The Physiological Role of Flavin-dependent Oxidases in Mammalian Peroxisome

巯基化合物和乙醛酸的加合物是过氧化物酶体中黄素氧化酶的底物。产物可水解为草酰硫酯，草酰硫酯被认为是代谢效应物。另一方面，某些酶和受体的活性可以通过硫醇/二硫键交换反应来调节。噻唑烷-2-羧酸盐（Thiazolidine-2-carboxylic acid，TC）是半胱胺和乙醛酸的加合物，是D-氨基酸氧化酶（D-amino acid oxidase，DAO）的底物。TC氧化酶活性在大鼠各组织中的组织化学定位与DAO的定位雅阁。这两种氧化酶活性的组织化学和生物化学显示，是由于相同的酶，DAO。DAO的活性仅定位于下脑干、小脑和脊髓，并且仅存在于星形胶质细胞和Bergmann胶质细胞中，而不存在于其他类型的胶质细胞、神经元、内皮细胞或室管膜细胞中。DAO活性在各种突触周围的胶质间隙中所占比例较大，而D-天冬氨酸氧化酶活性在未检测到DAO活性的终脑中发现，表明这两种氧化酶在脑中的分布是互补的。另一方面，还研究了巯基化合物如半胱胺对血管平滑肌和膜结合磷脂酶A_2的直接作用。从这些结果，过氧化物酶体黄氧化酶的可能性是参与细胞的调节，通过参与巯基化合物的代谢和草酰硫醇酯的生物合成。

Adducts of sulfhydryl compounds and glyoxylate are substrates for the flavooxidases in peroxisome. The products can be hydrolyzed to oxalyl thiol ester which is proposed to be a metabolic effector. On the other hand, the activities of certain enzymes and receptors can be modulated by thiol/disulfide exchange reactions. The intracellular thiol/disulfide status appears to play an important role in cellular regulations and responses.Thiazolidine-2-carboxylate (TC), an adduct of cysteamine and glyoxylate, is a substrate for D-amino acid oxidase (DAO). The histochemical localizations of TC oxidase activity in various tissues of rat were in accord with those of DAO. Both oxidase activities were histochemically and biochemically shown to be due to the same enzyme, DAO. The activity of DAO was localized exclusively in the lower brain stem, cerebellum and spinal cord, and to be present only in astrocytes and Bergmann glial cells, but not in other types of glial cells, neurons, endothelial cells or ependymal cells. The greater proportion of DAO activity was present in the glial spaces around various kinds of synapses, whereas D-aspartate oxidase activity was found in the endbrain in which DAO activity was not detectable, suggesting that the distribution of the two oxidases is supplementary in brain. On the other hand, the direct actions of sulfhydryl compounds such as cysteamine to vascular smooth muscle and membrane-bound phospholipase A_2 were also investigated. From these results, the possibility is suggested that peroxisomal flavooxidases are involved in the cellular regulations by participating in metabolisms of sulfhydryl compounds and biosynthesis of oxalyl thiol ester.