ESTERASE-LIKE ACTIVITY OF HUMAN SERUM-ALBUMIN TOWARD PRODRUG ESTERS OF NICOTINIC-ACID

The esterase-like activity of human serum albumin (HSA) toward esters of nicotinic acid was investigated under a variety of conditions such as protein concentration, temperature, FH, ionic strength, nature of b uffers, and presence of organic solvents. Initial rate constants of hy drolysis of 18 nicotinates in the presence of 50 mu M HSA were measure d at pH 7.4 and 37 degrees C. The substrates displayed half-lifes rang ing from less than 15 min (2-butoxyethyl nicotinate) to more than 95 h r (methyl nicotinate). The hydrolysis of tert-butyl nicotinate was too slow to be measurable, whereas 1-carbamoylethyl nicotinate was stabil ized against hydrolysis by the presence of HSA. The rate constants of HSA-catalyzed hydrolysis were well correlated (r(2) = 0.85; N = 12) wi th previously published data obtained in human plasma, indicating simi lar substrate specificities in the two biological preparations, All ev idence points to serum albumin as the possible major catalyst of hydro lysis of nicotinate esters in human plasma.