Abstract
The physiologically active form of vitamin B_6, pyridoxal 5'-phosphate (PLP), is known to function as a cofactor in many enzyme reactions in amino acid metabolism. Recent studies have shown that, apart from its role as a coenzyme, PLP act as a modulator of steroid hormone receptor-mediated gene expression. The induction of cytosolic aspartate aminotransferase (cAspAT) in rat liver by hydrocortisone is suppressed by the administration of pyridoxine. The suppression of the cAspAT induction by pyridoxine is caused by a decrease in the expression of the cAspAT gene, which is brought about by inactivation of the binding activity of the glucocorticoid receptor to the glucocorticoid-responsive element in the regulatory region of the cAspAT gene. Vitamin B_6 has recently been found to modulate gene expression not only for steroid hormone-responsive or PLP-dependent enzymes but also for steroid- and PLP-unrelated protein such as serum albumin. Albumin gene expression was found to be modulated by vitamin B_6 through a novel mechanism that involved inactivation of tissue-specific transcription factors, such as HNF-1 or C/EBP, by direct interaction with PLP in a similar manner to glucocorticoid receptor. We also found that the growth of human hepatoma HepG2 cells was completely inhibited in medium supplemented with pyridoxine in the millimolar range. The anti-tumor effect of vitamin B_6 is not limited to liver cancer alone. Recent studies have shown that dietary supplementation of vitamin B_6 markedly suppresses colon carcinogenesis in mice and mammary tumorigenesis in rats. We further found that antioxidant activity of vitamin B_6 delays homocysteine-induced atherosclerosis in rats. These findings add a new dimension to the hitherto recognized function of vitamin B_6 as a cofactor of enzyme action.
