Biotinidase Activity Inhibition as a Biomarker of Effect to Mercury: Evidence from Amazonian Riverside Populations, In Vitro Assays, and In Silico Analyses.

Mercury is one of the most toxic substances found in nature and can be harmful to both the environment and human health. The brain is a critical organ that is sensitive to mercury exposure, especially during development, when it can cause neurological dysfunction and abnormalities as well as other neurodevelopmental deficits. In this context, the identification of new biomarkers of mercury exposure and intoxication will provide valuable tools for the prevention, response, and treatment of environmental contamination. In this study, we propose biotinidase activity as a biomarker of effect, which may provide a direct measure of mercury intoxication, by performing a complete screening in silico, in vitro, and in vivo in human blood samples. Biotinidase is an enzyme that is responsible for the recycling of biocytin. A deficiency of biotinidase is an autosomal recessive disorder that has a variable clinical expression, including delays in development. We evaluated biotinidase activity in the blood of Amazonian riverine populations environmentally exposed to mercury compared to those not exposed. Also, in vitro, other metals were tested to verify the mercury specificity and selectivity for the inhibition of the biotinidase activity. An in silico molecular docking analysis of the target enzyme was performed to understand the preference of methylmercury for the catalytic site. We found that mercury exposure decreases serum biotinidase activity, while other metals do not change it. The molecular docking analysis of the active site indicated a high level of interaction with nucleophiles, with the thiol and selenic groups forming strong bonds with mercury, which implies that cysteine is a potential target for the inhibitory action of mercury. Overall, the evidence indicates that biotinidase activity may serve as a novel biomarker of effect for the assessment of mercury intoxication, which constitutes a persistent threat to both the environment and human populations in the Amazon region.