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S-adenosyl-L-homocysteine hydrolase and methylation disorders: Yeast as a model system
- Source :
- Biochimica et Biophysica Acta
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.<br />Highlights ► AdoHcy is a potent product inhibitor of AdoMet-dependent methyltransferases. ► AdoHcy accumulates in hyperhomocysteinemia. ► Yeast is an advantageous system to understand AdoHcy toxicity. ► Lipid metabolism is deregulated in response to AdoHcy accumulation.
- Subjects :
- S-Adenosylmethionine
Hyperhomocysteinemia
Saccharomyces cerevisiae Proteins
Methyltransferase
Homocysteine
S-adenosyl-L-homocysteine hydrolase
Review
Saccharomyces cerevisiae
Biology
AdoHcy
Methylation
Models, Biological
AdoMet
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Hydrolase
medicine
Animals
Humans
heterocyclic compounds
Molecular Biology
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Adenosylhomocysteinase
medicine.disease
Molecular biology
Enzyme
chemistry
Biochemistry
030220 oncology & carcinogenesis
Molecular Medicine
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1832
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Accession number :
- edsair.doi.dedup.....4e1688663bbe0512c6405f77d55c394f
- Full Text :
- https://doi.org/10.1016/j.bbadis.2012.09.007