title: S-adenosyl-L-homocysteine hydrolase and methylation disorders: yeast as a model system.
abstract: S-adenosyl-L-methionine (AdoMet)-dependent methylation is central to the regulation of many biological processes: more than 50 AdoMet-dependent methyltransferases methylate a broad spectrum of cellular compounds including nucleic acids, proteins and lipids. Common to all AdoMet-dependent methyltransferase reactions is the release of the strong product inhibitor S-adenosyl-L-homocysteine (AdoHcy), as a by-product of the reaction. S-adenosyl-L-homocysteine hydrolase is the only eukaryotic enzyme capable of reversible AdoHcy hydrolysis to adenosine and homocysteine and, thus, relief from AdoHcy inhibition. Impaired S-adenosyl-L-homocysteine hydrolase activity in humans results in AdoHcy accumulation and severe pathological consequences. Hyperhomocysteinemia, which is characterized by elevated levels of homocysteine in blood, also exhibits a similar phenotype of AdoHcy accumulation due to the reversal of the direction of the S-adenosyl-L-homocysteine hydrolase reaction. Inhibition of S-adenosyl-L-homocysteine hydrolase is also linked to antiviral effects. In this review the advantages of yeast as an experimental system to understand pathologies associated with AdoHcy accumulation will be discussed.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria. oksana.tehlivets@uni-graz.at
authors.forename: Oksana
authors.initials: O
authors.lastname: Tehlivets
authors.forename: Nermina
authors.initials: N
authors.lastname: Malanovic
authors.forename: Myriam
authors.initials: M
authors.lastname: Visram
authors.forename: Tea
authors.initials: T
authors.lastname: Pavkov-Keller
authors.forename: Walter
authors.initials: W
authors.lastname: Keller
mesh_terms: D043383:Adenosylhomocysteinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D012436:S-Adenosylmethionine; D043383:Adenosylhomocysteinase