Oxidation of methionine and 2-hydroxy 4-methylthiobutanoic acid stereoisomers in chicken tissues.

Oxidation of DL-2-hydroxy 4-methylthiobutanoic acid (DL-HMB), DL-methionine (DL-MET) and L-methionine (L-MET) in chicken tissue homogenates was compared using 1-14C-labelled tracers. The pattern of oxidation of the substrates was similar at both low (0.7 mM) and high (20 mM) concentrations. The rate of conversion to 2-keto 4-methylthiobutanoic acid (KMB) was highest for DL-MET and lowest for L-MET in kidney, liver and intestinal mucosa. In breast muscle, rates for DL-MET and L-MET were similar at 0.7 mM, but DL-HMB showed the highest rate at 20 mM. Kidney contained the highest specific activity for oxidation of all three substrates. Raising the pH of liver and kidney homogenates from 7.5 to 8.6 increased the oxidation of DL-MET, exclusively. Experiments with inhibitors of D-2-hydroxy acid dehydrogenase (EC 1.1.99.6) and L-2-hydroxy acid oxidase (EC 1.1.3.15) suggested that D- and L-HMB were stereospecifically oxidized by the enzymes. KMB stimulated L-MET oxidation in kidney yet inhibited L-MET oxidation in liver homogenates. The effect of KMB on DL-MET and DL-HMB oxidation also varied between tissues. Amino-oxyacetate inhibited L-MET oxidation completely and DL-MET and DL-HMB oxidation almost completely in both kidney and liver. L-Cycloserine was less potent than amino-oxyacetate and decreased L-MET oxidation more in kidney than in liver. It can be calculated from the results that, at low substrate concentrations, the liver contributes principally to the whole body oxidation of both DL-HMB and DL-MET. At high (greater than physiological) concentrations, DL-HMB would be oxidized principally in skeletal muscle. At all concentrations, L-MET would be converted to KMB mainly in the muscle.