Methylarsonous acid transport by aquaglyceroporins

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Mammals detoxify trivalent inorganic arsenic [As(III)] via methylation in the liver.
• Methylated arsenicals are released into circulation and excreted.
• Methylarsonous acid [MAs(III)] is a toxic methylation product of As(III).

Purpose of the Study:

• To investigate the transport of methylarsonous acid [MAs(III)] through aquaglyceroporin channels.
• To compare the transport rates of MAs(III) and As(III) across different aquaglyceroporins.
• To identify key residues in AQP9 involved in MAs(III) translocation.

Main Methods:

• Functional analysis of aquaglyceroporins (GlpF, Fps1p, AQP9) for MAs(III) transport.
• Comparative transport assays for MAs(III) and As(III) using wild-type and mutant AQP9.
• Site-directed mutagenesis to examine the role of AQP9 residues Phe-64 and Arg-219.

Main Results:

• Aquaglyceroporins, including rat AQP9, facilitate the movement of MAs(III).
• Rat AQP9 transports MAs(III) at a higher rate than the yeast homologue Fps1p.
• Rat AQP9 exhibits higher transport rates for MAs(III) compared to As(III).
• Residue Arg-219 in AQP9 appears crucial for MAs(III) transport, similar to As(III).

Conclusions:

• Aquaglyceroporins exhibit differential selectivity and transport rates for trivalent arsenicals.
• MAs(III) utilizes the same translocation pathway as As(III) in rat AQP9.
• Understanding MAs(III) transport via AQP9 is vital for comprehending arsenic physiology in mammals.