Malate dehydrogenase, reaction

A typical intramitochondrial concentration of malate is 0.22 mM. If the [NAD ]/[NADH] ratio in mitochondria is 20 and if the malate dehydrogenase reaction is at equilibrium, calculate the intramitochondrial concentration of oxaloacetate at 25°C. 

In the third step, 1, -/3-hydroxyacyl-CoA is dehydrogenated to form /3-ketoacyl-CoA, by the action of /3-hydroxyacyl-CoA dehydrogenase NAD+ is the electron acceptor. This enzyme is absolutely specific for the l stereoisomer of hydroxyacyl-CoA The NADH formed in the reaction donates its electrons to NADH dehydrogenase, an electron carrier of the respiratory chain, and ATP is formed from ADP as the electrons pass to 02. The reaction catalyzed by /3-hydroxyacyl-CoA dehydrogenase is closely analogous to the malate dehydrogenase reaction of the citric acid cycle (p. XXX). 

However, the urea cycle also causes a net conversion of oxaloacetate to fumarate (via aspartate), and the regeneration of oxaloacetate (Fig. 18-12) produces NADH in the malate dehydrogenase reaction. Each NADH molecule can generate up to 2.5 ATP during mitochondrial... 

Fatty acid biosynthesis (and most biosynthetic reactions) requires NADPH to supply the reducing equivalents. Oxaloacetate is used to generate NADPH for biosynthesis in a two-step sequence. The first step is the malate dehydrogenase reaction found in the TCA cycle. This reaction results in the formation of NAD from NADH (the NADH primarily comes from glycolysis). The malate formed is a substrate for the malic enzyme reaction, which makes pyruvate, CO2, and NADPH. Pyruvate is transported into the mitochondria where pyruvate carboxylase uses ATP energy to regenerate oxaloacetate. 

Oxidation of reduced pyridine nucleotides Reaction with isocitrate dehydrogenase, glucose 6-phosphate dehydrogenase, malate dehydrogenase Reaction with GSH... 

In the citric acid cycle, the malate dehydrogenase reaction... 

The /3-hydroxyacyl-CoA dehydrogenase reaction is analogous to the malate dehydrogenase reaction both are NAD-requiring and act on /3-hydroxyacyl compounds ... 

The final dehydrogenase in the system (malate dehydrogenase, reaction 11) uses NAD as a substrate and, like pyruvate dehydrogenase, responds sharply to... 

As outlined above, Bash et al. concluded that in the similar malate dehydrogenase reaction, proton transfer preceded hydride transfer. 

Niacin is utilized in the synthesis of the nicotinamide portion of NAD, which is used in the isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, and malate dehydrogenase reactions. 

NADH is produced by the a-ketoglutarate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase reactions of the TCA cycle, by the pyruvate dehydrogenase reaction that converts pyruvate to acetyl CoA, by (3-oxidation of fatty acids, and by other oxidation reactions. 

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.

Like all metabolic pathways, the TCA cycle operates with an overall net negative AG° (Fig 20.11). The conversion of substrates to products is, therefore, energetically favorable. However, some of the reactions, such as the malate dehydrogenase reaction, have a positive value. 

Figure 29.1 shows that the high ratio of NADH NAD in the mitochondrion favours reduction of oxaloacetate to malate in the malate dehydrogenase reaction. It also restricts oxidation in the a-ketoglutarate dehydrogenase and isocitrate dehydrogenase reactions. The result is that Krebs cycle is inhibited. 

Oxaloacetate is first reduced to malate by malate dehydrogenase (reaction (9.5)). 

The thermodynamic equilibrium constant for the malate dehydrogenase reaction is about 1.7-10 (Yoshida, 1965) and hence, the overall reaction [see Eq. (4.3)] is practically not reversible. It is not surprising, therefore, that succulent tissues with these enzymes tend to accumulate massive quantities of malic acid ... 

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