Arsenite release on enzymic transformation of arsonomethyl substrate analogues: a potentially lethal synthesis by glycerol-3-phosphate dehydrogenase.
The isosteric arsenical analogue of glycerol 3-phosphate, 3,4-dihydroxybutylarsonic acid, is a good substrate for rabbit muscle glycerol-3-phosphate dehydrogenase. Its oxidation is accompanied by release of arsenite. This release seems to be due to a spontaneous elimination of arsenite by 3-oxoalkylarsonic acids, as it is also observed in (1) the oxidation of 3-hydroxypropylarsonic acid by yeast alcohol dehydrogenase, (2) treatment of 3,4-dihydroxybutylarsonic acid with periodate and (3) nonenzymic transamination of the glutamate analogue 2-amino-4-arsonobutyric acid. Enzymic formation of 3-oxoalkylarsonic acids in cells can therefore be lethal, as arsenite is poisonous to most organisms because of its high affinity for dithiols such as dihydrolipoyl groups.
Mutenda
E K
EK
Department of Biochemistry, University of Cambridge, U.K.
Sparkes
M J
MJ
Dixon
H B
HB
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000613:Aminobutyrates / Q000737:chemistry; D000818:Animals; D001151:Arsenic / Q000737:chemistry; D001152:Arsenicals / Q000138:chemical synthesis / Q000378:metabolism*; D018053:Arsenites / Q000378:metabolism*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D007202:Indicators and Reagents; D007700:Kinetics; D018482:Muscle, Skeletal / Q000201:enzymology*; D010084:Oxidation-Reduction; D010504:Periodic Acid; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013379:Substrate Specificity
C095814:3,4-dihydroxybutylarsonic acid; D000613:Aminobutyrates; D001152:Arsenicals; D018053:Arsenites; D007202:Indicators and Reagents; D010504:Periodic Acid; C038917:2-amino-4-arsonobutanoic acid; C009288:metaperiodate; D005993:Glycerolphosphate Dehydrogenase; D000426:Alcohol Dehydrogenase; C015001:arsenite; D001151:Arsenic