VITAMIN B 6 MODULATION OF GENE EXPRESSION

Abstract

Physiologically active form of vitamin B 6, pyridoxal 5′-phosphate (PLP), is known to function as a cofactor in many enzyme reactions of amino acid metabolism. Recent studies have shown that, apart from its role as a coenzyme, PLP acts as a modulator of steroid hormone receptor-mediated gene expression. Specifically, elevation of intracellular PLP levels leads to decreased transcriptional responses to glucocorticoid, progesterone, androgen, or estrogen hormones. For instance, the induction of aspartate aminotransferase (cAspAT) in rat liver by hydrocortisone is suppressed by the administration of pyridoxine. The suppression of cAspAT induction by pyridoxine is caused by a decrease in the expression of cAspAT gene which is brought about by inactivation of the binding activity of glucocorticoid receptor to glucocorticoid-responsive element in the regulatory region of cAspAT gene. Vitamin B 6 has recently been found to modulate gene expression for not only steroid hormone-responsive or PLP-dependent enzymes but also for steroid hormone/PLP-unrelated proteins such as serum albumin. Albumin gene expression was found to be modulated by vitamin B 6 through a novel mechanism that involves 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. Enhancement of albumin gene expression in the liver by an increased supply of amino acids can be explained by elevated binding activities of HNF-1 and C/EBP to respective DNA-binding site which, in turn, are caused by a decrease in the intracellular level of PLP by the amino acid supply. These findings---that vitamin B 6 acts as a physiological modulator of gene expression---add a new dimension to the hitherto-recognized function of vitamin B 6 as a cofactor of enzyme action. © 1997 Elsevier Science Inc.