ENZYME-CATALYZED TRANSFORMATIONS OF COMPOUNDS CONTAINING THE -CH2-ASO3H2 GROUP

Enzymes that act on substrates R-O-PO3H2 often work on substrate analo gues R-O-AsO3H2; such substrates are unstable, since esters of H3AsO4 hydrolyse easily. They also form easily, so that an enzyme that acts o n 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 for med; for example, a stable and active aspartate aminotransferase forms from the apoenzyme with free pyridoxal and arsenate. Enzymes that con vert R-O-PO3H2 into a diester often act on R-CH2-AsO3H2, a stable subs trate analogue; then the product is unstable and hydrolyses to re-form the analogue, giving a futile cycle. For example, RNA polymerase acqu ires exonuclease activity in the presence of H2O3P-CH2-AsO3H2; adenyla te kinase acquires ATPase activity in the presence of the arsonomethyl analogue of AMP. A recent observation is that HO-CH2-CHOH-CH2-CH2-AsO 3H2 is a good substrate for glycerol-3-phosphate dehydrogenase. The pr oduct is unstable and eliminates arsenite, sharing this ability with o ther 3-oxoalkylarsonates. Thus this enzyme-catalysed oxidation is a le thal synthesis, in view of the toxicity of arsenite. Another unusual b iochemical reaction of an arsonic acid is seen in the ability of a bac terium to use arsonoacetate as its sole source of carbon and energy. I n contrast with the elimination of arsenite by 3-oxoalylarsonic acids, 3-oxoalkylphosphonic acids, R-CO-CH2-CH2-PO3H2, are stable. 2-Oxoalky lphosphonic 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, yi elding arsenate. (C) 1997 by John Wiley & Sons, Ltd.