SECTION OF BIOLOGY: Studies on the Pathologic Effects Produced by Two Analogues of Pyridoxine*

Abstract

Analogues of Pyridoxine." (This lecture was illustrated by lantern slides.)Although inhibitors and poisons have been used for a long time in the study of isolated enzyme systems, it has been only in relatively recent years that physiological studies have been made with specific metabolite antagonists. Compounds with chemical structures similar to vitamins, hormones, and amino acids have been prepared which antagonize or inhibit such metabolites.' The term, antivitamin, has been applied to those compounds which counteract the function of vitamins. The inhibition ratio, or the ratio of antivitamin to vitamin that must be present for efficacy, is quite high for most antivitamins. Thus, in the case of pyrithiamine,* a thiamine antagonist, a ratio of approximately 40:l exists; that is, 40 moles of antivitamin are required to counteract the effect of 1 mole of the vitamin. Ott3 has recently reported that 2,4-dimethyl-3-hydroxy-5-hydroxymethylpyridine (desoxypyridoxine) possesses potent antipyridoxine activity in the chick. This compound has an inhibition ratio of 2:l and may therefore be considered the most potent of the vitamin B inhibitors yet discovered. Ott has also demonstrated4 that 2-methyl-3-hydroxy-4-methoxymethyl-5-hydroxymethylpyridine (methoxypyridoxine) is almost as potent an inhibitor of pyridoxine in chicks as is desoxypyridoxine. Methoxypyridoxine has been shown to possess pyridoxine activity in the rat, but no such activity has been observed with deso~ypyridoxine.~ Biochemical studies conducted by Porter, Clark, and Silbere reveal that pyridoxine-deficient rats treated with desoxypyridoxine and tryptophane excrete increased quantities of xanthurenic acid and kynurenine. Under comparable conditions, methoxypyridoxine effects a decreased excretion of these metabolic products.I n order to evaluate further the antipyridoxine activity of desoxy-This paper was presented by Doctor Mushett.

Pyridoxine Deficiency in Human Beings Induced With Desoxypyridoxine 1

“…Ott (28) reported on the antipyridoxine activity of one of these antimetabolites, desoxypyridoxine, and found the inhibitory ratio to be 2: 1 in chicks. Mushett, Stebbins and Barton (29) have reported a study of pathologic changes resulting from growth reversal by this compound and found that these changes were similar to those found in pyridoxine deficient animals, the chick, puppies, and monkeys. Stoerk (30) reported that lymphosarcoma transplants failed to grow in mice on a pyridoxine deficient diet and that these implants regressed when mice were placed on a deficient diet and desoxypyridoxine was added to the regimen.…”

The Effect of Diet on the Susceptibility of the Mouse to Pneumonia Virus of Mice (Pvm)

“…Effect of DesoxypyridoxineS.--Since desoxypyridoxine has been found to be a powerful inhibitor of the biological activity of pyridoxine in chicks (35,36), dogs and monkeys (35), and rats (38), it seemed possible that this vitamin analogue might have some influence on the susceptibility of mice to infections with PVM. In a preliminary experiment weanling mice after inoculation with PVM were fed a diet containing no pyridoxine (S-3) and were given desoxypyridoxine 2.0 mg. per 100 cc.…”

Metabolic Inhibitors

“…so Desoxypyridoxine given to tryptophane-fed, pyridoxine-deficient rats caused an increased excretion of xanthurenic acid (121). The histological changes in tissues of chicks, monkeys, and dogs induced by desoxypyridoxine include an anemia and atrophy of spleen, lymph nodes, thymus gland, and the blood forming con- stituents of the bone marrow (122). Antibody responses were impaired and a marked atrophy of lymphoid tissue in rats and mice resulted from the administration of desoxypyri' doxine (123).…”