574 2. ANALOGS OF ENZYME REACTION COMPONENTS 



butyrate content of the brain increases (Purpura et al., 1960). These dis- 

 crepancies might be removed if one could determine local changes in y-ami- 

 nobutyrate in the central nervous system. On the other hand, it is possible 

 that other disturbances are more pertinent to the convulsive state, and, as 

 Rosen et al. (1960) have pointed out, perhaps more thought should be given 

 to the interference with the transport of amino acids into the brain cells. 

 Variations in the metabolism of amino acids other than glutamate and the 

 levels of physiologically active amines have not been studied. In this con- 

 nection it is interesting that Schrodt et al. (1960) administered deoxypyri- 

 doxol to two patients with malignant carcinoid syndrome at doses of 100- 

 200 mg/day, and found in one patient a fall in the urinary excretion of 5- 

 hydroxyindoleacetate, which is the primary product of serotonin metab- 

 olism, along with symptoms of vitamin Bg deficiency. 



The role of pyridoxal in lipid metabolism is not yet clear but there is 

 some evidence in animals for a requirement in fatty acid synthesis. When 

 deoxypyridoxol was administered to seven subjects at 300 mg/day, six de- 

 veloped symptoms of pyridoxine deficiency (Mueller et al., 1959). There was 

 a general decrease in the polyunsaturated fatty acids of the blood, but no 

 change is phospholipids or cholesterol. This was believed to be evidence 

 for the involvement of pyridoxine in maintaining blood fatty acids through 

 participation in the synthetic reactions, but the data do not indicate a role 

 in the interconversion of the unsaturated fatty acids. 



Effects on Active Transport 



Although relatively Httle has been done with respect to the actions of 

 pyridoxine analogs, there is accumulating evidence that amino acid trans- 

 port is often related to pyridoxal-P function, and it is likely that some of 

 the toxic effects of the analogs will be explained on this basis. Part of the 

 transport of amino acids across the intestinal wall is active and is inhibited 

 by deoxypyridoxol (Fridhandler and Quastel, 1955). A 41% inhibition of 

 L-alanine transport was observed with 10 mM deoxypyridoxol, which is 

 certainly a very high concentration; however, pyridoxol at the same con- 

 centration has no effect. The inhibition is not antagonized by pyridoxol, 

 pyridoxal, or pyridoxal-P, which may indicate that phosphorylation is not 

 rapid enough intracellularly and that the coenzyme itself cannot penetrate, 

 or that the inhibition is not an antagonism of pyridoxine. A rather disturb- 

 ing fact is that glucose and fructose transport is also inhibited by deoxy- 

 pyridoxol to about the same extent as alanine absorption, so that this is 

 not a specific effect on amino acid transport. 



The transport of d- and L-methionine across rat intestine is depressed 

 by deoxypyridoxol injected at 200-400 //g/day (Jacobs, 1958; Jacobs and 

 Hillman, 1958). The effect appears within an hour after intraperitoneal 

 injection and can be abolished by injection of pyridoxol (see accompanying 



