ArticleThe Journal of biological chemistry2008
S-adenosyl-L-homocysteine hydrolase, key enzyme of methylation metabolism, regulates phosphatidylcholine synthesis and triacylglycerol homeostasis in yeast: implications for homocysteine as a risk factor of atherosclerosis.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
- Homocysteine and S-adenosyl-L-homocysteine impair development and methylation in yeast and flies.Disease models & mechanisms · 2026Article
- Bacterial cell fate under stress: lipid remodeling and antimicrobial peptide attack.npj antimicrobials and resistance · 2026Article
- Evidence for a hydrogen sulfide-sensing E3 ligase in yeast.Genetics · 2024Article
- Structure and Catalytic Mechanism of Radical SAM Methylases.Life (Basel, Switzerland) · 2022Review
- Identification of novel inhibitors of S-adenosyl-L-homocysteine hydrolase via structure-based virtual screening and molecular dynamics simulations.Journal of molecular modeling · 2022Article
- Predicting target-ligand interactions with graph convolutional networks for interpretable pharmaceutical discovery.Scientific reports · 2022Article
- S-adenosyl-L-homocysteine hydrolase FgSah1 is required for fungal development and virulence inVirulence · 2021Article
- Lipid remodeling in response to methionine stress in MDA-MBA-468 triple-negative breast cancer cells.Journal of lipid research · 2021Article
- Responses of a Newly Evolved Auxotroph of Chlamydomonas to BPlant physiology · 2020Article
- Metabolic Peculiarities ofFrontiers in microbiology · 2019Article
- Attenuation of utero-toxicity, metabolic dysfunction and inflammation by soy protein concentrate in rats exposed to fluoridated water: consequence of hyperlipidemia in parallel with hypohomocysteinemia.Environmental science and pollution research international · 2018Article
- NMT1 and NMT3Plant physiology · 2018Article
- Homocysteine regulates fatty acid and lipid metabolism in yeast.The Journal of biological chemistry · 2018Article
- Carnitine Requires Choline to Exert Physiological Effects inFrontiers in microbiology · 2018Article
- A Metabolic Function for Phospholipid and Histone Methylation.Molecular cell · 2017Article
- Identification and functional characterization of the sulfate transporter gene GmSULTR1;2b in soybean.BMC genomics · 2016Article
- Regulation of S-adenosylhomocysteine hydrolase by lysine acetylation.The Journal of biological chemistry · 2014Article
- Arabidopsis lipins, PDAT1 acyltransferase, and SDP1 triacylglycerol lipase synergistically direct fatty acids toward β-oxidation, thereby maintaining membrane lipid homeostasis.The Plant cell · 2014Article
- The response to inositol: regulation of glycerolipid metabolism and stress response signaling in yeast.Chemistry and physics of lipids · 2014Review
- The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as transcription factor-specific mitochondrial and other cell activities.BMC genomics · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In eukaryotes, S-adenosyl-L-homocysteine hydrolase (Sah1) offers a single way for degradation of S-adenosyl-L-homocysteine, a product and potent competitive inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases. De novo phosphatidylcholine (PC) synthesis requires three AdoMet-dependent methylation steps. Here we show that down-regulation of SAH1 expression in yeast leads to accumulation of S-adenosyl-L-homocysteine and decreased de novo PC synthesis in vivo. This decrease is accompanied by an increase in triacylglycerol (TG) levels, demonstrating that Sah1-regulated methylation has a major impact on cellular lipid homeostasis. TG accumulation is also observed in cho2 and opi3 mutants defective in methylation of phosphatidylethanolamine to PC, confirming that PC de novo synthesis and TG synthesis are metabolically coupled through the efficiency of the phospholipid methylation reaction. Indeed, because both types of lipids share phosphatidic acid as a precursor, we find in cells with down-regulated Sah1 activity major alterations in the expression of the INO1 gene as well as in the localization of Opi1, a negative regulatory factor of phospholipid synthesis, which binds and is retained in the endoplasmic reticulum membrane by phosphatidic acid in conjunction with VAMP/synaptobrevin-associated protein, Scs2. The addition of homocysteine, by the reversal of the Sah1-catalyzed reaction, also leads to TG accumulation in yeast, providing an attractive model for the role of homocysteine as a risk factor of atherosclerosis in humans.
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