MDH

Related Reading

MDH is an enzyme that catalyzes the interconversion between malic acidand oxaloacetic acid mainly by using NAD⁺/NADH as a cofactor. Despite the unfavorablereaction to form oxaloacetic acid under standard thermodynamic conditions, MDHis still mainly involved in the oxidation of TCA cycle (conversion of malicacid to oxaloacetic acid). Therefore, it has been proposed that the enzyme hasother functions in the cell. MDH can participate in the reducing TCA cycle toresist oxidative stress, and can also participate in the transport ofsubstrates through metabolic pathways. The MDH of E. coli grown under anaerobicconditions participates in the reducing TCA cycle (converting oxaloacetic acidto malic acid), producing succinic acid. In addition, because oxaloacetatebinds to free radicals, it participates in protection against oxidative stress.MDH from Pseudomonas fluorescens, malic enzyme and pyruvate carboxylase areinvolved in the antioxidant pathway that converts antioxidant NADH toantioxidant NADPH.

Figure 1. Protein structure of MDH.

Introductions

TheMDH protein in some microorganisms can interact with other TCA cycle enzymes topromote substrate channelization, thereby increasing activity. For example, inBacillus subtilis, MDH interacts with two TCA cycle enzymes (isocitratedehydrogenase and citrate synthase) to form metabolites. It has also beenreported that MDH from E. coli interacts with complex I of the respiratorychain to directly transfer NADH. Several eukaryotic MDH isoforms have beenfound in different organelles, and they are involved in multiple metabolicpathways. In bacteria, MDH isoforms are classified according to their cofactorspecificity or the number of subunits. There are two types of MDH isoforms inM. thermophilus. One of them is specific to NAD⁺ and catalyzes the mutualconversion of malic acid and oxaloacetic acid. The other isoform can use NAD⁺ or NADP⁺, butonly catalyzes the reduction of oxaloacetic acid. Two MDH subtypes have beenidentified for Bacillus sphaericus 2R, palustris f-8pt and Bacillus cereusD-402. Dimer isoforms participate in the TCA cycle, and tetramer isoformsparticipate in the glyoxylate cycle.

Functionof malate dehydrogenase

MDHis an enzyme that catalyzes the interconversion between malic acid and oxaloaceticacid mainly by using NAD⁺/NADHas a cofactor. Despite the unfavorable reaction to form oxaloacetic acid understandard thermodynamic conditions, MDH is still mainly involved in theoxidation of TCA cycle (conversion of malic acid to oxaloacetic acid). For thisreason, it has been proposed that the enzyme has other functions in the cell.MDH can participate in the reducing TCA cycle to resist oxidative stress, andcan also participate in the transport of substrates through metabolic pathways.The MDH of E. coli grown under anaerobic conditions participates in thereducing TCA cycle (converting oxaloacetic acid to malic acid), producingsuccinic acid. In addition, since oxaloacetate binds to free radicals, itparticipates in the protection against oxidative stress. MDH from Pseudomonasfluorescens, malic enzyme and pyruvate carboxylase are involved in theantioxidant pathway that converts the antioxidant NADH to the antioxidantNADPH.

Figure 2. Generalreaction showing malate dehydrogenase catalyzed oxidation of malate throughreduction of NAD+.

Regulation

Studieshave shown that excess oxaloacetate and NADH strongly inhibit MDH activity. Insome cases, high concentrations of malic acid will inhibit the reduction ofoxaloacetate. The high concentration of oxalate acetate also inhibited the MDHsof archaea, Rhodobacter halodurans and Rhodosporidium. NADH has the sameinhibitory effect in Myceliophthora thermophila, Aspergillus flavus and E. coli.

Transcriptionalregulation of MDH gene

Theexpression of mdh gene is inhibited by carbon catabolism in several organisms.Among thermophilic thermophilic bacteria, MDH has a higher expression levelwhen grown as a carbon source on malic acid instead of glucose. In addition,under aerobic conditions, the pyruvate-expressed E. coli mdh content is 4 timeshigher than glucose. When staphylococcus grows in glucose, the expressionremains constant, while when grows in fructose, the expression is induced. mdhexpression can also be regulated by transcription factors. In E. coli, theexpression is down-regulated by aerobic respiration control protein (ArcA),especially under anaerobic conditions. When E. coli is grown on an acid medium,it not only increases MDH activity, but also increases isocitrate Dehydrogenaseand succinate dehydrogenase activities.