Stability of some Pyridoxal Phosphate-dependent Enzymes in Vitamin B-6 Deficient Rats

Abstract

The effects of lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme.

Regulation of GABA Metabolism in Discrete Rabbit Brain Regions under Methoxypyridoxine—Regional Differences in Cofactor Saturation and the Preictal Activation of Glutamate Decarboxylase Activity1

“…In fact, it has been proposed that the extent to which a B6dependent enzyme is inhibited by an antimetabolite is a function of the relative affinities of the apoenzymes toward the coenzyme (Snell, 1958) and that, therefore, in an in vivo experiment, antimetabolites do not necessarily inhibit all B,-dependent enzymes to the same degree, but particularly those whose coenzyme will easily dissociate from the apoenzyme (Holtz and Palm, 1964). To interpret this in different terms, the differences in the proportions of enzymes existing as holo-and apoenzyme determine the extent of inhibition (Hunter and Harper, 1976). These findings of B, enzymes catalyzing different reactions obviously also hold for the same enzyme with regionally different properties.…”

Effect of ethanol on polyamine synthesis during liver regeneration in rats.

“…Because chronic ethanol consumption reduces plasma and tissue concentrations of PLP (46), a factor necessary for ODC activity (47), it is tempting to speculate that posttranslational inhibition of ODC activity is due to PLP deficiency. However, while PLP deficiency may contribute to ethanol-associated inhibition of polyamine synthesis in vivo, it cannot explain the inhibition of ODC activity noted in the present study.…”

Recent advances in the mechanism of pyridoxine‐responsive disorders

“…Taken together these findings suggest that PLP may stabilise mutant CS molecules possibly by influencing the proportions of apo-and holo-CS in vivo, in a similar manner to that observed for other PLP enzymes. For example, tyrosine aminotransferase (EC 2.6.1.5) in the liver of rats (Snape et al, 1980), serine dehydratase (EC 4.2.1.13) in vitamin B6-deficient rats (Hunter and Harper, 1976), aspartate aminotransferase (EC 2.6.1.1) in rat tissues (Okada and Hirose, 1979) and, finally, partially purified cystathionase which was protected by PLP against degradation by proteolytic enzymes (Chatagner et al, 1970). Recently, Skovby et al (1984) have reported studies of biogenesis ofCS subunits which suggest that there can be a normal rate of synthesis of mutant CS molecules whose stability is much reduced.…”