Sulfhydryl groups as targets of mercury toxicity Original paper

What was reviewed?

This review examined how mercury causes toxicity by binding to sulfhydryl (thiol, –SH) groups in biological molecules. The authors focused on how mercury’s strong attraction to cysteine residues and other thiol-containing ligands shapes mercury’s chemical forms in the body, its transport between tissues, and the downstream cellular pathways that lead to organ injury.

Who was reviewed?

The authors reviewed evidence from experimental and mechanistic research rather than a single patient cohort. They integrated findings from biochemical studies, animal and cell models, and proteomic work that mapped mercury-reactive cysteines across many proteins, then used that evidence to explain how thiol targeting links exposure to neurologic, renal, hepatic, and cardiovascular effects.

What were the most important findings?

The review emphasized that cysteine is mercury’s primary target, and that glutathione is a major competing thiol that both binds mercury and influences toxicity by controlling antioxidant capacity. In blood, albumin acts as a dominant mercury-binding protein through its free cysteine site, but mercury can rapidly exchange among available thiols, which enables redistribution into tissues. Mercury–thiol binding can directly inactivate enzymes and structural proteins through S-mercuration, disrupt mitochondrial function, and drive oxidative stress by limiting glutathione and thioredoxin availability and by impairing key antioxidant enzymes such as Mn-SOD and thioredoxin reductase.

What are the greatest implications of this review?

Clinically, the review supports a thiol-centered model of mercury harm: symptom risk depends not only on exposure dose but also on ligand availability, redox reserve, and tissue-specific vulnerability of thiol-dependent proteins. This framework helps explain why patients can show different organ patterns at similar measured mercury levels and why oxidative stress and sulfur metabolism markers may add context when evaluating exposure-related complaints. The review also strengthens the rationale for supportive strategies that protect thiol pools and antioxidant systems alongside exposure reduction, while acknowledging that many true thiol-mediated targets remain unmapped and that mercury effects can also occur through mechanisms not fully explained by thiol binding alone.