Malate dehydrogenase cytosolic

In pigeon, chicken, and rabbit liver, phospho-enolpymvate carboxykinase is a mitochondrial enzyme, and phosphoenolpyruvate is transported into the cytosol for gluconeogenesis. In the rat and the mouse, the enzyme is cytosolic. Oxaloacetate does not cross the mitochondrial inner membrane it is converted to malate, which is transported into the cytosol, and convetted back to oxaloacetate by cytosolic malate dehydrogenase. In humans, the guinea pig, and the cow, the enzyme is equally disttibuted between mitochondria and cytosol. 

In common with cholesterol synthesis described in the next section, fatty acids are derived from glucose-derived acetyl-CoA. In the fed state when glucose is plentiful and more than sufficient acetyl-CoA is available to supply the TCA cycle, carbon atoms are transported out of the mitochondrion as citrate (Figure 6.8). Once in the cytosol, citrate lyase forms acetyl-CoA and oxaloacetate (OAA) from the citrate. The OAA cannot re-enter the mitochondrion but is converted into malate by cytosolic malate dehydrogenase (cMDH) and then back into OAA by mitochondrial MDH (mMDH) Acetyl-CoA remains in the cytosol and is available for fatty acid synthesis. 

Compartmentalization of Citric Acid Cycle Components Isocitrate dehydrogenase is found only in the mitochondrion, but malate dehydrogenase is found in both the cytosol and mitochondrion. What is the role of cytosolic malate dehydrogenase ... 

OAA is unable to directly cross the inner mitochondrial membrane it must first be reduced to malate by mitochondrial malate dehydrogenase. Malate can be transported from the mitochondria to the cytosol, where it is reoxidized to oxaloacetate by cytosolic malate dehydrogenase (see Figure 10.3). 

In animals and fungi there is a similar dichotomy. NADPH can be generated by cytosolic malic enzyme which catalyses the reaction malate + NADP+ — pyruvate + COg + NADPH. Cytosolic malate derives from the following successive reactions the pyruvate/ citrate shuttle on the mitochondrial inner membrane takes pyruvate to the mitochondrion in exchange for citrate cytosolic ATP citrate lyase catalyses ATP + citrate + CoA-SH —> acetylCoA (CH3CO-S-C0A) + oxaloacetate and cytosolic malate dehydrogenase, which catalyses NADH + oxaloacetate NAD+ + malate. This scheme provides both acetylCoA and NADPH for subsequent long chain fatty acid synthesis (see section on Fatty acid synthesis ). 

A FIGURE 8-10 The malate shuttle. This cyclical series of reactions transfers electrons from NADH in the cytosol (intermembrane space) across the inner mitochondrial membrane, which is impermeable to NADH itself. StepH Cytosolic malate dehydrogenase transfers electrons from cytosolic NADH to oxaloacetate, forming malate. StepH An antiporter (blue oval) in the inner mitochondrial membrane transports malate into the matrix in exchange for a-ketoglutarate. StepH Mitochondrial malate dehydrogenase converts malate back to oxaloacetate, reducing NAD in the matrix to NADH in the process. StepH Oxaloacetate, which cannot directly cross the inner membrane, is converted to... 

Fig. 8. Pathways involved in the conversion of glucose to fatty acid. Reaction (1) is catalyzed by cytosolic malate dehydrogenase. Reaction (2) is catalyzed by mitochondrial malate dehydrogenase. (T) designates tricarboxylate anion transporter. Reactions catalyzed by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the pentose phosphate pathway produce NADPH. CS, citrate synthase ACL, ATP citrate lyase PDH, pyruvate dehydrogenase complex ACC, acetyl-CoA carboxylase FAS, fatty acid synthase.

P. A. Fields, E. L. Rudomin and G. N. Somero, Temperature sensitivities of cytosolic malate dehydrogenases from native and invasive species of marine mussels (genus Mytilus) sequence-function linkages and correlations with biogeographic distribution, J. Exp. Biol, 2006, 209, 656-667. 

A more complex and more efficient shutde mechanism is the malate-aspartate shuttle, which has been found in mammalian kidney, liver, and heart. This shuttle uses the fact that malate can cross the mitochondrial membrane, while oxaloacetate cannot. The noteworthy point about this shuttle mechanism is that the transfer of electrons from NADH in the cytosol produces NADH in the mitochondrion. In the cytosol, oxaloacetate is reduced to malate by the cytosolic malate dehydrogenase, accompanied by the oxidation of cytosolic NADH to NAD+ (Figure 20.24). The malate then crosses the mitochondrial membrane. In the mitochondrion, the conversion of malate back to oxaloacetate is catalyzed by the mitochondrial malate dehydrogenase (one of the enzymes of the citric acid cycle). Oxaloacetate is converted to aspartate, which can also cross the mitochondrial membrane. Aspartate is converted to oxaloacetate in the cytosol, completing the cycle of reactions. 

Little is known about the NADH aitd NAD content of the cytosol. In order to estimate the NADH/NAD ratio, the cytosolic contents of malate, aspartate, glutamate and 2-oxoglutarate were determined by nonaqueous fractionation of spinach leaves (Table l). From these values the NADH/NAD ratio was calculated on the reasonable assumption that the reactions catalyzed by the cytosolic malate dehydrogenase and glutamate oxaloacetate transaminase are near to equilibrium. Introducing the equilibrium constants of these enzymes 2.8. 10 at pH 7.0 (4), Kqqt... 

Cytosolic malate dehydrogenase transfers the electrons and protons from NADH to oxaloacetate forming malate. Malate enters the mitochondrion via the dicarboxylate carrier in exchange for... 

Figure 3. Model showing possible fates for lipid and carbohydrate carbon during nitrogen assimilation in P. tricomutum. Ruxes shown do not represent actual stoichiometries. (1) glutamine synthetase (2) nitrite reductase (3) nitrate reductase (4) malate glycolysis (5) cytosolic malate dehydrogenase (6) anaplerotic carbon flux (7) gluconeogenesis (8) glycolysis (9) carnitine acyltransferase (10) isocitrate lyase.

Petruccioli M, Angiani E, Eederici E (1996) Semi continuous fumaric acid production by Rhizopus arrhizus immobilized in polymethane sponge. Process Biochem 31 463 69 Pines O, Shemesh S, Battat E, Goldberg I (1997) Overexpression of cytosolic malate dehydrogenase (MDH2) causes overproduction of specific organic acids in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 48 248-255... 

These findings support the idea of a proteolytic mechanism for cata-bolite inactivation. The extremely high sensitivity of cytosolic malate dehydrogenase, in contrast to its mitochondrial isoenzyme, against proteolysis by the yeast proteinases A and B (7) also supports this idea. 

Fahien, L.A., Laboy, J.I., Din, Z.Z., et al., 1999. Ability of cytosolic malate dehydrogenase and lactate dehydrogenase to increase the ratio of NADPH to NADH oxidation by cytosolic giycerol-3-phosphate dehydrogenase. Arch. Biochem. Biophys. 364,185-194. 

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