Malate dehydrogenase cytosol

The second electron shuttle system, called the malate-aspartate shuttle, is shown in Figure 21.34. Oxaloacetate is reduced in the cytosol, acquiring the electrons of NADH (which is oxidized to NAD ). Malate is transported across the inner membrane, where it is reoxidized by malate dehydrogenase, converting NAD to NADH in the matrix. This mitochondrial NADH readily enters the electron transport chain. The oxaloacetate produced in this reaction cannot cross the inner membrane and must be transaminated to form aspartate, which can be transported across the membrane to the cytosolic side. Transamination in the cytosol recycles aspartate back to oxaloacetate. In contrast to the glycerol phosphate shuttle, the malate-aspartate cycle is reversible, and it operates as shown in Figure 21.34 only if the NADH/NAD ratio in the cytosol is higher than the ratio in the matrix. Because this shuttle produces NADH in the matrix, the full 2.5 ATPs per NADH are recovered. 

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. 

The malate-aspartate shuttle is the most important pathway for transferring reducing equivalents from the cytosol to the mitochondria in brain. This shuttle involves both the cytosolic and mitochondrial forms of aspartate aminotransferase and malate dehydrogenase, the mitochondrial aspartate-glutamate carrier and the dicarboxylic acid carrier in brain (Fig. 31-5) [69]. The electrogenic exchange of aspartate for glutamate and a... 

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. 

Malic enzyme (malate dehydrogenase (decarboxylating), EC 1.1.1.39) catalyzes reversible oxidative decarboxylation of malate to pyruvate. The enzyme uses NAD+ as an electron acceptor, but it is also able to utilize NADP+ with lower affinity (Drmota et al. 1996). With a subunit size of approximately 63 kDa, the Trichomonas hydrogenosomal malic enzyme belongs to the family of large, eukaryotic type of malic enzymes. In contrast, the approximately 40-kDa-subunit malic enzyme, located in the cytosol, belongs... 

Because the mitochondrial membrane has no transporter for oxaloacetate, before export to the cytosol the oxaloacetate formed from pyruvate must be reduced to malate by mitochondrial malate dehydrogenase, at the expense of NADH ... 

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). 

Oxaloacetate, the product of the first step in gluconeogenesis, must leave the mitochondrion and enter the cytosol where the subsequent enzyme steps take place. Since the inner mitochondrial membrane is impermeable to oxaloacetate, it is converted to malate by mitochondrial malate dehydrogenase. This leaves the mitochondrion and is converted back to oxaloacetate in the cytosol by cytoplasmic malate dehydrogenase. 

A similar shuttle, the malate-aspartate shuttle, operates in heart and liver (Fig. 6). Oxaloacetate in the cytosol is converted to malate by cytoplasmic malate dehydrogenase, reoxidizing NADH to NAD+ in the process. The malate enters the mitochondrion via a malate-a-ketoglutarate carrier in the inner mitochondrial membrane. In the matrix the malate is reoxidized to oxaloacetate by NAD+ to form NADH. Oxaloacetate does not easily cross the inner mitochondrial membrane and so is transaminated to form aspartate which then exits from the mitochondrion... 

Fig. 5.4. Two types of energy metabolism in cestodes. (a) Type 1 homolactate fermentation, (b) Type 2 Malate dismutation. Reaction 3 involves a carboxylation step decarboxylation occurs at 6, 7 and 10. Reducing equivalents are generated at reactions 6 and 7 one reducing equivalent is used at reaction 9. Thus, when the mitochondrial compartment is in redox balance and malate is the sole substrate, twice as much propionate as acetate is produced. Key 1, pyruvate kinase 2, lactate dehydrogenase 3, phosphoenolpyruvate carboxykinase 4, malate dehydrogenase 5, mitochondrial membrane 6 malic enzyme 7, pyruvate dehydrogenase complex 8, fumarase 9, fumarate reductase 10, succinate decarboxylase complex. indicates reactions at which ATP is synthesised from ADP cyt, cytosol mit, mitochondrion. (After Bryant Flockhart, 1986.)...

Lin, J.J., T.H. Yang, B.D. Wahlstrand, P.A. Fields, and G.N. Somero (2001). Phylogenetic relationships and biochemical properties of the duplicated cytosolic and mitochondrial isoforms of malate dehydrogenase from a teleost fish, Sphyraena idiastes. J. Mol. Evol., in press. 

Answer Malate dehydrogenase catalyzes the conversion of malate to oxaloacetate in the citric acid cycle, which takes place in the mitochondrion, and also plays a key role in the transport of reducing equivalents across the inner mitochondrial membrane via the malate-aspartate shuttle (Fig. 19-29). This shuttle requires the presence of malate dehydrogenase in the cytosol and the mitochondrial matrix. 

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 ). 

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