Some Effects of ω-Methyl Analogues of Vitamin B 6 in Rats

Abstract

Summary

ω-Methylpyridoxal, ω-methylpyridoxamine and ω-methylpyridoxine support growth of rats for several weeks following deletion of vit. B₆ from the ration. Eventually, however, growth rate in the presence of these compounds slows, and becomes equal to or less than that of vit. B₆-deficient control animals. The period of growth promotion is decreased greatly when the compounds are administered to depleted rats. Following this period of growth-promotion, growth with high concentrations of ω-methylpyridoxine is distinctly less than that in control animals; and death results well before any deaths are noted in the control group. In uncomplicated vit. B₆ deficiency on this ration convulsive seizures are infrequent and were observed only following approximately 6 weeks on the deficient diet. In contrast, in the animals fed the ω-methyl analogues of vit. B₆ convulsions occurred frequently, in all animals, starting about 2 weeks after supplementation while substantial weight gains were still occurring. All of these symptoms were prevented by feeding pyridoxal together with the analogues. Following administration of ω-methylpyridoxine to animals, ω-methyl-4-pyridoxic acid appears in the urine in amounts similar to those found for 4-pyridoxic acid following pyridoxine administration. Glutamic-aspartic transaminases and thionase are reduced in ω-methylpyridoxine-fed animals to about the levels found during uncomplicated vit. B₆ deficiency. Correspondingly, ω-methylpyridoxal phosphate was only about 11% as active as pyridoxal phosphate in activating the glutamic-aspartic transaminase, and did not fully activate liver thionase at any concentration. The facts that feeding thes analogues first promotes, but eventually inhibits growth, and produces a deficiency of a different type than that found in uncomplicated vit. B₆-deficiency, may be interpreted in terms of (a) the dual character of ω-methylpyridoxal phosphate as an activator for some vit. B₆-dependent enzymes, but not for others, (b) its role as a strutural antagonist for vit. B₆ in those enzymes that it does not activate, and (c) the role of these analogues as competitive substrates for vit. B₆ in reactions leading to destruction of the vitamin.