Identification of morin and other compounds as inhibitors of the malic enzyme of Mucor circinelloides in vitro but not in vivo

Abstract

Of 13 compounds tested, 11 inhibited malic enzyme activity in Mucor circinelloides, to some degree, at 5 mM. Four of these inhibitors (tartronic acid, morin, catechin and 2,5-dihydroxybenzoic acid) were studied further. Tartronic acid, morin and catechin were competitive inhibitors of malic enzyme (with respect to malate), with apparent K_i values of 0.04 mM, 5 μM and 0.6 mM, respectively. 2,5-Dihydroxybenzoic acid was a non-competitive inhibitor, with respect to malate, and had an apparent K_i value of 0.8 mM. Morin and tartronic acid did not inhibit any other NADPH-generating enzyme studied, although both inhibited malate dehydrogenase. The inhibitory actions of catechin and 2,5-dihydroxybenzoic acid were less specific. All four compounds inhibited malic enzyme, to some extent, when included in the culture medium. This inhibition was not as great as in vitro however and was insufficient to have an effect on lipid metabolism in M. circinelloides.