Glycolytic Pathway

Abstract

Glycolysis converts glucose into two molecule of the three‐carbon compound pyruvate with the production of two ATPs. Glycolysis provides metabolic intermediates needed for the synthesis of macromolecules, ATP needed to drive energy‐requiring processes and pyruvate needed to complete the oxidation of glucose to carbon dioxide and water. Cells that lack mitochondria (e.g. red blood cells) are completely dependent on glycolysis for ATP. Cells containing mitochondria use glycolysis as a preparatory pathway for the complete oxidation of glucose to carbon dioxide with the production of larger amounts of ATP. Glycolysis produces ATP in emergency situations, for example, when hypoxia prevents ATP production by mitochondria. Oxygen normally suppresses glycolysis because mitochondria maintain ATP at levels that inhibit regulatory enzymes of the pathway (Pasteur effect). Lack of inhibition of glycolysis by oxygen in cancer cells (Warburg effect) is a phenomenon of great interest. Recent studies show that the Warburg effect promotes rapid growth of tumours by providing precursors for macromolecule synthesis.

Key Concepts

  • Glycolysis refers to a metabolic pathway by which organisms extract energy in the form of ATP during the conversion of glucose into pyruvate and lactate.
  • Glycolysis produces ATP required for energy‐requiring reactions and processes, for example, ion transport, protein synthesis and reactions catalysed by kinases.
  • Anaerobic glycolysis (glycolysis in the absence of oxygen) converts the six‐carbon compound glucose into two molecules of the three‐carbon compound lactate with the production of two molecules of ATP.
  • When oxygen is present, glycolysis produces two molecules of the three‐carbon compound pyruvate which can be used for the synthesis of other molecules or oxidised completely to carbon dioxide and water by the citric acid cycle.
  • The presence of oxygen suppresses the rate of glycolysis in normal cells because most of the ATP is provided by oxidative phosphorylation (Pasteur effect).
  • Lack of inhibition of glycolysis by oxygen in cancer cells (Warburg effect) is of great interest as a possible therapeutic target.
  • The Warburg effect maintains high concentrations of metabolic intermediates needed for rapid growth of tumours.
  • Phosphorylation of glucose sets up the molecule for splitting into three‐carbon fragments that undergo an oxidation reaction that traps energy by substrate‐level phosphorylation.
  • Glycolysis is controlled by the properties of three regulatory enzymes: hexokinase, phosphofructokinase 1 and pyruvate kinase.
  • Glycolysis is subject to feedback inhibition by its end product ATP at the levels of phosphofructokinase‐1 and pyruvate kinase.

Keywords: glycolysis; fermentation; glucose; ATP; Pasteur effect; Warburg effect; mitochondria; phosphofructokinase; lactate

Figure 1. Glucose is a major fuel of cellular metabolism. ADP, adenosine diphosphate; ATP, adenosine triphosphate; CAC, citric acid cycle; CoA, coenzyme A; GLUT, glucose transporter and NADH, reduced nicotinamide–adenine dinucleotide.
Figure 2. (a–c) Glycolysis in the absence of oxygen: net production of 2ATP per glucose. ADP, adenosine diphosphate; ATP, adenosine triphosphate and NADH, reduced nicotinamide–adenine dinucleotide.
Figure 3. Formation of lactic acid.
Figure 4. Flow of reducing equivalents via malate–aspartate shuttle system. α‐KG, α‐ketoglutarate; BPG, bisphosphoglycerate; FMN, flavin mononucleotide; G3P, glyceraldehyde 3‐phosphate; NADH, reduced nicotinamide–adenine dinucleotide and OAA, oxaloacetic acid. As glucose has six carbons and pyruvate three carbons, it takes 1/2 of a mole of glucose to make a mole of pyruvate.
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References

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Further Reading

Berg JM, Tymoczko JL and Stryer L (2010) Glycolysis and gluconeogenesis. Biochemistry, 7th edn, pp. 433–469. New York: WH Freeman.

Garrett RH and Grisham CM (2012) Glycolysis. Biochemistry, 5th edn, pp. 577–608. Fort Worth, TX: Saunders College Publishing.

Gibson DM and Harris RA (2002) Metabolic Regulation in Mammals. London: Taylor and Frances.

Harris RA (2011) Carbohydrate metabolism I. Major metabolic pathways and their control. Devlin TM, (ed). Textbook of Biochemistry with Clinical Corrections, 7th edn, pp. 591–646. New York: Wiley‐Liss.

Harris RA and Crabb DW (2011) Metabolic interrelationships. Devlin TM, (ed). Textbook of Biochemistry with Clinical Corrections, 7th edn, pp. 839–882. New York: Wiley‐Liss.

King MW (2014) themedicalbiochemistrypage.org

Nelson DL and Cox MM (2008) Glycolysis and the catabolism of hexoses. Lehninger Principles of Biochemistry, 5th edn, pp. 527–550. New York: Worth.

Newsholme EA and Leech AR (1983) Biochemistry for the Medical Sciences. New York: John Wiley and Sons, Inc.

Voet D and Voet JG (2010) Glycolysis. Biochemistry, 4th edn, pp. 593–637. New York: John Wiley and Sons, Inc.

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How to Cite close
Harris, Robert A, and Harper, Edwin T(Apr 2015) Glycolytic Pathway. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000619.pub3]