality 

 of the embryos and this can be prevented by injecting pyridoxine (Cravens 

 and Snell, 1949). However, after 4 or more days the embryos become less 

 sensitive, and although higher doses are toxic they are not counteracted 

 by pyridoxine. Similar effects are noted for 4-methoxymethylpyridoxol but 

 it is at least 25 times more toxic than deoxypyridoxol to the early chick 

 embryo (Karnofsky et al., 1950). Mammalian fetal development is also dis- 

 turbed by deoxypyridoxol — fetuses resorbed, still-births, and abnormal 

 young — but administration of estrone and progesterone together prevents 

 these effects and pregnancy is maintained in the majority of the animals, 

 indicating that the action of the analog is primarily on the maternal tissues 

 rather than the embryo (Nelson, 1955). 



Some of the observations relative to the inhibition of tumor growth by 

 deoxypyridoxol will be summarized since these effects are interesting in 

 light of the fairly rapid amino acid metabolism in tumors and the generally 

 low levels of the Bg vitamers in solid tumors. Regression of mouse lympho- 

 sarcoma implants with deoxypyridoxol was achieved by Stoerk (1947, 1950) 

 when the animals were on a low-pyridoxine diet, but there was also loss 

 of body weight, suggesting an insufficiently specific inhibition. The fre- 

 quency of successful fibrosarcoma implants in rats is increased by pyri- 

 doxol and decreased by deoxypyridoxol, even though in the latter case no 

 severe deficiency symptoms are observed (Loefer, 1951). On the basis of 

 these findings, Gellhorn and Jones (1949) gave deoxypyridoxol to patients 

 with disseminated lymphosarcoma and acute leukemia in combination with 

 a pyridoxine-deficient diet. Although there was some weight loss and weak- 

 ness, there were no specific signs of deficiency, no changes in tryptophan 

 metabolism, no hematopoietic depression, and no retardation in the growth 

 of lymphoid tissue, the results being clinically insignificant. Deoxypyridoxol 

 appears to be reasonably effective in suppressing mammary carcinoma in 



