Regulatory role of cystein dioxygenase in cerebral biosynthesis of taurine. analysis using cerebellum from 3-acetylpyridine-treated rat

Abstract

The effect of 3-acetylpyridine (3-AP) administration on the biosynthesis of taurine in the rat brain has been studied. Treatment with 3-AP induced a significant decrease in the cerebellar contents of taurine and its metabolic precursors, cysteine sulfunic acid (CSA) and cysteic acid (CA), as well as a selective degeneration of climbing fibers i the molecular layer of the cerebellum. It was found that the activity of cerebral cysteine dioxygenase, the enzyme catalyzing the formation of CSA from cysteine, consisted of two systems with low and high K m values. The 3-AP-induced attenuation of cysteine dioxygenase activity with a low m values was noted only in the cerebellum, while that with a high K m value was detected not only in the cerebellum but also in other brain areas such as the medulla oblangata, striatum and cerebral cortex. In contrast, no alteration in the activity of cysteine sulfinic acid decarboxylase (CSD) was observed in any brain areas examined following the administration of 3-AP. Furthermore, it was found that essentially no cystamine as well as a very low activity of cysteamine diocygenase is present in the brain. The present results suggest that taurine in the brain is synthesized from cysteine, mainly by the CSA and CA pathways, and the observed decline of cerebellar taurine in 3-AP-treated rats may be due to an attenuation of the biosynthesis, possibly at the step of cysteine dioxygenase. A possible regulatory role of cysteine dioxygenase with a low K m value in the biosynthesis of cerebral taurine is also suggested.