Gluconeogenesis pyruvate

It is clear that, to avoid metabolic chaos, biosynthetic pathways cannot use the same enzyme machinery as the corresponding catabolic ones. Sometimes, as in the synthesis of glucose from pyruvate (gluconeogenesis), this implies the use of alternative enzymes for only a few specific steps in the pathway, sometimes, as in the biosynthesis of fatty acids, the pathway is localised in a different cellular compartment from the catabolic pathway, and uses different enzymes. We now discuss each of these pathways in turn. 

Propionyl-CoA is converted to succinyl-CoA, which is oxidized or converted to glucose by way of oxaloacetate and pyruvate (gluconeogenesis Chapter 15). Succinyl-CoA may also form. 5-aminolevulinate, a precursor of porphyrin biosynthesis (Chapter 29). Formation of succinyl-CoA from propionyl-CoA requires three mitochondrial enzymes and two vitamins (Figure 18-5). 

Many of the reactions involved in the synthesis of glucose from pyruvate—gluconeogenesis—are carried out by the same enzymes that catalyze the reactions in glycolysis— they are just operating in reverse. 

Pyruvate carboxylase is the most important of the anaplerotie reactions. It exists in the mitochondria of animal cells but not in plants, and it provides a direct link between glycolysis and the TCA cycle. The enzyme is tetrameric and contains covalently bound biotin and an Mg site on each subunit. (It is examined in greater detail in our discussion of gluconeogenesis in Chapter 23.) Pyruvate carboxylase has an absolute allosteric requirement for acetyl-CoA. Thus, when acetyl-CoA levels exceed the oxaloacetate supply, allosteric activation of pyruvate carboxylase by acetyl-CoA raises oxaloacetate levels, so that the excess acetyl-CoA can enter the TCA cycle. 

FIGURE 23.1 The pathways of gluconeogenesis and glycolysis. Species in blue, green, and peach-colored shaded boxes indicate other entry points for gluconeogenesis (in addition to pyruvate). 

FIGURE 23.5 Pyruvate carboxyl compartmentalized reaction. Pyruva verted to oxaloacetate in the mitoci Because oxaloacetate cannot be trai across the mitochondrial membrant reduced to malate, transported to tl and then oxidized back to oxaloace gluconeogenesis can continue. 

Acetyl-CoA is a potent allosteric effector of glycolysis and gluconeogenesis. It allosterically inhibits pyruvate kinase (as noted in Chapter 19) and activates pyruvate carboxylase. Because it also allosterically inhibits pyruvate dehydrogenase (the enzymatic link between glycolysis and the TCA cycle), the cellular fate of pyruvate is strongly dependent on acetyl-CoA levels. A rise in... 

Step 1 of Figure 29.13 Carboxylation Gluconeogenesis begins with the carboxyl-afion of pyruvate to yield oxaloacetate. The reaction is catalyzed by pyruvate carboxylase and requires ATP, bicarbonate ion, and the coenzyme biotin, which acts as a carrier to transport CO2 to the enzyme active site. The mechanism is analogous to that of step 3 in fatty-acid biosynthesis (Figure 29.6), in which acetyl CoA is carboxylated to yield malonyl CoA. 

Biomolecules are synthesized as well as degraded, but the pathways for anabolism and catabolism are not the exact reverse of one another. Fatty acids are biosynthesized from acetate by an 8-step pathway, and carbohydrates are made from pyruvate by the 11-step gluconeogenesis pathway. 

Mechanism for Gluconeogenesis. Since the glycolysis involves three energetically irreversible steps at the pyruvate kinase, phosphofructokinase, and hexokinase levels, the production of glucose from simple noncarbohydrate materials, for example, pyruvate or lactate, by a reversal of glycolysis ( from bottom upwards ) is impossible. Therefore, indirect reaction routes are to be sought for. 

The free glucose produced by this reaction is supplied to the blood from the tissues. As exemplified by gluconeogenesis, one may easily envision the economical organization of these metabolic routes, since, apart from four special gluconeogenesis enzymes-pyruvate carboxylase, phosphopyruvate carboxylase, fructose bisphosphatase, and glucose 6-phosphatase-individual glycolytic enzymes are also used in the gluconeogenesis. 

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