Gluconeogenesis and

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). 

Pilkis, S. J., El-Maghrabi, M. R., and Claus, T. H., 1988. Hormonal regulation of hepatic gluconeogenesis and glycolysis. Annual Review of Biochemistry 57 755-783. 

Succinyl-CoA is converted to succinate by the enzyme succinate thiokinase (succinyl-CoA synthetase). This is the only example in the citric acid cycle of substrate-level phosphorylation. Tissues in which glu-coneogenesis occurs (the hver and kidney) contain two isoenzymes of succinate thiokinase, one specific for GDP and the other for ADP. The GTP formed is used for the decarboxylation of oxaloacetate to phos-phoenolpymvate in gluconeogenesis and provides a regulatory hnk between citric acid cycle activity and the withdrawal of oxaloacetate for gluconeogenesis. Nongluconeogenic tissues have only the isoenzyme that uses ADP. 

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). 

Pilkis SJ, Granner DK Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol... 

Dextrose used in PN compounding typically is provided as a 70% stock solution (70 g/100 mL), although some institutions use a 50% stock solution. The final dextrose concentration in the PN solution typically should not exceed 35%. Hydrous dextrose provides 3.4 kcal/g (14.2 kj/g). A dextrose infusion rate of 2 mg/kg per minute should be sufficient to suppress gluconeogenesis and prevent protein breakdown in adults.5 Continuous dextrose infusion rate in adult patients generally should not exceed 4 to 5 mg/kg per minute in most hospitalized patients.6,7... 

Low glucose levels turn on gluconeogenesis and protein degradation. 

Between meals when fatty acids are oxidized in the liver for energy, accumulating acetyl CoA activates pyruvate carboxylase and gluconeogenesis and inhibits PDH, thus preventing conversion of lactate and alanine to acetyl CoA. 

Glycerol may be picked up by liver and converted to dihydroxyacetone phosphate (DHAP) for gluconeogenesis, and the fetty adds are distributed to tissues that can use them. Free fatty acids are transported through the blood in association with serum albumin. 

The FADHj and NADH are oxidized in the electron transport chain, providing ATP. In musde and adipose tissue, the acetyl CoA enters the citric acid cyde. In liver, the ATP may be used for gluconeogenesis, and the acetyl CoA (which cannot be converted to glucose) stimulates gluco-neogenesis by activating pyruvate carboxylase. 

Figure 21.20 Diagram of a tori q/de in a patient with a tumour. Lactate produced from glucose by tumour cells is converted back to glucose in the liver (gluconeogenesis) and released into the blood for re-uptake by tumour cell, an ATP-reguiring process. Note that muscle, immune cells and red blood cells will also contribute to the cycle (see. Chapter 6 Figure 6.10).

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