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Pathway Description
Gluconeogenesis
Homo sapiens
Metabolic Pathway
Gluconeogenesis, which is essentially the reverse of glycolysis, results in the sythesis of glucose from non-carbohydrate substrates such as lactate, glycerol, and glucogenic amino acids. In animals, gluconeogenesis occurs primarily in the liver, and in the renal cortex to a lesser extent. This process occurs during periods of fasting or intense exercise. Gluconeogenesis is often associated with ketosis. Several non-carbohydrate carbon substrates can enter the gluconeogenesis pathway. One common substrate is lactic acid, formed during anaerobic respiration in skeletal muscle. Lactate may also come from red blood cells, which obtain energy solely from glycolysis as they have no membrane-bound organelles for aerobic respiration. Lactate is transported to the liver to be converted into pyruvate in the Cori cycle by lactate dehydrogenase. Pyruvate can then be used to generate glucose via gluconeogenesis. Many other compounds can also function as substrates for gluconeogenesis such as citric acid cycle intermediates (through conversion to oxaloacetate), amino acids other than lysine or leucine, and glycerol .
References
Gluconeogenesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM: Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature. 2003 May 29;423(6939):550-5. doi: 10.1038/nature01667. Epub 2003 May 18.
Pubmed: 12754525
Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni OD, Kahn BB, Jain MK: Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab. 2007 Apr;5(4):305-12. doi: 10.1016/j.cmet.2007.03.002.
Pubmed: 17403374
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P: Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005 Mar 3;434(7029):113-8. doi: 10.1038/nature03354.
Pubmed: 15744310
Jager S, Handschin C, St-Pierre J, Spiegelman BM: AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12017-22. doi: 10.1073/pnas.0705070104. Epub 2007 Jul 3.
Pubmed: 17609368
Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P: Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007 Apr 4;26(7):1913-23. doi: 10.1038/sj.emboj.7601633. Epub 2007 Mar 8.
Pubmed: 17347648
Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P: Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008 Jan 9;582(1):46-53. doi: 10.1016/j.febslet.2007.11.034. Epub 2007 Nov 26.
Pubmed: 18036349
Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM: Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab. 2006 May;3(5):333-41. doi: 10.1016/j.cmet.2006.04.002.
Pubmed: 16679291
Mazzucotelli A, Viguerie N, Tiraby C, Annicotte JS, Mairal A, Klimcakova E, Lepin E, Delmar P, Dejean S, Tavernier G, Lefort C, Hidalgo J, Pineau T, Fajas L, Clement K, Langin D: The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human white adipocytes. Diabetes. 2007 Oct;56(10):2467-75. doi: 10.2337/db06-1465. Epub 2007 Jul 23.
Pubmed: 17646210
Kovarova J, Nagar R, Faria J, Ferguson MAJ, Barrett MP, Horn D: Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei. PLoS Pathog. 2018 Dec 27;14(12):e1007475. doi: 10.1371/journal.ppat.1007475. eCollection 2018 Dec.
Pubmed: 30589893
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