Methylation Reactions, the Redox Balance and Atherothrombosis: The Search for a Link with Hydrogen Sulfide

 

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Abstract

It is now clear that homocysteine (Hcy) is irreversibly degraded to hydrogen sulfide (H₂S), an endogenous gasotransmitter that causes in vivo platelet activation via upregulation of phospholipase A₂ and downstream boost of the arachidonate cascade. This mechanism involves a transsulfuration pathway. Based on these new data, clinical and experimental models on the relationships between Hcy and folate pathways in vascular disease and information on the Hcy controversy have been reanalyzed in the present review. Most interventional trials focused on Hcy lowering by folate administration did not exclude patients routinely taking the arachidonate inhibitor aspirin. This may have influenced the results of some of these trials. It is also clear that nutritional intake of folate affects several enzymatic reactions of the methionine–Hcy cycle and associated one-carbon metabolism and, thereby, both methylation reactions and redox balance. Hence, it is conceivable that the abnormally high Hcy levels seen in pathologic states reflect a poorly elucidated perturbation of such reactions and of such balance. While it is unknown whether there is an interplay between H₂S, methylation reactions, and redox balance, measuring the sole reduction of blood Hcy that follows folate administration may well be an oversimplified approach to a complex biologic perturbation. The need to investigate this complex framework is thoroughly discussed in this article.

Note

Roberta Lupoli and Alessandro Di Minno equally contributed to the present overview.

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