ARSENITE RELEASE ON ENZYMATIC TRANSFORMATION OF ARSONOMETHYL SUBSTRATE-ANALOGS - A POTENTIALLY LETHAL SYNTHESIS BY GLYCEROL-3-PHOSPHATE DEHYDROGENASE

The isosteric arsenical analogue of glycerol 3-phosphate, 3,4-dihydrox ybutylarsonic acid, is a good substrate for rabbit muscle glycerol-3-p hosphate dehydrogenase. Its oxidation is accompanied by release of ars enite. This release seems to be due to a spontaneous elimination of ar senite by 3-oxoalkylarsonic acids, as it is also observed in (1) the o xidation of 3-hydroxypropylarsonic acid by yeast alcohol dehydrogenase , (2) treatment of 3,4-dihydroxybutylarsonic acid with periodate and ( 3) non-enzymic transamination of the glutamate analogue 2-amino-4-arso nobutyric acid. Enzymic formation of 3-oxoalkylarsonic acids in cells can therefore be lethal, as arsenite is poisonous to most organisms be cause of its high affinity for dithiols such as dihydrolipoyl groups.