The effect of pyridoxine deficiency on the metabolism of the aromatic amino acids by isolated rat liver cells.
The total activity of three key enzymes and the flux through eight steps of aromatic amino acid metabolism have been determined in liver cells isolated from rats fed either control or pyridoxine-free diet for 5-6 weeks. The pyridoxine-free diet caused a decrease in the catabolism of tyrosine and phenylalanine because of a drop in the flux through tyrosine aminotransferase. This decrease of expressed cellular tyrosine aminotransferase activity can be fully explained in terms of loss of cofactor. Larger decreases in the catabolism of tryptophan were seen after pyridoxine deprivation. The decreased extent of tryptophan catabolism can be solely attributed to loss of cofactor or increased degradation of kynureninase. Inhibition of tryptophan 2,3-dioxygenase was seen in pyridoxine deficiency, probably because of the buildup of the kynurenine metabolites. The control strength of kynureninase, for flux through kynureninase, was calculated to be less than or equal to 0.004, but 0.41 after pyridoxine deprivation. The sensitivity of the three pathways to pyridoxine deprivation is interpreted and discussed in terms of the different affinities for pyridoxal phosphate and the control strengths of the pyridoxal phosphate-dependent enzymes, tyrosine aminotransferase and kynureninase.
D000596:Amino Acids / Q000378:metabolism*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D004044:Dietary Proteins / Q000378:metabolism; D006867:Hydrolases / Q000037:antagonists & inhibitors; D008099:Liver / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D026681:Vitamin B 6 Deficiency / Q000378:metabolism*
D000596:Amino Acids; D004044:Dietary Proteins; D000625:Aminooxyacetic Acid; D014443:Tyrosine; D010649:Phenylalanine; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D006867:Hydrolases; C021480:kynureninase