Biological Fate of Arsenic Species

Atomic Adsorption Spectroscopy.

Background
How humans and other mammals process and detoxify the toxic inorganic forms of arsenic are beset by conflicting reports, ambiguities and unknowns. Elucidation of the fate of inorganic arsenic in mammals would be expected to lead to a better understanding of the mechanisms of chronic inorganic arsenic poisoning.

Goal
To study the enzymes in the human body that modify the toxicity of arsenic species.

Objectives
1. Purify toxicity modifying enzymes and study their molecular mechanisms of action.

2. Investigate inhibitors of this modification process as a possible way to block conversion to any carcinogenic biotransformant.

3. Investigate glutathione-arsenic complexes and determine the role of glutathione in how arsenic species efflux the cell.

Significant Findings
1. Accomplished purification of enzymes that reduce various forms of Arsenic in the body. More specifically, MMA5 reductase was purified and sequenced. Sequencing indicated that MMA5 reductase and glutathione S transferase omega (GSTO) are identical proteins. The glutathione S transferases are of major importance for metabolizing xenobiotics in humans. GSTO is the newest of the transferases and one of its functions now appears to be reduction of arsenic species.

2. Inhibitors have also been found. These inhibitors block the biotransformation of arsenic but there is uncertainty if the inhibitors block carcinogenicity.

Publications

Contact
H. Vasken Aposhian
aposhian@u.arizona.edu
520-621-7565