Glyoxylate cycle succinate

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... 

Isocitrate Lyase Short-Circuits the TCA Cycle by Producing Glyoxylate and Succinate... 

In plants, certain invertebrates, and some microorganisms (including E. coli and yeast) acetate can serve both as an energy-rich fuel and as a source of phosphoenolpyruvate for carbohydrate synthesis. In these organisms, enzymes of the glyoxylate cycle catalyze the net conversion of acetate to succinate or other four-carbon intermediates of the citric acid cycle ... 

FIGURE 16-22 Relationship between the glyoxylate and citric acid cycles. The reactions of the glyoxylate cycle (in glyoxysomes) proceed simultaneously with, and mesh with, those of the citric acid cycle (in mitochondria), as intermediates pass between these compartments. The conversion of succinate to oxaloacetate is catalyzed by citric acid cycle enzymes. The oxidation of fatty acids to acetyl-CoA is described in Chapter 17 the synthesis of hexoses from oxaloacetate is described in Chapter 20. 

A key enzyme in the glyoxylate cycle is isocitrate lyase, which cleaves isocitrate (Eq. 13-40) to succinate and glyoxylate. The latter is condensed with a second acetyl group by the action of malate synthase (Eq. 13-38). The L-malate formed in this reaction is dehydrogenated to the regenerating substrate oxalo-... 

Glyoxylate cycle. A pathway that uses acetyl-CoA and two auxiliary enzymes to convert acetate into succinate and carbohydrates. 

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. 

Many bacteria and plants are able to subsist on acetate or other compounds that yield acetyl CoA. They make use of a metabolic pathway absent in most other organisms that converts two-carbon acetyl units into four-carbon units (succinate) for energy production and biosyntheses. This reaction sequence, called the glyoxylate cycle, bypasses the two decarboxylation steps of the citric acid cycle. Another key difference is that two molecules of acetyl CoA enter per turn of the glyoxylate cycle, compared with one in the citric acid cycle. 

In plants, these reactions take place in organelles called glyoxysomes. Succinate, released midcycle, can be converted into carbohydrates by a combination of the citric acid cycle and gluconeogenesis. Thus, organisms with the glyoxylate cycle gain a metabolic versatility. 

Succinate dehydrogenase (also called succinate-coenzyme Q reductase or Complex II) is an enzyme of the citric acid cycle and glyoxylate cycle that catalyzes the reaction below ... 

Succinate is an intermediate of the citric acid cycle (and the glyoxylate cycle) produced by action of the enzyme succinyl-CoA synthetase on succinyl-CoA. Succinate is converted to fumarate by action of the enzyme succinate dehydrogenase (with formation of FADH2)... 

Glyoxylate is a two carbon compound generated in the glyoxylate cycle by action of the enzyme isocitrate lyase on isocitrate (the other product of the reaction is succinate). Glyoxylate is combined with acetyl-CoA to form malate by the enzyme malate synthase. 

The glyoxylate cycle (Figure 17.21), like the citric acid cycle, begins with the condensation of acetyl CoA and oxaloacetate to form citrate, which is then isomerized to isocitrate. Instead of being decarboxylated, isocitrate is cleaved by isocitrate lyase into succinate and glyoxylate. The subsequent steps regenerate oxaloacetate from glyoxylate. Acetyl CoA condenses with... 

FIGURE 17.21 The glyoxylate pathway. The glyoxylate cycle allows plants and some microorganisms to grow on acetate because the cycle bypasses the decarboxylation steps of the citric acid cycle. The enzymes that permit the conversion of acetate into succinate-isocitrate lyase and malate synthase-are boxed in blue. 

In plants, the synthesis of succinate from acetyl CoA in the glyoxylate cycle generates NADH. Glyoxysomes do not have an electron transport chain. Suggest a way in which NADH could be reoxidized in a plant cell so that the glyoxylate cycle can continue. 

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