InterPro: IPR012301 Malic enzyme, N-terminal

Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate [1], a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis [2]. There are 3 forms of the enzyme [3]: an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form [2]. Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase [4]; and the hypothetical Saccharomyces cerevisiae protein YKL029c.

Studies on the duck liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity [5]. The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate-or divalent metal ion-binding in the active site [5]. Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme [5], although it is absent in the sequences from some species.

There are three well conserved regions in the enzyme sequences. Two of them seem to be involved in the binding NAD or NADP. The significance of the third one, located in the central part of the enzymes, is not yet known.