Malate dehydrogenase, function

The standard free-energy change for this reaction is quite high, but under physiological conditions (including a very low concentration of oxaloacetate) AG 0 and the reaction is readily reversible. Mitochondrial malate dehydrogenase functions in both gluconeogenesis and the citric acid cycle, but the overall flow of metabolites in the two processes is in opposite directions. 

Because of the fairly conclusive evidence that malate synthesized by dark CO2 fixation is not in equilibrium with malate synthesized in the mitochondria, it seems reasonable to conclude that the soluble malate dehydrogenase functions to a large extent in the dark CO2 fixation pathway. We also would predict, that insofar as P-enolpyruvate carboxylase-mediated synthesis of malate takes place in chloroplasts, the NADP malate dehydrogenase would be the coupling enzyme. 

J. Muller, M.-F. Manent, and G. Pfleiderer, Importance of tyrosine for structure and function of mitochondrial malate dehydrogenases, Biochim. Biophys. Acta 742, 189-196 (1983). 

A key structural and mechanistic feature of lactate and malate dehydrogenases is the active site loop, residues 98-110 of the lactate enzyme, which was seen in the crystal structure to close over the reagents in the ternary complex.49,50 The loop has two functions it carries Arg-109, which helps to stabilize the transition state during hydride transfer and contacts around 101-103 are the main determinants of specificity. Tryptophan residues were placed in various parts of lactate dehydrogenase to monitor conformational changes during catalysis.54,59,60 Loop closure is the slowest of the motions. 

Figure 6.5. Compatibility of organic osmolytes with enzyme function. (Upper panel) Pyruvate kinase of the marine crab Pachygrapsus crassipes. The effects of KC1 and NaCI and several organic solutes on the Km of phosphoenol pyruvate (PEP) (modified after Bowlus and Somero, 1979). (Middle panel) Malate dehydrogenase of the mangrove (Rhizophora mangle). Effects of NaCI and three organic osmolytes (the amino acid proline and the polyols pinitol and OMMI) on catalytic activity (modified after Sommer et al., 1990). (Bottom panel) Effects of NaCI and four osmolytes found in mammalian kidney (urea, glycine betaine, sorbitol, and inositol) on the Km of uric acid of uricase (modified after Yancey, 1992). (Figure modified after Somero and Yancey, 1997.)...

It is not the purpose of this review to provide a comprehensive account of these structure-function studies however, the case of citrate synthase will be described briefly to illustrate the potential of such investigations. The studies on malate dehydrogenase are reviewed by Eisenberg et al. [81], and those on glyceraldehyde 3-phosphate dehydrogenase are described in detail in Chapter 7. 

Special Function of Lactate Dehydrogenase Special Fimction of Malate Dehydrogenase Ketone Bodies... 

Lipoxygenase Malate dehydrogenase Metallo-endopeptidase N-Methyl transferase Monoamine oxidase Mixed-function oxidase (cytochrome P450 dependent) NADH2 diaphorase NADPH2 diaphorase Neutral endopeptidase 24.11 Nitro oxide synthase Nitro reductase 5 -Nucleotidase Peroxidase... 

Tripathi, A. K., Desai, P. V., Pradhan, A., Khan, S. I., Avery, M. A., Walker, L. A., and Tekwani, B. L. (2004). An alpha-proteobacterial type malate dehydrogenase may complement LDH function in Plasmodium falciparum. Cloning and biochemical characterization of the enzyme. Eur.. Biochem. 271,3488-3502. 

Their acute toxicity to mammals is low, but the two active substances may cause dermatitis. In rats fed daily on a diet containing quinomethionate a high cumulative toxicity was observed. A dietary level of 500 mg/kg for 90 days reduced body-weight, caused hypertrophy of the liver, and inhibited acetoacetate synthesis and the microsomal enzymes. It primarily inhibited the function of the HS-enzymes (pyruvate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and a-ketoglutarate oxidase) (Carlson and DuBois, 1970). 

The soluble isozyme is generally considered to take part in the cytoplasmic side of the malate shuttle, providing a means of transporting NADH equivalents, in the form of malate, across the mitochondrial membrane. The mitochondrial enzyme, in addition to its role in the other half of the malate shuttle, is also a necessary component of the tricarboxylic acid cycle. The microbody malate dehydrogenase found in some plants appears to function in the glyoxylate cycle (5) or possibly in photorespiration ( ). 

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