ANALOGS OF PYRIDOXAL 561 



most potently inhibited. With regard to the inhibition of growth, it might 

 be well to consider more carefully the changes resulting from complexes 

 formed between quinacrine and nucleotides or nucleic acids. 



ANALOGS OF PYRIDOXAL 



A group of substances, including pyridoxol, pjTidoxal, pyridoxamine, and 

 their phosphates, possess vitamin Bg activity and these will be designated 

 as pyridoxine in accordance with Braunstein (1960) and the Commission 

 on Chemical Terminology of the International Union of Pure and Applied 

 Chemistry (the substance previously called pyridoxine now being pyridoxol). 

 These substances are converted to pyridoxal which is metabolically func- 

 tional in the form of its phosphate. Pyridoxal-P is the coenzyme for a large 

 number of enzymes involved in the decarboxylation, transamination, oxi- 

 dative deamination, racemization, a,/?-cleavage, and /?- and y-substituent 

 replacement in amino acid metabolism, and, in addition, may be active in 

 amino acid transport. Disturbances in pyridoxal metabolism or functions 

 will thus bring about primarily alterations in the biosynthesis and degra- 

 dation of amino acids, and indirectly will affect protein synthesis and a 

 variety of other metabolic pathways. Possibly the most important biochem- 

 ical defect will be the reduction in transaminations involving glutamate, 

 inasmuch as these reactions are central in amino acid metabolism. More 

 recently it has been found that phosphorylase a contains pyridoxal-P, per- 

 haps bound in an aldamine linkage, and, although initially it was believed 

 that it is enzymically nonfuctional, the demonstration by Illingworth et al. 

 (1958) that pyridoxal and 5-deoxy pyridoxal will prevent the binding of 

 pyridoxal-P and enzyme activity points to some role of the pyridoxal-P 

 in the catalysis. 



Animals generally require pyridoxine whereas plants and most micro- 

 organisms can synthesize pyridoxal. Little is known about the biosynthesis 

 of pyridoxal, but the rather complex interrelationships between the pyri- 

 doxines and their phosphates are now fairly clear. The pathways and the 

 enzymes involved are summarized in the accompanying diagram (Braun- 

 stein, 1960; Wada and Snell, 1961). It is believed that the major pathway 

 for the formation of pyridoxal-P is 



Pyridoxol -^ pyridoxol-P -> pyridoxal-P 



The primary excretory metabolite of pyridoxal is 4-pyridoxate and its lac- 

 tone. Most of the pyridoxine in tissues is present as pyridoxal-P bound quite 

 tightly to enzymes and other proteins. Certain analogs can inhibit the for- 

 mation of pyridoxal-P and may act partly in this way, while other analogs 

 may be phosphorylated and compete with pyridoxal-P. 



