Hydrolysis of 2-hydroxy-4-(methylthio)butanoic acid dimer in two model systems

Hydrolysis of 2-hydroxy-4-(methylthio)butanoic acid (HMB) dimer was observed in two model systems that were designed to emulate in vivo conditions. A physiologically feasible rate of hydrolysis of this methionine precursor has not previously been demonstrated in vivo. In the first model, simulated intestinal fluid (SIF) was used, and in the second model, sections of chick small intestine were incubated in vitro with the compound under study. When HMB dimer was incubated with SIF, hydrolysis was very rapid until half of the dimer was hydrolyzed. Subsequent hydrolysis was negligible in that model system. In contrast, hydrolysis neared completion when sections of small intestine were incubated with HMB dimer. These results indicate that studies of HMB dimer cleavage must include consideration of enzymatic hydrolysis factors.