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. Author manuscript; available in PMC: 2020 Dec 1.
Published in final edited form as: J Biol Inorg Chem. 2019 Nov 21;24(8):1305–1316. doi: 10.1007/s00775-019-01740-8

Figure 1. iAs metabolism.

Figure 1.

(a) Arsenite (iAsIII) enters the cells through aqua(glycerol)porins (AQP) and the glucose transporters (GLUT), while arsenate (iAsV) does it through phosphate transporters. iAs is methylated through different mechanisms: (b) Oxidative methylation refers to the reduction of iAsV to iAsIII by the thioredoxin (Trx) / trx reductase (TR) system, and its subsequent methylation by the arsenite methyltransferase (AS3MT). Monomethyl arsonous acid (MMAIII), monomethylarsonic acid (MMAV); dimethylarsinous acid (DMAIII) and dimethylarsinic acid or cacodylic acid (DMAV) are the metabolites formed, (c) The glutathione (GSH) conjugation mechanism is based on the formation of GSH complexes with AsIII resulting in the formation of arsenic triglutathione [As(GS)3] by glutathione S-transferases (GSTs). The As(GS)3 is subsequently methylated by AS3MT to form monomethylarsinic GSH [MMA(GS)2] and dimethylarsinic GSH [DMA(GS)]. (d) iAs metabolites are exported through the multidrug resistance proteins (MRP1, MRP2 or MRP4)