Ramakrishnan S, Sulochana K N, Lakshmi S, Selvi R, Angayarkanni N
Biochemistry Research Department, Vision Research Foundation, Sankara Nethralaya, Chennai 600 006, India.
Indian J Biochem Biophys. 2006 Oct;43(5):275-83.
The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.
由蛋氨酸形成的氨基酸同型半胱氨酸（Hcy）在健康和疾病方面具有深远意义。在正常情况下，它会在维生素B12和叶酸的帮助下转化为半胱氨酸，并部分重新甲基化为蛋氨酸。然而，当正常代谢受到干扰时，由于胱硫醚-β-合酶缺乏（该酶需要维生素B6来激活），Hcy会在血液中积累，同时蛋氨酸增加，导致智力发育迟缓（I型同型胱氨酸尿症）。半胱氨酸减少可能会由于谷胱甘肽（抗氧化剂）合成减少而导致眼部疾病。在II型、III型和IV型同型胱氨酸尿症中，存在Hcy积累，但蛋氨酸减少，因此不会出现智力发育迟缓。在马凡综合征、一些I型糖尿病病例中发现了高同型半胱氨酸血症，它也与吸烟有关，并且也有遗传基础。在高同型半胱氨酸血症（HHcys）中，临床表现为智力发育迟缓和癫痫发作（仅I型）、晶状体异位、继发性青光眼、视神经萎缩、视网膜脱离、骨骼异常、骨质疏松、血管变化、神经功能障碍和精神症状。还可能会出现血栓形成和心血管疾病。同型半胱氨酸血症的有害影响归因于：（i）Hcy在血液中氧化为同型胱氨酸和二硫化物过程中产生的氧化剂（活性氧物种）。这些氧化剂会氧化膜脂质和蛋白质。（ii）Hcy可以与其巯基与蛋白质反应并形成二硫化物（硫醇化），（iii）它还可以转化为高反应性硫内酯，后者可以与蛋白质反应形成-NH-CO-加合物，从而影响身体的蛋白质和酶。I型同型胱氨酸尿症非常罕见（仅120万分之一），通过补充维生素B6和胱氨酸进行治疗。其他类型更为常见，通过补充叶酸、维生素B12进行治疗，在某些特定情况下，如蛋氨酸合成酶缺乏时，补充蛋氨酸，但要避免过量。在这篇综述中，除了同型半胱氨酸血症有害表现所涉及的分子机制外，还讨论了升高的Hcy水平在心血管、眼部、神经和其他疾病中的作用以及可能的治疗措施。
