By Leon E. Rosenberg (auth.), Harry Harris, Kurt Hirschhorn (eds.)
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Additional resources for Advances in Human Genetics 6
Chemical structures of the B6 vitamers (pyridoxine, pyridoxal, pyridoxamine) and coenzyme (pyridoxal-5'-phosphate). The coenzyme attaches to its apoenzymes by formation of a Schiff base between the aldehyde group of pyridoxal-5'phosphate and an E-amino nitrogen group of a lysine residue on the apoenzyme. been isolated from foods and extracellular fluid, but none of these is the active coenzyme form. In the cell, these chemically interconvertible precursors are phosphorylated to pyridoxal-5 ' -phosphate (PLP) or pyridoxamine-5' -phosphate by a specific kinase which requires magnesium and ATP.
PLP functions as a coenzyme in such diverse reactions as racemization, transamination, decarboxylation, deamination, alcohol formation, a-f3 elimination, a-f3 addition, and amine oxidation. Snell and his colleagues showed that PLP reacts with amino acids under appropriate conditions to form Schiff bases which promote electron shifts and subsequent metabolic rearrangements. In fact, such Schiff base formation can take place in a protein-free chemically defined system. However, the rate and the Chapter 1: Vitamin-Responsive Metabolic Disorders 41 specificity of such rearrangements have been shown to depend on the interaction between PLP and a specific apoenzyme.
In cystathioninuria, administration of large amounts of pyridoxine leads to marked reduction in urinary excretion of cystathionine, 37 a similar response being observed for excretion of xanthurenic acid and other tryptophan metabolites in patients with xanthurenic aciduria. 159 These in vivo observations were pair~d with interesting data in vitro (Fig. 12). Frimpter36 demonstrated that the liver homogenate from one patient with cystathioninuria had distinctly reduced cystathionase activity and that addition of pyridoxal phosphate to the incubation medium enhanced enzyme activity markedly.
Advances in Human Genetics 6 by Leon E. Rosenberg (auth.), Harry Harris, Kurt Hirschhorn (eds.)