Gluconeogenesis Glucogenic

The degradation of most amino acids is anaplerotic, because it produces either intermediates of the cycle or pyruvate glucogenic amino acids see p. 180). Gluconeogenesis is in fact largely sustained by the degradation of amino acids. A particularly important anaplerotic step in animal metabolism leads from pyruvate to oxaloacetic acid. This ATP-dependent reaction is catalyzed by pyruvate... 

With two exceptions (lysine and leucine see below), all of the proteinogenic amino acids are also glucogenic. Quantitatively, they represent the most important precursors for gluconeogenesis. At the same time, they also have an anaplerotic effect—1. e., they replenish the tricarboxylic acid cycle in order to feed the anabolic reactions that originate in it (see p. 138). 

The main precursors of gluconeogenesis in the liver are lactate from anaerobically working muscle cells and from erythrocytes, glucogenic amino acids from the digestive tract and muscles (mainly alanine), and glycerol from adipose tissue. The kidney mainly uses amino acids for gluconeogenesis (Glu, Gin see p.328). 

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

FIGURE 14-19 Alternative paths from pyruvate to phospho-enolpyruvate. The path that predominates depends on the glucogenic precursor (lactate or pyruvate). The path on the right predominates when lactate is the precursor, because cytosolic NADH is generated in the lactate dehydrogenase reaction and does not have to be shuttled out of the mitochondrion (see text). The relative importance of the two pathways depends on the availability of lactate and the cytosolic requirements for NADH by gluconeogenesis. 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

Glucogenic amino acids (see Table 14-4) derived from the breakdown of stored seed proteins also yield precursors for gluconeogenesis, following transamination and oxidation to succinyl-CoA, pyruvate, oxaloacetate, fumarate, and a-ketoglutarate (Chapter 18)—all good starting materials for gluconeogenesis. 

FIGURE 23-28 Fuel metabolism in the liver during prolonged fasting or in uncontrolled diabetes mellitus. After depletion of stored carbohydrates, to proteins become an important source of glucose, produced from glucogenic amino acids by gluconeogenesis. ... 

Answer Muscle proteins are selectively degraded by proteases in myocytes, and the resulting amino acids move, in the bloodstream, from muscle to liver. In the liver, glucogenic amino acids are the starting materials for gluconeogenesis, to provide glucose for export to the brain (which cannot use fatty acids as fuel). 

Figure 10-1. Enzymatic pathways for glucose synthesis from amino acids or pyruvate in mammalian Ever. Enclosed in the boxes are the glucogenic amino acids with arrows indicating the points where carbon skeletons from these amino acids enter the pathways of gluconeogenesis or the tricarboxylic acid cycle. Bracketed next to the rate-controlling enzymes for gluconeogenesis are some of the substances that increase (T) or decrease (1) the activity of these enzymes. 3PG, 3-phosphoglycerate.

Figure 20-4. Biochemical pathways for gluconeogenesis in the liver. Alanine, a major gluconeogenic substrate, is used to synthesize oxaloacetate. The carbon skeletons of glutamine and other glucogenic amino acids feed into the TCA cycle as a-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate and thus also provide oxaloacetate. Conversion of oxaloacetate to phosphoenolpyruvate and ultimately to glucose limits the availability of oxaloacetate for citrate synthesis and thus greatly diminishes flux through the initial steps of the TCA cycle (dashed lines). Concurrent P-oxidation of fatty acids provides reducing equivalents (NADH and FADH2) for oxidative phosphorylation but results in accumulation of acetyl-CoA.

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