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.
