Enzyme-catalysed Transformations of Compounds Containing the –CH2-AsO3H2 Group

Enzymes that act on substrates R–O–PO₃H₂ often work on substrate analogues R–O–AsO₃H₂; such substrates are unstable, since esters of H₃AsO₄ hydrolyse easily. They also form easily, so that an enzyme that acts on R–O–PO₃H₂ often acts on a mixture of R–OH and arsenate via an ester that forms at the active site. Similarly coenzyme analogues may be formed; for example, a stable and active aspartate aminotransferase forms from the apoenzyme with free pyridoxal and arsenate. Enzymes that convert R–O–PO₃H₂ into a diester often act on R–CH₂–AsO₃H₂, a stable substrate analogue; then the product is unstable and hydrolyses to re-form the analogue, giving a futile cycle. For example, RNA polymerase acquires exonuclease activity in the presence of H₂O₃P–CH₂–AsO₃H₂; adenylate kinase acquires ATPase activity in the presence of the arsonomethyl analogue of AMP. A recent observation is that HO–CH₂–CHOH–CH₂–CH₂–AsO₃H₂ is a good substrate for glycerol-3-phosphate dehydrogenase. The product is unstable and eliminates arsenite, sharing this ability with other 3-oxoalkylarsonates. Thus this enzyme–catalysed oxidation is a lethal synthesis, in view of the toxicity of arsenite. Another unusual biochemical reaction of an arsonic acid is seen in the ability of a bacterium to use arsonoacetate as its sole source of carbon and energy. In contrast with the elimination of arsenite by 3-oxoalylarsonic acids, 3-oxoalkylphosphonic acids, R–CO–CH₂–CH₂–PO₃H₂, are stable. 2-Oxoalkylphosphonic acids, R–CO–CH₂–PO₃H₂, however, are moderately unstable to hydrolysis, yielding phosphate and R–CO–CH₃. 2-Oxoalkylarsonic acids, R–CO–CH₂–AsO₃H₂, decompose in the same way, but much more readily, yielding arsenate. © 1997 by John Wiley & Sons, Ltd.