Glutamine gluconeogenesis

Martin, G., B. Ferrier, A. Conjard, M. Martin, R. Nazaret, M. Boghossian, F. Saade, C. Mancuso, D. Durozard and G. Baverel, 2007. Glutamine gluconeogenesis in the small intestine of 72h-fasted adult rats is undetectable. Biochem. J. 401,465-473. 

Stumvoll, M., C. Meyer, M. Kreider, G. Perriello and J. Gerich, 1998 Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. Metabolism 47, 1227-12232. 

Major amino acids emanating from muscle are alanine (destined mainly for gluconeogenesis in liver and forming part of the glucose-alanine cycle) and glutamine (destined mainly for the gut and kidneys). 

Gluconeogenesis glutamine and glutamate metabolism. Part synthesis of vitamin D. 

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

Gluconeogenesis. The gluconeogenic pathway is present in the kidney, as in the liver. Thus, amino acids (and lactate) can be converted to glucose in the kidney but a major precursor, in acidotic conditions, is glutamine. 

Figure 8.30 Different roles of periportal and perivenous cells in the liver in respect of glutamine metabolism. Glutamine is converted to glucose in periportal cells via gluconeogenesis in perivenous cells, ammonia is taken up, to form glutamine, which is released into the blood. This emphasises the importance of the liver in removing ammonia from the blood, i.e. if possesses two process to ensure that all the ammonia is removed.

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 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.

Figure 32-3. Schematic representation of fuel mobilization during fasting. Catabolism of muscle proteins provides alanine for gluconeogenesis and glutamine for utilization by the gut and kidney, while branched chain amino acids are primarily oxidized within the muscle. Breakdown of adipocyte triacylglycerols provides glycerol and free fatty acids (not shown) the free fatty acids provide fuel for liver, muscle and most other peripheral tissues. The liver utilizes both alanine and glycerol to synthesize glucose which is required for the brain and for red blood cells (not shown). Adapted from Besser and Thirner (2002).

The mitochondrial translocators which have been most carefully assessed with respect to their role in control of metabolism are (1) the adenine nucleotide translocator with respect to its role in the control of respiration (2) the liver pyruvate transporter and the control of gluconeogenesis and (3) kidney glutamate and glutamine transport and their control of ammoniagenesis. 

A. Pyruvate is converted in mitochondria to malate, which can cross the mitochondrial membrane. Oxaloacetate and acetyl CoA cannot. Lactate is produced from pyruvate in the cytosol. The reverse reaction is involved in gluconeogenesis. Glutamine is not derived from pyruvate during gluconeogenesis. 

---