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STUDIES ON THE METABOLIC DETERMINANTS OF D‐GALACTOSE‐INDUCED NEUROTOXICITY IN THE CHICK 1

1971; Wiley; Volume: 18; Issue: 11 Linguagem: Inglês

10.1111/j.1471-4159.1971.tb05080.x

1471-4159

Leslie P. Kozak, William W. Wells,

Polyamine Metabolism and Applications

Abstract The contents of galactose, galactitol, galactose 1‐phosphate, UDP‐galactose and UDP‐glucose in the brains of chicks fed a diet containing 40 % (w/w) D‐galactose were determined at regular intervals during a 48 h period which terminated in convulsive activity and death of the animals. Although levels of galactose and galactitol were markedly elevated, UDP‐galactose and UDP‐glucose levels were not significantly increased. The level of galactose 1‐phosphate rose to 1‐3 μg/g of fresh tissue by 14 h but gradually diminished until, at 48 h, the content was 0‐25 μg/g. The metabolic turnover of these compounds, as shown by labelling experiments with inorganic [ 32 P]phosphate and [U‐ 14 C]galactose, indicated that galactose 1‐phosphate and UDP‐galactose were rapidly metabolized, yet relatively little galactose was utilized by the brain as a source of energy. These observations have prompted us to propose a mechanism for the turnover of galactose 1‐phosphate that involves cyclical phosphorylation and dephosphorylation reactions in the brains of galactose‐fed chicks. In support of this hypothesis, we have identified phosphatase activity which has a relatively low K m value for galactose 1‐phosphate (0‐06‐0‐07 mM) in virtually all subcellular fractions of homogenates of chick brain. Maximum activity of the phosphatase is several‐fold greater than that recorded for galactokinase (EC 2.7.1.6) and galactose 1‐phosphate uridyltransferase (EC 2.7.710) from chicken brain.