The Glyoxylate Cycle:-The Glyoxylate Cycle Produces Four-Carbon Compounds from Acetate
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 phospho enolpyruvate for carbohydrate synthesis. In these or ganisms, enzymes of the glyoxylate cycle catalyze the net conversion of acetate to succinate or other four carbon intermediates of the citric acid cycle:
2 Acetyl – CoA + NAD+ + 2H2O → succinate + 2CoA+ NADH + H+
In the glyoxylate cycle, acetyl-CoA condenses with oxaloacetate to form citrate, and citrate is converted to isocitrate, exactly as in the citric acid cycle. The next step, however, is not the breakdown of isocitrate by iso citrate dehydrogenase but the cleavage of isocitrate-by-isocitrate lyase, forming succinate and glyoxylate. The glyoxylate then condenses with a second molecule of acetyl-CoA to yield malate, in a reaction catalyzed by malate synthase. The malate is subsequently oxidized to oxaloacetate, which can condense with another molecule of acetyl-CoA to start another turn of the cycle (Fig. 16–20). Each turn of the glyoxylate cycle consumes two molecules of acetyl-CoA and produces one molecule of succinate, which is then available for bio synthetic purposes. The succinate may be converted through fumarate and malate into oxaloacetate, which can then be converted to phosphoenolpyruvate by PEP carboxykinase, and thus to glucose by gluconeogenesis. Vertebrates do not have the enzymes specific to the glyoxylate cycle (isocitrate lyase and malate synthase) and therefore cannot bring about the net synthesis of glucose from lipids.
In plants, the enzymes of the glyoxylate cycle are sequestered in membrane-bounded organelles called glyoxysomes, which are specialized peroxisomes (Fig. 16–21). Those enzymes common to the citric acid and glyoxylate cycles have two isozymes, one specific to mitochondria, the other to glyoxysomes. Glyoxysomes are not present in all plant tissues at all times. They develop in lipid-rich seeds during germination, before the developing plant acquires the ability to make glucose by photosynthesis. In addition to glyoxylate cycle enzymes, glyoxysomes contain all the enzymes needed for the degradation of the fatty acids stored in seed oils (see Fig. 17–13). Acetyl-CoA formed from lipid breakdown is converted to succinate via the glyoxylate cycle, and the succinate is exported to mitochondria, where citric acid cycle enzymes transform it to malate. A cytosolic isozyme of malate dehydrogenase oxidizes malate to oxaloacetate, a precursor for gluconeogenesis. Germinating seeds can therefore convert the carbon of stored lipids into glucose.
FIGURE 16–20 Glyoxylate cycle. The citrate synthase, aconitase, and malate dehydrogenase of the glyoxylate cycle are isozymes of the citric acid cycle enzymes; isocitrate lyase and malate synthase are unique to the glyoxylate cycle. Notice that two acetyl groups (pink) enter the cycle and four carbons leave as succinate (blue). The glyoxylate cycle was elucidated by Hans Kornberg and Neil Madsen in the laboratory of Hans Krebs.
