Metabolome analysis revealed the critical role of betaine for arsenobetaine biosynthesis in the marine medaka (Oryzias melastigma).

Arsenobetaine (AsB), a non-toxic arsenic (As) compound found in marine fish, structurally resembles betaine (GB), a common methyl donor in organisms. This study investigates the potential role of GB in AsB synthesis in marine medaka (Oryzias melastigma) using metabolomic analysis. Dietary exposure to arsenate (As(V)) and varying GB concentrations (0.05% and 0.1% in diets) increased total As and AsB bioaccumulation, particularly in marine medaka muscle. Metabolomic analysis revealed that GB played a crucial role in promoting up-regulation in methylthioadenosine (MTA) by modulating the methionine cycle and down-regulation in glutathione (GSH) by modulating the glutathione cycle. Methionine metabolism and GSH, potentially binding again to exogenous GB, could synchronously produce more non-toxic AsB. Combining verification experiments of differential metabolites of Escherichia coli in vitro, GB, GSH, S-adenosylmethionine (SAM), and arsenocholine (AsC) entered methionine and glutathione metabolism pathways to generate more AsB. These findings underscore the GB's crucial regulatory role in modulating the synthesis of AsB. This study provides vital insights into the interplay between the structural analogs GB and AsB, offering specific strategies to enhance the detoxification mechanisms of marine fish in As-contaminated environments.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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