Siow Yaw L
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
Department of Animal Science, University of Manitoba, Winnipeg, Canada.
Curr Med Chem. 2018 Jan 30;25(3):367-377. doi: 10.2174/0929867324666170509145240.
Homocysteine (Hcy) and hydrogen sulfide (H2S) are important molecules produced during the metabolism of sulfur-containing amino acids. Hcy metabolism is central to the supply of methyl groups that are essential for biological function. Hcy can be either regenerated to methionine or metabolized to cysteine, a precursor for glutathione synthesis. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) play a crucial role in metabolizing Hcy to cysteine through the transsulfuration pathway. These two enzymes are also responsible for H2S generation through desulfuration reactions. H2S, at physiological levels serves as a gaseous mediator and has multifaceted effects. Metabolic imbalance of Hcy and H2S has been implicated in pathological conditions including oxidative stress, inflammation, cardiovascular and cerebral dysfunction, fatty liver disease and ischemiareperfusion injury. Organs such as liver, kidney, gut and pancreas contain all the enzymes that are required for Hcy metabolism. The kidney plays an important role in removing Hcy from the circulation. Hyperhomocysteinemia, a condition of elevated blood Hcy level, is a common clinical finding in patients with chronic kidney disease (CKD) or acute kidney injury (AKI), the latter is often caused by ischemia-reperfusion. This paper reviews exiting literatures regarding (1) the role of kidney in regulating Hcy and H2S metabolism; (2) disruption of sulfur-containing amino acid metabolism during ischemiareperfusion; (3) impact of metabolic imbalance of Hcy and H2S on kidney function. Better understanding of molecular mechanisms that regulate Hcy and H2S metabolism under physiological and pathophysiological conditions will help improve therapeutic strategies for patients with kidney disease or other organ injuries.
同型半胱氨酸（Hcy）和硫化氢（H₂S）是含硫氨基酸代谢过程中产生的重要分子。Hcy代谢对于提供生物功能所必需的甲基至关重要。Hcy既可以再生为甲硫氨酸，也可以代谢为半胱氨酸，后者是谷胱甘肽合成的前体。胱硫醚-β-合酶（CBS）和胱硫醚-γ-裂解酶（CSE）在通过转硫途径将Hcy代谢为半胱氨酸的过程中起关键作用。这两种酶还通过脱硫反应负责生成H₂S。生理水平的H₂S作为一种气体介质，具有多方面的作用。Hcy和H₂S的代谢失衡与包括氧化应激、炎症、心血管和脑功能障碍、脂肪肝疾病以及缺血再灌注损伤在内的病理状况有关。肝脏、肾脏、肠道和胰腺等器官含有Hcy代谢所需的所有酶。肾脏在从循环中清除Hcy方面起重要作用。高同型半胱氨酸血症，即血液中Hcy水平升高的情况，是慢性肾脏病（CKD）或急性肾损伤（AKI）患者常见的临床发现，后者通常由缺血再灌注引起。本文综述了现有文献，内容涉及：（1）肾脏在调节Hcy和H₂S代谢中的作用；（2）缺血再灌注期间含硫氨基酸代谢的紊乱；（3）Hcy和H₂S代谢失衡对肾功能的影响。更好地理解生理和病理生理条件下调节Hcy和H₂S代谢的分子机制，将有助于改善肾病或其他器官损伤患者的治疗策略。
