Metabolic Imbalance of Homocysteine and Hydrogen Sulfide in Kidney Disease

Title:Metabolic Imbalance of Homocysteine and Hydrogen Sulfide in Kidney Disease

Volume: 25 Issue: 3

Author(s): Karmin O*Yaw L. Siow

Affiliation:

• Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg,Canada

Keywords: Homocysteine, hydrogen sulfide, sulfur-containing amino acid, ischemia-reperfusion, transsulfuration pathway, oxidative stress.

Abstract: 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.

Cite this article as:

O Karmin*, Siow L. Yaw , Metabolic Imbalance of Homocysteine and Hydrogen Sulfide in Kidney Disease, Current Medicinal Chemistry 2018; 25 (3) . https://dx.doi.org/10.2174/0929867324666170509145240