Enzymatic Reduction of Arsenic Compounds in Mammalian Systems:  The Rate-Limiting Enzyme of Rabbit Liver Arsenic Biotransformation Is MMAV Reductase

• Published in: Chemical research in toxicology Vol. 12; no. 12; pp. 1278 - 1283
• Main Authors: Zakharyan, Robert A, Aposhian, H. Vasken
• Format: Journal Article
• Language: English
• Published: American Chemical Society 20-12-1999
• DOI: 10.1021/tx9901231
• EISSN: 1520-5010
• ISSN: 0893-228X

A unique enzyme, MMAV reductase, has been partially purified from rabbit liver by using DEAE-cellulose, carboxymethylcellulose, and red dye ligand chromatography. The enzyme is unique since it is the rate-limiting enzyme in the biotransformation of inorganic arsenite in rabbit liver. The K m and V max values were 2.16 × 10-3 M and 10.3 μmol h-1 (mg of protein)-1. When DMAV or arsenate was tested as a substrate, the K m was 20.9 × 10-3 or 109 × 10-3 M, respectively. The enzyme has an absolute requirement for GSH. Other thiols such as DTT or l-cysteine were inactive alone. At a pH below the physiological pH, GSH carried out this reduction, but this GSH reduction in the absence of the enzyme had little if any value at pH 7.4. When the K m values of rabbit liver arsenite methyltransferase (5.5 × 10-6 M) and MMAIII methyltransferase (9.2 × 10-6) were compared to that of MMAV reductase (2.16 × 10-3 M), it can be concluded that MMAV reductase was the rate-limiting enzyme of inorganic arsenite biotransformation. MMAV reductase was also present in surgically removed human liver.