Glyoxylate cycle malate dehydrogenase

Glyoxysomes do not contain all the enzymes needed to run the glyoxylate cycle succinate dehydrogenase, fumarase, and malate dehydrogenase are absent. Consequently, glyoxysomes must cooperate with mitochondria to run their cycle (Figure 20.31). Succinate travels from the glyoxysomes to the mitochondria, where it is converted to oxaloacetate. Transamination to aspartate follows... 

The formation of acetyl-CoA from pyruvate in animals is via the pyruvate dehydrogenase complex, which catalyzes the irreversible decarboxylation reaction. Carbohydrate is synthesized from oxaloacetate, which in turn is synthesized from pyruvate via pyruvate carboxylase. Since the pyruvate dehydrogenase reaction is irreversible, acetyl-CoA cannot be converted to pyruvate, and hence animals cannot realize a net gain of carbohydrate from acetyl-CoA. Because plants have a glyoxylate cycle and animals do not, plants synthesize one molecule of succinate and one molecule of malate from two molecules of acetyl-CoA and one of oxaloacetate. The malate is converted to oxaloacetate, which reacts with another molecule of acetyl-CoA and thereby continues the reactions of the glyoxylate cycle. The succinate is also converted to oxaloacetate via the enzymes of the citric acid cycle. Thus, one molecule of oxaloacetate is diverted to carbohydrate synthesis and, therefore, plants are able to achieve net synthesis of carbohydrate from acetyl-CoA. 

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 ( ). 

Oxaloacetate is formed in the glyoxylate, citric acid, and urea cycles as a result of catalysis by malate dehydrogenase ... 

Fumarate is an intermediate of the citric acid cycle and the glyoxylate cycle, produced by action of the enzyme succinate dehydrogenase on succinate. FADH2 is produced from FAD in the reaction. Fumarate is converted to L-malate by addition of water to the molecule catalyzed by the enzyme fumarate hydratase. 

Malate dehydrogenase is an enzyme of the citric acid cycle, urea cycle, and glyoxylate cycle... 

Fig. 2. (A) The glyoxylate cycle as a bypass of the TCA cycle (after Komberg and Krebs, 1957). (B) The glyoxylate cycle as it functions in the glyoxysome, showing the production of succinate from 2 mol of acetyl-CoA. The five steps constituting the cycle are catalyzed by the following enzymes (1) citrate synthetase, (2) aconitase, (3) isocitrate lyase, (4) malate synthetase, (5) malate dehydrogenase.

From the fact that the glyoxylate and TCA cycles have several enzymes (citrate synthetase, aconitase, malate dehydrogenase) in common it appeared axiomatic that they must operate together in the same intracellular compartment, the mitochondrion. Early experiments with crude particulate pellets containing mitochondria gave only partial support to this view since, although malate synthetase was present in such preparations, most of the isocitrate lyase was present in the supernatant fraction (Yamamoto and Beevers, 1961 Marcus and Velasco, 1960). 

Oxaloacetic acid, the starter compound of both the TCA and the glyoxylate cycles is regenerated from malic acid under the action of malate dehydrogenase. In green plants, oxaloacetic acid can normally be supplied in any amount needed for operation of the cycles from phosphoenol pyruvate. Oxaloacetic acid is the initial product of CO2 fixation in C4-photosynthetic and Crassulacean acid pathways. In these pathways, oxaloacetic acid is formed by yff-carboxylation of phosphoenol pyruvate catalyzed by phosphoenol pyruvate carboxylase. 

The main purpose of the glyoxylate cycle (Figure 12.7) which is located in glyoxysomes of plants is the synthesis of succinate from which carbohydrate may be produced. The reaction sequence utilizes organelle-specific isoenzymes of three enzymes of the tricarboxylate cycle citrate synthase, aconitate hydratase and malate dehydrogenase. These enzymes together with two enzymes... 

Malic acid is mainly produced as an acidulant and taste enhancer in the beverage and food industries. The most preferred metabolic pathway for malate production starts from glucose and proceeds with the carboxylation of pyruvate, followed by the reduction of oxaloacetate to malate. These pathways have been identified in bacterial, yeast, and fungal species (Werpy et al., 2004). In the microalgae reduction of oxaloacetate to malate by NADP malate dehydrogenase (Ouyang et al., 2013 Kuo et al., 2013), the condensation of oxaloacetate and acetyl-coenzyme A (acetyl-CoA) to citric acid is followed by oxidation steps of the tricarboxylic acid (TC A) cycle or glyoxyl-ate shunt to malate (Steinhauser et al., 2012 Pearce et al., 1969 Woodward and Merrett, 1975). 

---