Substrate-level phosphorylation is defined as the production of ATP or GTP following the transfer of a phosphate group from a substrate to ADP or GDP.[1]
The energy released from the cleavage of a high-energy bond of the substrate facilitates the formation of the phosphoanhydride bond.[2] Part of this energy drives the reaction toward nucleotide triphosphate formation, while another part is stored in the newly formed bond.[3]
This process involves soluble enzymes and chemical intermediates, differing from oxidative phosphorylation and photophosphorylation, which rely on membrane-bound enzymes and transmembrane proton gradients.[2]
Examples of substrate-level phosphorylation are found in the glycolytic pathway and the citric acid cycle.[3]
Although under aerobic conditions most ATP is produced by oxidative phosphorylation and by photophosphorylation in photosynthetic organisms, substrate-level phosphorylation remains essential in energy metabolism, particularly under anaerobic conditions.[4][5]
Contents
Glycolysis and ADP phosphorylation
Two well-known examples of substrate-level phosphorylation occur in glycolysis.
During the energy recovery phase of glycolysis, two of the five reactions directly extract and store chemical energy from glucose as ATP.[5]
These reactions are catalyzed by phosphoglycerate kinase (EC 2.7.2.3) and pyruvate kinase (EC 2.7.1.40).
In these reactions, a high-energy phosphate group is transferred to ADP from:
- 1,3-bisphosphoglycerate, producing one molecule of ATP and one molecule of 3-phosphoglycerate;
- phosphoenolpyruvate, producing one molecule of ATP and one molecule of pyruvate.[6]
These two glycolytic substrate-level phosphorylation reactions enable ATP synthesis even under anaerobic conditions.[3]
The citric acid cycle and GDP phosphorylation
Another example of substrate-level phosphorylation occurs in the citric acid cycle in the reaction catalyzed by succinyl-CoA synthetase, also known as succinate-CoA ligase (EC 6.2.1.4). This enzyme catalyzes the cleavage of the high-energy thioester bond in succinyl-CoA, similar to that in acetyl-CoA. The energy released drives the formation of a phosphoanhydride bond, leading to the conversion of GDP to GTP.[5]
References
- ^ Ha C.E., Bhagavan N.V.. Chapter 11 – Carbohydrate metabolism I: glycolysis and the tricarboxylic acid cycle. Editor(s): Chung Eun Ha, N.V. Bhagavan. Essentials of Medical Biochemistry. 3rd Edition. Academic Press, 2023, pages 203-227. doi:10.1016/B978-0-323-88541-6.00030-2
- ^ a b Garrett R.H., Grisham C.M. Biochemistry. 4th Edition. Brooks/Cole, Cengage Learning, 2010.
- ^ a b c Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 6th Edition. W.H. Freeman and Company, 2012.
- ^ Michal G., Schomburg D. Biochemical pathways. An atlas of biochemistry and molecular biology. 2nd Edition. John Wiley J. & Sons, Inc. 2012.
- ^ a b c Voet D. and Voet J.D. Biochemistry. 4th Edition. John Wiley J. & Sons, Inc. 2011.
- ^ Moran L.A., Horton H.R., Scrimgeour K.G., Perry M.D. Principles of Biochemistry. 5th Edition. Pearson, 2012.