25400-23-1Relevant articles and documents
Enzymatic reduction of arsenic compounds in mammalian systems: The rate- limiting enzyme of rabbit liver arsenic biotransformation is MMA(V) reductase
Zakharyan, Robert A.,Aposhian, H. Vasken
, p. 1278 - 1283 (1999)
A unique enzyme, MMA(v) 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 x 10-3 M and 10.3 μmol h-1 (mg of protein)-1. When DMA(v) or arsenate was tested as a substrate, the K(m) was 20.9 x 10-3 or 109 x 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 x 10-6 M) and MMA(III) methyltransferase (9.2 x 10-6) were compared to that of MMA(v) reductase (2.16 x 10-3 M), it can be concluded that MMA(v) reductase was the rate-limiting enzyme of inorganic arsenite biotransformation. MMA(v) reductase was also present in surgically removed human liver.
Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats
Suzuki,Tomita,Ogra,Ohmichi
, p. 1604 - 1611 (2001)
The metabolic pathways for arsenic were precisely studied by determining the metabolic balance and chemical species of arsenic to gain an insight into the mechanisms underlying the animal species difference in the metabolism and preferential accumulation of arsenic in red blood cells (RBCs) in rats. Male Wistar rats were injected intravenously with a single dose of arsenite (iAsIII) at 2.0 mg of As/kg of body weight, and then the time-dependent changes in the concentrations of arsenic in organs and body fluids were determined. Furthermore, arsenic in the bile was analyzed on anion and cation exchange columns by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). The metabolic balance and speciation studies revealed that arsenic is potentially transferred to the hepato-enteric circulation through excretion from the liver in a form conjugated with glutathione (GSH). iAsIII is methylated to mono (MMA)- and dimethylated (DMA) arsenics in the liver during circulation in the conjugated form [iAsIII(GS)3], and a part of MMA is excreted into the bile in the forms of MMAIII and MMAv, the former being mostly in the conjugated form [CH3AsIII(GS)2], and the latter being in the nonconjugated free form. DMAIII and DMAv were not detected in the bile. In the urine, arsenic was detected in the forms of iAsIII, arsenate, MMAv, and DMAv, iAsIII being the major arsenic in the first 6-h-urine, and DMAv being increased in the second 6-h-urine. The present metabolic balance and speciation study suggests that iAsIII is methylated in the liver during its hepato-enteric circulation through the formation of the GSH-cojugated form [iAsIII(GS)3], and MMAIII and MMAv are partly excreted into the bile, the former being in the conjugated form [CH3AsIII(GS)2]. DMA is not excreted into the bile but into the bloodstream, accumulating in RBCs, and then excreted into the urine mostly in the form of DMAv in rats.
