title: Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology.
abstract: Obesity and diabetes represent a significant and escalating worldwide health burden. These conditions are characterized by abnormal nutrient homeostasis. One such perturbation is altered metabolism of the sulphur-containing amino acid cysteine. Obesity is associated with elevated plasma cysteine, whereas diabetes is associated with reduced cysteine levels. One mechanism by which cysteine may act is through its enzymatic breakdown to produce hydrogen sulphide (H2S), a gasotransmitter that regulates glucose and lipid homeostasis. Here we review evidence from both pharmacological studies and transgenic models suggesting that cysteine and hydrogen sulphide play a role in the metabolic dysregulation underpinning obesity and diabetes. We then outline the growing evidence that regulation of hydrogen sulphide levels through its catabolism can impact metabolic health. By integrating hydrogen sulphide production and breakdown pathways, we re-assess current hypothetical models of cysteine and hydrogen sulphide metabolism, offering new insight into their roles in the pathogenesis of obesity and diabetes.
authors.affiliation: Molecular Metabolism Group, University/BHF Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, UK.
authors.forename: Roderick N
authors.initials: RN
authors.lastname: Carter
authors.affiliation: Molecular Metabolism Group, University/BHF Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, UK.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Morton
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D001786:Blood Glucose; D007328:Insulin; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: adipose, liver; cysteine; diabetes; genetic models; insulin resistance; metabolism; obesity; sulphide