Gluconeogenesis pathway

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. 

Why aren t the glycolysis and gluconeogenesis pathways the exact reverse of one another ... 

The gluconeogenesis pathway shown as part of the essential pathways of energy metabolism. The numbered reactions are unique to gluconeogenesis. (See Figure 8.2, p. 90 for a more detailed view of the metabolic map.)... 

Activities of Some of the Liver Enzymes that Control the Fluxes in the Glycolysis-Gluconeogenesis Pathways... 

Eight enzyme-catalyzed reactions are involved in the conversion of acetyl-CoA into fatty acids. The first reaction is catalyzed by acetyl-CoA carboxylase and requires ATP. This is the reaction that supplies the energy that drives the biosynthesis of fatty acids. The properties of acetyl-CoA carboxylase are similar to those of pyruvate carboxylase, which is important in the gluconeogenesis pathway (see chapter 12). Both enzymes contain the coenzyme biotin covalently linked to a lysine residue of the protein via its e-amino group. In the last section of this chapter we show that the activity of acetyl-CoA carboxylase plays an important role in the control of fatty acid biosynthesis in animals. Regulation of the first enzyme in a biosynthetic pathway is a strategy widely used in metabolism. 

Figure 18.1 Glucose and lactate traffic in the human organism. Abbreviations glu, glucose gly, glycogen lac, lactate pyr, pyruvate Krebs, Krebs cycle. Pyr is converted to lac, and vice versa, through lactate dehydrogenase (LDH). Although the action of LDH is reversible, the conversions shown indicate only the more prevalent direction. Pyr can be converted to glu via the gluconeogenesis pathway in the liver. Dotted arrow indicates a minor pathway.

The gluconeogenesis pathway is summarized in Figure 18.8. Note that both the mitochondria and cytosol are involved. In the mitochondria, pyruvate is carboxylated by PC to oxaloacetate, as shown in Equation (18.6) ... 

Figure 18.8 Gluconeogenesis pathway in the liver. PC is pyruvate carboxylase PEPCK is phosphoenolpyruvate carboxykinase. (Reproduced by permission from ViduesJ, Sovik O. Gluconeogenesis in infancy and childood. Acta Paediatr Scand 65 307-312, 1976.)...

Two of the molecules that were assayed for in pig serum are often used to assess overall liver function. Name these two molecules. Using your knowledge of the gluconeogenesis pathway and the urea cycle, explain how increased or decreased levels of these two molecules could be used to assess the overall function of the liver. 

Glycerol kinase (which converts glycerol to glycerol 3-phosphate) is a hver enzyme in this way glycerol enters the gluconeogenesis pathway. 

A smaller number of amino acids are degraded to acetyl-CoA or acetoacetyl-CoA. Neither acetyl-CoA nor acetoacetyl-CoA can yield a net production of oxaloacetate, the precursor for the gluconeogenesis pathway (because for every 2-carbon acetyl residue entering the TCA cycle, two carbon atoms leave as CO2). These are referred to as the ketogenic amino acids they can be catabolised for energy in the TCA cycle, or converted to ketone bodies or fatty acids, but they caimot be converted to glucose. 

Just as fatty acids are catabolized and anabolized by different pathways, so too are carbohydrates. Gluconeogenesis, the anabolic pathway by which organisms make glucose from pyruvate, is related to glycolysis but is not its exact reverse. The gluconeogenesis pathway is shown in Figure 29.9 (p. 1222). 

The gluconeogenesis pathway for biosynthesis of glucose frorn pyruvate. The individual steps are explained in more detail in the text. 

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