The uncatalysed and metal-ion catalysed decarboxylation of 3-oxoglutaric acid: a model for an enzyme system

Abstract

The uncatalysed decarboxylation of 3-oxoglutaric acid, HO2C·CH2·CO·CH2·CO2H → CH3·CO·CH2·CO2H + CO2 has been studied at 42°. The rate constants for the un-ionised acid, the monoanion, and the dianion are 12 × 10–3 min–1, 45 × 10–3 min–1, and 2·75 × 10–3 min–1 respectively. Because of the higher reactivity of the monoanion, the pH-rate profile for the uncatalysed decarboxylation is bell-shaped with a rate maximum at pH 3·5 (l= 0·1M). The enhanced reactivity of the monoanion appears to be due to intramolecular hydrogen bonding between the carbonyl group and the un-ionised carboxy-group. The practical ionisation constants of 3-oxoglutaric acid are pK1= 3·23 and pK2= 4·27 at 0·01M. The decarboxylation of 3-oxoglutaric acid, unlike that of acetoacetic acid, is catalysed by transition-metal ions, so that in the presence of metal ions there is a rapid loss of one molecular equivalent of carbon dioxide followed by a slower loss of a second molecular equivalent in the uncatalysed reaction. The catalytic effects of copper(II), nickel(II), and manganese(II) have been studied in some detail. It has been found that 2,2′-bipyridyl which is capable of π-bonding with the metal ions enhances the catalytic activity of manganese(II) by a factor of 10 while the effect with copper(II) and nickel(II) is less marked (ca. 2 times). The possible significance of these effects in the action of the metal-activated decarboxylases is discussed, as manganese(II) is the biologically important metal ion in the enzymatic reactions.