Not to be confused with Glucuronidation, Glycogenesis, Glyceroneogenesis, Glycogenolysis, or Glycolysis.
Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms.[1] In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia).[2] In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc.[3] In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.
In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis (see figure). For the breakdown of proteins, these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol, odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of metabolism that includes lactate from the Cori cycle. Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose.[4] Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting.[5]
The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or GTP, effectively making the process exergonic. For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation.[6]
^Nelson DL, Cox MM (2000). Lehninger Principles of Biochemistry. USA: Worth Publishers. p. 724. ISBN 978-1-57259-153-0.
^Silva P. "The Chemical Logic Behind Gluconeogenesis". Archived from the original on August 26, 2009. Retrieved September 8, 2009.
^Cite error: The named reference Beitz2004 was invoked but never defined (see the help page).
^Kaleta C, de Figueiredo LF, Werner S, Guthke R, Ristow M, Schuster S (July 2011). "In silico evidence for gluconeogenesis from fatty acids in humans". PLOS Computational Biology. 7 (7): e1002116. Bibcode:2011PLSCB...7E2116K. doi:10.1371/journal.pcbi.1002116. PMC 3140964. PMID 21814506.
^Swe MT, Pongchaidecha A, Chatsudthipong V, Chattipakorn N, Lungkaphin A (June 2019). "Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions". Journal of Cellular Physiology. 234 (6): 8134–8151. doi:10.1002/jcp.27598. PMID 30370538. S2CID 53097552.
^Rodwell V (2015). Harper's illustrated Biochemistry, 30th edition. USA: McGraw Hill. p. 193. ISBN 978-0-07-182537-5.
fatty acids to glucose. Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes...
fatty acids to glucose. Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes...
other half of the Cori cycle. In the liver, gluconeogenesis occurs. From an intuitive perspective, gluconeogenesis reverses both glycolysis and fermentation...
intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty...
|alt=Glycolysis and Gluconeogenesis edit]] The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534". Pyruvate decarboxylation...
is an enzyme in the lyase family used in the metabolic pathway of gluconeogenesis. It converts oxaloacetate into phosphoenolpyruvate and carbon dioxide...
enzyme for gluconeogenesis, a biochemical pathway in which the liver generates glucose from pyruvate and other substrates. Gluconeogenesis utilizes noncarbohydrate...
breakdown of muscle protein in order to use amino acids as substrates for gluconeogenesis, the breakdown of fat in adipose tissue to fatty acids, and oxidative...
|alt=Glycolysis and Gluconeogenesis edit]] The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534". Some of the metabolites...
|alt=Glycolysis and Gluconeogenesis edit]] The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534". PEP may be used...
acid) is an amino acid that can be converted into glucose through gluconeogenesis. This is in contrast to the ketogenic amino acids, which are converted...
disorders. The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually...
with the glycerol being turned into glucose in the liver via the gluconeogenesis pathway. When even the glucose made from glycerol reserves start declining...
and adrenaline are then released to stimulate glycogenolysis and gluconeogenesis in the liver, in addition to lipolysis in adipose tissue. As glycogen...
providing a substrate for gluconeogenesis. Its impact is complex and diverse. In general, cortisol stimulates gluconeogenesis (the synthesis of 'new' glucose...
concentrations of glucose in the blood. Metabolic effects: Stimulation of gluconeogenesis, in particular, in the liver: This pathway results in the synthesis...
glucose by gluconeogenesis. Glucagon turns off glycolysis in the liver, causing glycolytic intermediates to be shuttled to gluconeogenesis. Glucagon also...
traditionally a catabolic hormone, but also stimulates the anabolic process of gluconeogenesis by the liver, and to a lesser extent the kidney cortex and intestines...
bacteria, plants, and animals. In mammals, PC plays a crucial role in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitters, and in glucose-induced...
specific. It is used as a source of energy for protein synthesis and gluconeogenesis. GTP is essential to signal transduction, in particular with G-proteins...
and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. L-Alanine is produced industrially by decarboxylation...
and is instead used to produce glucose via gluconeogenesis. This utilization of oxaloacetate in gluconeogenesis can make it unavailable to condense with...
of gluconeogenesis and glycogenolysis. FOXO1 also activates transcription of phosphoenolpyruvate carboxykinase, which is required for gluconeogenesis. The...
Phosphatases can also act on carbohydrates, such as intermediates in gluconeogenesis. Gluconeogenesis is a biosynthetic pathway wherein glucose is created from noncarbohydrate...
neurotransmitters. Glucagon functions to signal the liver to begin gluconeogenesis which increases glucose levels in the blood. Glucagon will bind to...
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