Gluconeogenesis pathway for

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

FIGURE 20.7 Carbon chains of the 20 common amino acids are converted into one of seven intermediates for further breakdown in the citric acid cycle. Ketogenic amino acids (red) can also enter the pathway for fatty-acid biosynthesis glucogenic amino acids (blue) can also enter the gluconeogenesis pathway for glucose biosynthesis. 

The gluconeogenesis pathway for the biosynthesis of giucose from pyruvate, individuai steps are expiained in the text. 

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. 

The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. It also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the hver is the only tissue in which all occur to a significant extent. The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue (as in cirrhosis). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported such ab-normahties would be incompatible with life or normal development. 

The citric acid cycle is not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substtates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it fimctions in both oxidative and synthetic processes, it is amphibolic (Figure 16—4). 

Fig. 5. The metabolic pathway for glycolysis and gluconeogenesis. (A) An illustration of overall reactions among key compounds. (B) The enzymes responsible for the reactions are denoted in rectangles with the EC numbers inside. The two shaded enzymes are key enzymes that regulate the overall direction of glycolysis or gluconeogenesis.

The pathway for gluconeogenesis is shown in Figures 6.23 and 6.24. Some of the reactions are catalysed by the glycolytic enzymes i.e. they are the near-equilibrium. The non-equilibrium reactions of glycolysis are those catalysed by hexokinase (or glucokinase, in the liver), phosphofructokinase and pyruvate kinase and, in order to reverse these steps, separate and distinct non-equilibrium reactions are required in the gluconeogenic pathway. These reactions are ... 

FIGURE 20-35 Conversion of stored fatty acids to sucrose in germinating seeds. This pathway begins in glyoxysomes. Succinate is produced and exported to mitochondria, where it is converted to oxaloacetate by enzymes of the citric acid cycle. Oxaloacetate enters the cytosol and serves as the starting material for gluconeogenesis and for the synthesis of sucrose, the transport form of carbon in plants. 

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.)... 

Hydrolysis of fructose 1,6-bisphosphate by fructose 1,6-bispho -phatase bypasses the irreversible phosphofructokinase-1 reaction, and provides an energetically favorable pathway for the formation of fructose 6-phosphate (Figure 10.4). This reaction is an important regulatory site of gluconeogenesis. 

The rest of the Calvin cycle is involved in interconversion of carbohydrates to make glucose (or starch) and the regeneration of the ribulose-bisphosphate acceptor. The reactions are also found in the pathways for gluconeogenesis and the pentose phosphate shunt (see Volume 1, Chapters 10 and 12). The first step is the phosphorylation of 3-phosphoglycerate by the same reactions involved in gluconeogenesis. 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

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.

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. 

The glucocorticoid cortisol is secreted from the adrenal cortex as a stress response under the control of adrenocorticotropic hormone (ACTH, corticotropin) produced by the anterior pituitary. Cortisol promotes catabolism by inducing synthesis of specific proteins. Cortisol binds to a cytosolic cortisol receptor which then translocates to the nucleus and switches on the expression of specific genes, notably that for PEP carboxykinase (PEPCK). Cortisol-induced expression of the key gluconeogenesis enzyme PEPCK increases levels of the enzyme and hence increases gluconeogenesis and available blood glucose. The cAMP-and cortisol-mediated pathways for induction of PEPCK expression are further linked by CREB-dependent expression of a coactivator protein PGC-1 that promotes cortisol-dependent expression of PEPCK. 

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. 

Table I. Subset of Pathways for Biosynthesis of Glucose and Intemediates During Gluconeogenesis from [3-Alanine...

---