562 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



(2) ^ 



Pyridoxol 



4-pyridoxate 



(6) 



(1) 



r 



pyridoxal 



(5) (4) 



(3) 

 (2) 



pyridoxol- P 



(5) 



pyridoxamine ^^ 



(3) 

 (2) , 



pyridoxal -P 



(5)^ 



(4) 



pyridoxamine- P 



(1) pyridoxol oxidase 



(2) pyridoxal kinase 



(3) phosphatase 



(3) 



(4) transaminase 



(5) pyridoxol- P oxidase 



(6) aldehyde oxidase 



Two general types of analog are theoretically possible — those resulting 

 from alteration of the pyridine ring and those in which the substituent 

 groups are modified, replaced, or eliminated — but practically it has been 

 found thus far that only analogs of the second type are effective. Actually, 

 not many really effective analogs have been found. The most commonly 

 used analog has been deoxypyridoxol* and we shall limit our discussion 

 mainly to this substance. Unless otherwise noted, the name deoxypyridoxol 

 will refer only to the 4-derivative. 



Deoxypyridoxol was found to have no vitamin Bg activity by Unna (1940) 

 and to be an antagonist of pyridoxine in the chick by Ott (1946). Chicks 

 on a low pyridoxine diet can be killed by as little as 16 //g deoxypyridoxol, 

 whereas normal chicks on an adequate pyridoxine diet can withstand as 

 much as 600 //g. By varying the relative doses of both vitamin and analog, 

 Ott showed that approximately 2 molecules of analog can counteract 1 

 molecule of pyridoxine. Deoxypyridoxol has since been found to inhibit cer- 

 tain microorganisms and to produce symptoms of vitamin Bg deficiency in 

 animals, including man. 4-Methoxymethylpyridoxol (usually called methox- 

 ypyridoxine) was found by Unna to have slight vitamin activity in the 

 rat, but Ott (1947) demonstrated a potent inhibitory effect in the chick. 

 The ability of rats to use this analog is related to its transformation to 

 pyridoxal in these animals (Porter et al., 1947). In the chick it is about 25 

 times as effective as deoxypyridoxol. These are apparently the only analogs 

 so far tested that can produce rather typical pyridoxine-deficiency symp- 

 toms in animals, although several others can inhibit microbial growth by 

 disturbing pyridoxal function. Toxopyrimidine is undoubtedly toxic to ani- 

 mals and can be antagonized by pyridoxine, but it is debatable whether 



* This is 4-deoxypyridoxol and has previously been called desoxypjTidoxine or 

 deoxypyridoxine. However, if we are to conform to the modern nomenclature, the 

 specific compound must be deoxypyridoxol. Deoxypyridoxine might be used to refer 

 to the entire group of deoxy substances exhibiting vitamin Bg activity antagonism. 



