ANALOGS OF PYRIDOXAL 569 



pyridoxol must be reflected in depression of the activity of enzymes requir- 

 ing this coenzyme, but not necessarily in all equally. The failure of pyridox- 

 amine-P to fall as much as pyridoxal-P might indicate that transaminases 

 are not depleted as readily as other pyridoxal-P enzymes,-^ but interpreta- 

 tion is made difficult by the fact that we do not know what fractions of 

 these substances are bound to apoenzymes and to nonenzyme protein. The 

 effects on the tumors are similar but of less magnitude, and the changes in 

 pyridoxamine-P are again variable, even increasing in ascites tumor. The 

 rise in pyridoxal-P and total vitamers in ascites fluid may reflect the loss 

 of these substances from the cells. 



Effects of Deoxypyridoxol on Pyridoxal-P-Dependent Enzymes in Vivo 



The results reported on transaminase activity during administration of 

 deoxypyridoxol are variable. Transamination in hamster hearts is reduced 

 30-40% in animals with a dietary deficiency, but injecting deoxypyridoxol 

 at 50 //g per animal 3 times a week does not lower the activity further 

 (Shwartzman and Hift, 1951). However, there is some growth inhibition 

 beyond that shown in the deficient animals, although no specific symptoms 

 were noted. Deoxypyridoxol at 100 //g/day in rats does not alter the aspar- 

 tate-glutamate transaminase and actually seems to increase the alanine- 

 glutamate transaminase activity in liver compared to animals on a deficient 

 diet (Caldwell and McHenry, 1953). Since the animals receiving deoxypyri- 

 doxol had severe dermatitis, it was justifiably concluded that the production 

 of dermatitis is unrelated to liver transaminase. On the other hand, Dietrich 

 and Shapiro (1953 a) found a greater fall in liver transaminase when mice 

 were injected with deoxypyridoxol at 150 mg/kg/day than in simple dietary 

 deficiency ( — 49% and —37%, respectively). Indeed, transaminase levels 

 in several tissues fall very markedly in mice on 175 mg/kg/day of deoxy- 

 pyridoxol (Shapiro et al., 1953). There is not much difference in the rates 

 of decrease in the various tissues (Fig. 2-20). It is difficult to reconcile all 

 of these results unless it is a matter of species variation, which is unlikely. 

 Transaminases are not directly inhibited very potently by deoxypyridoxol; 

 the K^ is 0.12 m.M for the alanine-pyruvate transaminase of Pseudomonas, 

 for example (Dempsey and Snell, 1963). The very high inhibitory activity 

 of pyridoxyl-L-alanine {K, = 0.00018 mM) is surprising. 



The results on decarboxylases are similar. Dietary pyridoxine deficiency 

 causes a 50% fall in rat brain glutamate decarboxylase, but administering 

 deoxypyridoxol in addition produces no further depletion (Roberts et al., 

 1951). More recent studies, summarized in Table 2-37, clearly indicate a 

 lack of correlation between the brain decarboxylase levels and the occur- 

 rence of convulsions; e.g., 3-deoxy pyridoxol convulses without a significant 

 change in enzyme activity, whereas c/j-methylpyridoxol lowers the enzyme 

 level without producing convulsions. Liver dopa decarboxylase is decreased 



