Pathways and regulation of homocysteine metabolism in mammals
Pathways and regulation of homocysteine metabolism in mammals
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DOI：
10.1055/s-2000-8466
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发表时间：
2000-01-01
影响因子：
5.7
通讯作者：
Finkelstein, JD
中科院分区：
文献类型：
--
作者：
Finkelstein, JD
甲硫氨酸循环和转硫序列这两个交叉的途径构成了哺乳动物高半胱氨酸代谢的机制。甲硫氨酸循环发生在所有组织中，并提供同型半胱氨酸的再甲基化，从而保存甲硫氨酸。此外，该循环对于甲基四氢叶酸的再循环至关重要。硫胱苷肽的合成是同型半胱氨酸催化转化为半胱氨酸和硫酸盐的不可逆途径中的第一个反应。该途径分布有限，主要存在于肝脏、肾脏、小肠和胰腺中。同型半胱氨酸代谢的调节是通过改变分布在两个竞争途径之间的同型半胱氨酸的量来实现的。有两种机制是管理过程的基本机制。相关酶的组织含量的变化是对持续扰动的反应。酶的固有动力学特性提供了对底物和其他代谢效应物的组织浓度变化的立即响应。S-腺苷甲硫氨酸、S-腺苷高半胱氨酸和甲基四氢叶酸在这方面特别重要。
Two intersecting pathways, the methionine cycle and the transsulfuration sequence, compose the mechanisms for homocysteine metabolism in mammals. The methionine cycle occurs in all tissues and provides for the remethylation of homocysteine, which conserves methionine. In addition, the cycle is essential for the recycling of methyltetrahydrofolate. The synthesis of cystathionine is the first reaction in the irreversible pathway for the catabolism of homocysteine by means of the sequential conversion to cysteine and sulfate. This pathway has a limited distribution and is found primarily in the liver, kidney, small intestine and pancreas. Regulation of homocysteine metabolism is achieved by changes in the quantity of homocysteine distributed between the two competing pathways. Two mechanisms are basic to the regulatory process. Changes in tissue content of the relevant enzymes are the response to sustained perturbations. The inherent kinetic properties of the enzymes provide an immediate response to alterations in the tissue concentrations of substrates and other metabolic effecters. S-adenosylmethionine, S-adenosylhomocysteine, and methyltetrahydrofolate are of particular importance in that context.