Hyperhomocysteinemia (HHcy) is a term used for the description of a pathological condition associated with high levels of homocysteine (Hcy) in the blood. Studies have suggested S-adenosyl-L-homocysteine (AdoHcy) as a major trigger for deregulated lipid metabolism in HHcy yeast mutant models. AdoHcy is the by-product of S-adenosyl-L-methionine (AdoMet)-dependent methylation reactions and accumulates in HHcy due to the reversal of the S-adenosyl-L-homocysteine hydrolase (Sah1)-catalyzed reaction. It acts as a potent product inhibitor for AdoMet-dependent methylation reactions including the phospholipid (PL) methylation.In this work I provide further evidence for a connection between deregulated lipid metabolism and high AdoHcy levels by investigating HHcy yeast models and comparing them to yeast mutants deficient in PL methylation. Further, an increase of total fatty acids (FA) was shown in both PL methylation deficient yeast and HHcy yeast models. This result indicates an increased de novo FA biosynthesis, which may contribute to TAG accumulation. Gene expression studies in yeast deficient in AdoHcy hydrolysis suggest an impact of AdoHcy accumulation on the expression of genes associated with fatty acid and lipid metabolism. The expression of fatty acyl elongases ELO1 and ELO3 as well as the expression of NTE1, encoding the PC-specific phospholipase B and LRO1, encoding the phospholipid diacylglycerol acyltransferase, were upregulated in AdoHcy accumulating strains. Furthermore, the Opi- phenotype in sah1 mutants is affected by the serine palmitoyltransferase inhibitor myriocin, which suggests an involvement of the sphingolipid metabolism in TAG accumulation. All together, these data suggest that TAG accumulation may be triggered by mechanisms including higher acyltransferase activity, increased de novo FA synthesis, altered PL turnover via Lro1 and up-regulated sphingolipid metabolism.