Acetyl-CoA-glyoxylate cycle

An acetyl-CoA-glyoxylate cycle, which catalyzes oxidation of acetyl groups to glyoxylate, can also be constructed from isocitrate lyase and citric acid cycle... 

At the bottom of Fig. 17-18 several stages of the a-oxo acid elongation process are arranged in tandem. We see that glyoxylate (a product of the acetyl-CoA-glyoxylate cycle) can be built up systematically to... 

FIGURE 20.28 The glyoxylate cycle. The first two steps are identical to TCA cycle reactions. The third step bypasses the C09-evolving steps of the TCA cycle to produce snc-cinate and glyoxylate. The malate synthase reaction forms malate from glyoxylate and another acetyl-CoA. The result is that one torn of the cycle consumes one oxaloacetate and two acetyl-CoA molecnles bnt produces two molecnles of oxaloacetate. The net for this cycle is one oxaloacetate from two acetyl-CoA molecnles. 

Another model is based on the fact that the genetic code shows a number of regularities, some of which have already been mentioned above. It is suspected that codons beginning with C, A or U code for amino acids which were formed from a-ketoacids (or a-ketoglutarate, 1-KG), oxalacetate (OAA) and pyruvate. This new model, which is quite different from the previous models, assumes that a covalent complex formed from two nucleotides acted as a catalyst for chemical reactions such as the reductive amination of a-ketoacids, pyruvate and OAA. More recent analyses suggest that the rTCA cycle (see Sect. 7.3) could have served as a source of simple a-ketoacids, including glyoxylate, pyruvate, OAA and a-KG. a-Ketoacids could, however, also have been formed via a reductive acetyl-CoA reaction pathway. The bases of the two nucleotides specify the amino acid synthesized and were retained until the modern three-letter codes were established (Copley et al., 2005). 

Fig. 9. Pathway duplication the methyl citrate cycle and the glyoxylate shunt. A pathway for acetate metabolism in E. coli that uses the glyoxylate shunt is depicted on the right. Part of the methyl citrate cycle, a pathway for propionate metabolism, is depicted on the left. The pathways are analogous furthermore, three of the four steps are catalyzed by homologous enzymes. PrpE (propionyl-CoA synthase) is homologous to AcsA (acetyl-CoA synthase). PrpC (2-methyl-citrate synthase) is homologous to GltA (citrate synthase). PrpB (2-methyl-isocitrate lyase) is homologous to AceA (isocitrate lyase). The third step in the methyl citrate cycle has been suggested to be catalyzed by PrpD the second half of the reaction (the hydration) can be catalyzed by aconitase.

Using the so-called glyoxylic acid cycle, plants and bacteria are able to convert acetyl-CoA into succinate, which then enters the tricarboxylic acid cycle. For these organisms, fat degradation therefore functions as an anaplerotic process. In plants, this pathway is located in special organelles, the glyoxysomes. 

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. 

Vertebrates lack the glyoxylate cycle and cannot synthesize glucose from acetate or the fatty acids that give rise to acetyl-CoA. 

Plants can synthesize sugars from acetyl-CoA, the product of fatty acid breakdown, by the combined actions of the glyoxylate cycle and gluconeogenesis. 

Some bacteria use a "dicarboxylic acid cycle" to oxidize glyoxylate OHC-COO to C02. The regenerating substrate for this cycle is acetyl-CoA. It is synthesized from glyoxylate by a complex pathway that begins with conversion of two molecules of glyoxylate to tartronic semialdehyde ... 

As mentioned in Section 4, glyoxylate can be converted to oxaloacetate by condensation with acetyl-CoA (Fig. 17-16) and the oxaloacetate can be decarboxylated to pyruvate. This sequence of reactions resembles that of the conversion of oxaloacetate to 2-oxoglutarate in the citric acid cycle (Fig. 17-4). Doth... 

Certain microorganisms have a modification of this cycle in which isocitric acid is cleaved to succinic acid and glyoxylic acid. The latter acid is condensed with acetyl-CoA to form malic acid. In this modification (the glvoxvlic acid cvcle), oxalsuccinic acid and alpha-ketoglularic acid are not involved. This is sometimes referred to as the glyoxylate shunt pathway. 

The glyoxylate cycle permits growth on a two-carbon source. The glyoxylate cycle bypasses the two steps of the TCA cycle in which C02 is released. Furthermore, two molecules of acetyl-CoA are taken in per turn of the cycle rather than just one, as in the TCA cycle. The net result is the conversion of two mole-... 

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

The FADH2 and NADH produced feed directly into oxidative phosphorylation, while the acetyl CoA feeds into the citric acid cycle where further FADH2 and NADH are produced. In animals the acetyl CoA produced in 13-oxidation cannot be converted into pyruvate or oxaloacetate, and cannot therefore be used to make glucose. However, in plants two additional enzymes allow acetyl CoA to be converted into oxaloacetate via the glyoxylate pathway. 

Some plants and bacteria that can use acetate as their sole source of carbon are able to oxidize acetyl-CoA via the citric acid cycle, or the acetate can be converted to carbohydrates via a pathway that is a modification of the citric acid cycle. This pathway is known as the glyoxylate cycle (Fig. 12-10)... 

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