ANALOGS OF PYRIDOXAL 567 



section, but there is now sufficient evidence that the activities of certain 

 pyridoxal-P-dependent enzymes are reduced. 



„ .J . -p. J 1 Liver vitamin Br 



ryndoxine JJeoxypyridoxol 



(/'g/g) 



- - 6.3 

 + - 11.0 



- + 6.3 



+ + 9.6 



Interpretation of this apparent discrepancy between toxic reactions and 

 insignificant changes in liver vitamin Bg during deoxypyridoxol treatment 

 can be made along several lines. In the first place, it is generally believed 

 that much of the tissue pyridoxal is bound to nonenzyme protein, possibly 

 in part through the aldehyde group, so that analyses of total tissue levels 

 do not necessarily reflect changes in coenzyme concentration. The fact that 

 enzyme activity is often depressed without significant changes in total vi- 

 tamin Bg suggests that this can be an explanation. That bound to nonen- 

 zyme protein may not be displaced by deoxypyridoxol since this analog 

 contains no aldehyde group. In the second place, analyses have been made 

 only in the liver and it is unlikely that changes in liver pyridoxal function 

 are responsible for any of the common toxic symptoms of deficiency. It is 

 even possible that during treatment with deoxypyridoxol there is a transfer 

 of vitamin Bg substances from one tissue to another. It is conceivable that 

 deoxypyridoxol has actions other than interference with pyridoxal function, 

 but the fact that its toxicity can be reduced by pyridoxine administration 

 points to a close relationship between its effects and pyridoxal. I think 

 that more emphasis must be placed on the changes in enzyme activity 

 rather than on the tissue levels of vitamin Bg for the reasons given above. 



The most complete investigation of the effects of deoxypyridoxol on the 

 concentrations of tissue Bg vitamers is that of Bain and Williams (1960), 

 who utilized chromatographic separation. The results are summarized in 

 Table 2-36. The extreme fall in brain pyridoxal-P they believe must in some 

 way be related to the convulsions. The rapidity with which the analog can 

 deplete the brain coenzyme is surprising. Is the pyridoxal-P replaced on 

 the apoenzymes by deoxypyridoxol-P ? It seems unlikely that interference 

 with transport or metabolism of pyridoxol could produce such marked ef- 

 fects so soon. Also the displaced pyridoxal-P must be metabolized or leave 

 the tissue. It is not known why pyridoxamine-P does not fall comparably. 

 Dietary vitamin Bg deficiency for 37-51 days does not cause such marked 

 losses of pyridoxal-P or total Bg vitamers from the brain as the single dose 

 of deoxypyridoxol. The severe drop in pyridoxal-P in brain following deoxy- 



