Second-order rate constants were determined in D2O for deprotonation of acetamide, N,N-dimethylacetamide, and acetate anion by deuterioxide ion and for deprotonation of acetamide by quinuclidine. The values of k(B) = 4.8 x 10(-8) m(-1) s(-1) for deprotonation of acetamide by quinuclidine (pK(BH) = 11.5) and k(BH) = 2-5 x 10(9) M-1 s(-1) for the encounter-limited reverse protonation of the enolate by protonated quinucildine give pK(a)(C) = 28.4 for ionization of acetamide as a carbon acid. The limiting value of k(HOH) = 1 x 10(11) s(-1) for protonation of the enolate of acetate anion by solvent water and k(HO) = 3.5 x 10(-9) M-1 s(-1) for deprotonation of acetate anion by HO- give pK(a)(C) approximate to 33.5 for acetate anion, The change in the rate-limiting step from chemical proton transfer to solvent reorganization results in a downward break in the slope of the plot of log k(HO) against carbon acid pK(a) for deprotonation of a wide range of neutral a-carbonyl carbon acids by hydroxide ion, from -0.40 to -1.0. Good estimates are reported for the stabilization of the carbonyl group relative to the enol tautomer by electron donation from alpha-SEt, alpha-OMe, alpha-NH2, and alpha-O- substituents. The alpha-NH2 and alpha-OMe groups show similar stabilizing interactions with the carbonyl group, while the interaction of alpha-O- is only 3.4 kcal/mol more stabilizing than for alpha-OH, We propose that destabilization of the enolate intermediates of enzymatic reactions results in an increasing recruitment of metal ions by the enzyme to provide electrophilic catalysis of enolate formation.