Human lactate dehydrogenase and malate dehydrogenase possess the catalytic properties to produce aromatic α-hydroxy acid

Abstract

Lactate dehydrogenase and malate dehydrogenase are the two main alpha-hydroxy acid dehydrogenases in the human body. We investigated the catalytic properties of human lactate dehydrogenase LDHC, LDHL6A and malate dehydrogenase MDH1 on aromatic α-keto acids phenylpyruvic acid, p-hydroxyphenylpyruvic acid and 3,4-dihydroxyphenylpyruvic acid. The optimum temperatures for LDHC, LDHL6A, and MDH1 are 37 °C, 35 °C, and 45 °C, respectively; and the optimum pH is 6.5, 6.5, and 5.5, respectively. The K _m of LDHC for phenylpyruvic acid and 3,4-dihydroxyphenylpyruvic acid were 0.90 mM and 0.92 mM, respectively. LDHL6A has a high affinity for phenylpyruvic acid and 3,4-dihydroxyphenylpyruvic acid with K _m of 0.77 mM and 0.80 mM, respectively; MDH1 has an extremely high affinity (K _m = 0.46 mM) and catalytic efficiency (k _cat/K _m = 23.87 s⁻¹·mM⁻¹) for p-hydroxyphenylpyruvic acid. It also has a high affinity for 3,4-dihydroxyphenylpyruvic acid with a K _m of 0.90 mM, but with a low affinity for phenylpyruvic acid (K _m = 3.76 mM). The catalytic properties of human LDHC, LDHL6A, and MDH1 for the abovementioned aromatic α-keto acids may be one of the sources of L-phenyllactic acid, L-p-hydroxyphenyllactic acid, and L-3,4-dihydroxyphenyllactic acid in humans.