Malate to Oxaloacetate

In the last reaction of the cycle, L-malate is oxidized to oxaloacetate by malate dehydrogenase, an NAD+-linked enzyme  

The enzyme has absolute specificity for the double bond of the trans-unsaturated acid and for the formation of 

Although the equilibrium of this reaction favors malate formation, in vivo the reaction proceeds toward the formation of oxaloacetate, since the latter is rapidly removed by the citrate synthase reaction to initiate the next round of the cycle. 

---

The fumarate produced in step [4] is converted via malate to oxaloacetate [6, 7], from which aspartate is formed again by transamination [9]. The glutamate required for reaction [9] is derived from the glutamate dehydrogenase reaction [8], which fixes the second NH4 " in an organic bond. Reactions [6] and [7] also occur in the tricarboxylic acid cycle. However, in urea formation they take place in the cytoplasm, where the appropriate isoenzymes are available. 

Oxidation of Malate to Oxaloacetate In the last reaction of the citric acid cycle, NAD-linked L-malate dehydrogenase catalyzes the oxidation of L-malate to oxaloacetate ... 

Succinate Dehydrogenase Catalyzes the Oxidation of Succinate to Fumarate Fumarase Catalyzes the Addition of Water to Fumarate to Form Malate Malate Dehydrogenase Catalyzes the Oxidation of Malate to Oxaloacetate... 

Malate Dehydrogenase Catalyzes the Oxidation of Malate to Oxaloacetate... 

The final oxidation step of the cycle involves the conversion of malate to oxaloacetate by malate dehydrogenase. 

Oxidation of malate to oxaloacetate (catalyzed by malate dehydrogenase the reaction requires NAD+). 

This also occurs in the Krebs cycle, as in the dehydrogenation of malate to oxaloacetate. 

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. 

D. FAD is required for conversion of succinate to fumarate, and NAD+ is required for conversion of malate to oxaloacetate. Five ATP are generated. Coenzyme A is not required, and no isomerization reactions occur. GTP is produced when succinyl CoA is converted to succinate. 

Reminding that the concentration of oxaloacetate must be kept nearly 0 for the synthesis of citrate, malate-to-oxaloacetate reaction may run perpetually even if the concentration ratio [NADH]/[NAD ] is approximately 1 at anaerobic condition. 

The answer is b. (Murray, pp 182-189. Scriver, pp 1521-1552. Sack, pp 121-138. Wilson, pp 287-317.) Reducing equivalents are produced at four sites in the citric acid cycle. NADH is produced by the isocitrate dehydrogenase-catalyzed conversion of a-ketoglutarate to succinyl CoA and by the malate dehydrogenase-catalyzed conversion of malate to oxaloacetate. FADH, is produced by the succinate dehydrogenase-catalyzed conversion of succinate to fumarate. Succinyl CoA synthetase catalyzes the formation of succinate from succinyl CoA, with the concomitant phosphorylation of GDP to GTP... 

Reaction 8. In the final step of the citric acid cycle, malate dehydrogenase catalyzes the reduction of NAD+ to NADH and the oxidation of malate to oxaloacetate. Because the citric acid cycle "began" with the addition of an acetyl group to oxaloacetate, we have come full circle. 

In the oxidation of malate to oxaloacetate, what is the structural evidence that an oxidation reaction has occurred What functional groups are involved ... 

Amino acids that form intermediates of the TCA cycle are converted to malate, which enters the cytosol and is converted to oxaloacetate, which proceeds through gluconeogenesis to form glucose. When excessive amounts of ethanol are ingested, elevated NADH levels inhibit the conversion of malate to oxaloacetate in the cytosol. Therefore, carbons from amino acids that form intermediates of the TCA cycle cannot be converted to glucose as readily. 

After malate or aspartate traverse the mitochondrial membrane (acting as carriers of oxaloacetate) and enter the cytosol, they are reconverted to oxaloacetate by reversal of the reactions given above (see Figs. 31.7B and C). The conversion of malate to oxaloacetate generates NADH. Whether oxaloacetate is transported... 

The conversion of malate to oxaloacetate has a AG° = +7.1 kcal/mol, yet in the citric acid cycle the reaction proceeds from malate to oxaloacetate. Explain how this is possible. 

Mn-SOD is an important antioxidant enzyme for the cell due to its role in detoxifying the free radical species superoxide (Oj), so HNE modification of this protein makes the cell more vulnerable to free radical attack. Alpha enolase facilitates the penultimate step of glycolysis by catalyzing the conversion of 2-phosphoglycerate into phosphoenolpyruvate. With HNE modification of alpha enolase, the cell is at risk of inadequate ATP stores due to inhibited production of pyruvate for fueling the citric acid cycle. Similarly, HNE modification of ATPase can lead to inhibited ATP formation due to the direct role of this enzyme in ATP synthesis. Triose phosphate isomerase catalyzes the reversible conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate in glycolysis and MDH catalyzes the oxidation of malate to oxaloacetate, so HNE modification of these proteins can also lead to lower ATP production. 

Acetyl-CoA is therefore the substrate for two competing reactions with oxaloacetate to form citrate or with acetoacetyl-CoA to form ketone bodies (ketogenesis). Which reaction predominates depends partly on the rate of -oxidation itself and partly on the redox state of the mitochondrial matrix which controls the oxidation of malate to oxaloacetate, hence, the amount of oxaloacetate available to react with acetyl-CoA. The proportion of acetyl groups going into the TCA cycle relative to ketogenesis is often referred to as the acetyl ratio . The overall rate of -oxidation may be controlled by a number of well-known mechanisms ... 

---