Talk:Malate dehydrogenase

message: From the article:
"Because malate dehydrogenase is closely tied to the citric acid cycle, regulation is highly dependent on TCA products. High malate concentrations stimulate MDH activity, and, in a converse manner, high oxaloacetate concentrations inhibit the enzyme[11]. Citrate can both allosterically activate and inhibit the enzymatic activity of MDH. It inhibits the oxidation of malate when there are low levels of malate and NAD+. However, in the presence of high levels of malate and NAD+, citrate can stimulate the production of oxaloacetate. It is believed that there is an allosteric regulatory site on the enzyme where citrate can bind to and drive the reaction equilibrium in either direction[12]."
Direction of reaction is governed by the equilibrium constant, which in turn is a function of the standard free energy change ΔG°'.
Allosteric regulation or no allosteric regulation, enzymes can change the rate of reaction, but can't change the net direction of reaction. (A. Fersht, Structure and Mechanism In Protein Science, Freeman 3rd Ed 1999, top of p.118).  Direction change in this instance is a function of malate and NAD+ concentrations, not allosteric regulation.  96.54.32.44 (talk) 06:23, 1 March 2011 (UTC)
thread_title:  Allosteric regulation and equilibrium 

message: Mechanism of Malate Dehydrogenase is pH Dependent
Malate dehydrogenase interaction with substrate is mediated and dependent on pH level. When malate dehydrogenase binds to oxaloacetate and coenzymes to form a complex, a higher pH is required. Formation of MDH-NADH complex with binding of L-malate requires a higher pH and a histidine moiety on the MDH. Specifically, the protonated histidine can form a hydrogen bond with the substrate's carbonyl oxygen, which shifts electron density away from the oxygen and makes it more susceptible to nucleophilic attack by hydride. As a result, the unprotonated form the MDH-NADH complex binds more favorably to L-malate. In contrast, binding of D-malate and hydroxymalonate to MDH-NADH complex requires a lower pH. Additionally, the protonated form of MDH-NADH complex has a higher affinity for D-malate and hydroxymalonate. [1]
A More Detailed Mechanism of Malate Dehydrogenase
The substate malate is oriented to the active site of malate dehydrogenase in such a way that the hydrogen bonding between malate's carboxylate oxygen atom and the guanidinium functional groups on the sides chains of Arg-81 and Arg-153 on MDH help to stabilize and facilitate the proton and hydride transfer between the substrate and enzyme. These hydrogen bonds remain constant throughout the process. The catalytic mechanism is described as sequential, with the transfer of proton from malate to malate dehydrogenase occurring before the the hydride transfer from malate to NAD+, resulting in the formation of NADH. [8]
Malate + NAD -> NADH + Oxaloacetate
More Details on Regulation of Malate Dehydrogenase
Glutamate has been shown to inhibit malate dehydrogenase activity. Furthermore, it has been shown that alpha ketogluturate dehydrogenase can interact with mitochondrial aspartate aminotransferase to form a complex, which can then bind to malate dehydrogenase, forming a ternary complex that reverses inhibitory action on malate dehydrogenase enzymatic activity by glutamate. [6]Additionally, the formation of this complex enables glutatmate to react with aminotransferase without interfering activity of malate dehydrogenase. The binding of malate dehydrogenase has been shown to increase reaction rate because the Km of malate dehydrogenase is decreased when bound as part of this complex.  — Preceding unsigned comment added by KevinHuai (talk • contribs) 23:57, 14 February 2017 (UTC)
thread_title:  Outline for Malate Dehydrogenase