Substrate - level phosphorylation - Wikipedia Substrate - level phosphorylation hide This article has multiple issues. Please help improve it or discuss these issues on the talk page. ( Learn how and when to remove these template messages ) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. ( November 2012 ) This article may be confusing or unclear to readers. Please help us clarify the article. There might be a discussion about this on the talk page. ( November 2009 ) Substrate - level phosphorylation exemplified with the conversion of ADP to ATP Substrate - level phosphorylation is a metabolic reaction that results in the formation of ATP or GTP by the direct transfer of a phosphoryl ( PO ) group to ADP or GDP from another phosphorylated compound. Unlike oxidative phosphorylation, oxidation and phosphorylation are not coupled in the process of substrate - level phosphorylation, and reactive intermediates are most often gained in the course of oxidation processes in catabolism. Most ATP is generated by oxidative phosphorylation in aerobic or anaerobic respiration while substrate - level phosphorylation provides a quicker, less efficient source of ATP, independent of external electron acceptors. This is the case in human erythrocytes, which have no mitochondria, and in oxygen - depleted muscle. Contents 1 Overview 2 Glycolysis 3 Mitochondria 3.1 Phosphoenolpyruvate carboxykinase 3.2 Succinate - CoA ligase 3.3 Monofunctional C1 - tetrahydrofolate synthase 4 Other mechanisms 5 Importance of substrate - level phosphorylation in anoxia 6 Oxidative phosphorylation 7 References Overview Substrate - level phosphorylation occurs in the cytoplasm of cells during glycolysis and in mitochondria either during the Krebs cycle or by MTHFD1L ( EC 6.3. 4.3 ), an enzyme interconverting ADP + phosphate + 10 - formyltetrahydrofolate to ATP + formate + tetrahydrofolate ( reversibly ), under both aerobic and anaerobic conditions. In the pay - off phase of glycolysis, a net of 2 ATP are produced by substrate - level phosphorylation. Glycolysis Main article : Glycolysis The first substrate - level phosphorylation occurs after the conversion of 3 - phosphoglyceraldehyde and Pi and NAD+ to 1, 3 - bisphosphoglycerate via glyceraldehyde 3 - phosphate dehydrogenase. 1, 3 - bisphosphoglycerate is then dephosphorylated via phosphoglycerate kinase, producing 3 - phosphoglycerate and ATP through a substrate - level phosphorylation. The second substrate - level phosphorylation occurs by dephosphorylating phosphoenolpyruvate, catalyzed by pyruvate kinase, producing pyruvate and ATP. During the preparatory phase, each 6 - carbon glucose molecule is broken into two 3 - carbon molecules. Thus, in glycolysis dephosphorylation results in the production of 4 ATP. However, the prior preparatory phase consumes 2 ATP, so the net yield in glycolysis is 2 ATP. 2 molecules of NADH are also produced and can be used in oxidative phosphorylation to generate more ATP. Mitochondria ATP can be generated by substrate - level phosphorylation in mitochondria in a pathway that is independent from the proton motive force. In the matrix there are three reactions capable of substrate - level phosphorylation, utilizing either phosphoenolpyruvate carboxykinase or succinate - CoA ligase, or monofunctional C1 - tetrahydrofolate synthase. Phosphoenolpyruvate carboxykinase Mitochondrial phosphoenolpyruvate carboxykinase is thought to participate in the transfer of the phosphorylation potential from the matrix to the cytosol and vice versa.. However, it is strongly favored towards GTP hydrolysis, thus it is not really considered as an important source of intra-mitochondrial substrate - level phosphorylation. Succinate - CoA ligase Succinate - CoA ligase is a heterodimer composed of an invariant α - subunit and a substrate - specific ß - subunit, encoded by either SUCLA2 or SUCLG2. This combination results in either an ADP - forming succinate - CoA ligase ( A-SUCL, EC 6.2. 1.5 ) or a GDP - forming succinate - CoA ligase ( G - SUCL, EC 6.2. 1.4 ). The ADP - forming succinate - CoA ligase is potentially the only matrix enzyme generating ATP in the absence of a proton motive force, capable of maintaining matrix ATP levels under energy - limited conditions, such as transient hypoxia. Monofunctional C1 - tetrahydrofolate synthase This enzyme is encoded by MTHFD1L and reversibly interconverts ADP + phosphate + 10 - formyltetrahydrofolate to ATP + formate + tetrahydrofolate. Other mechanisms In working skeletal muscles and the brain, Phosphocreatine is stored as a readily available high - energy phosphate supply, and the enzyme creatine phosphokinase transfers a phosphate from phosphocreatine to ADP to produce ATP. Then the ATP releases giving chemical energy. This is sometimes erroneously considered to be substrate - level phosphorylation, although it is a transphosphorylation. Importance of substrate - level phosphorylation in anoxia During anoxia, provision of ATP by substrate - level phosphorylation in the matrix is important not only as a mere means of energy, but also to prevent mitochondria from straining glycolytic ATP reserves by maintaining the adenine nucleotide translocator in ' forward mode ' carrying ATP towards the cytosol,,. Oxidative phosphorylation Main article : Oxidative phosphorylation An alternative method used to create ATP is through oxidative phosphorylation, which takes place during cellular respiration. This process utilizes the oxidation of NADH to NAD, yielding 3 ATP, and of FADH to FAD, yielding 2 ATP. The potential energy stored as an electrochemical gradient of protons ( H ) across the inner mitochondrial membrane is required to generate ATP from ADP and P ( inorganic phosphate molecule ), a key difference from substrate - level phosphorylation. This gradient is exploited by ATP synthase acting as a pore, allowing H from the mitochondrial intermembrane space to move down its electrochemical gradient into the matrix and coupling the release of free energy to ATP synthesis. Conversely, electron transfer provides the energy required to actively pump H out of the matrix. References Jump up ^ Lambeth DO, Tews KN, Adkins S, Frohlich D, Milavetz BI ( 2004 ). `` Expression of two succinyl - CoA synthetases with different nucleotide specificities in mammalian tissues ''. The Journal of Biological Chemistry. 279 ( 35 ) : 36621 -- 4. doi : 10.1074 / jbc. M406884200. PMID 15234968. Jump up ^ Ottaway JH, McClellan JA, Saunderson CL ( 1981 ). `` Succinic thiokinase and metabolic control ''. The International Journal of Biochemistry. 13 ( 4 ) : 401 -- 10. doi : 10.1016 / 0020 - 711x ( 81 ) 90111 - 7. PMID 6263728. Jump up ^ Lambeth DO ( 2002 ). `` What is the function of GTP produced in the Krebs citric acid cycle ? ''. IUBMB Life. 54 ( 3 ) : 143 -- 4. doi : 10.1080 / 15216540214539. PMID 12489642. Jump up ^ Wilson DF, Erecińska M, Schramm VL ( 1983 ). `` Evaluation of the relationship between the intra - and extramitochondrial ATP / ADP ratios using phosphoenolpyruvate carboxykinase ''. The Journal of Biological Chemistry. 258 ( 17 ) : 10464 -- 73. PMID 6885788. Jump up ^ Johnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO ( 1998 ). `` Genetic evidence for the expression of ATP - and GTP - specific succinyl - CoA synthetases in multicellular eucaryotes ''. The Journal of Biological Chemistry. 273 ( 42 ) : 27580 -- 6. doi : 10.1074 / jbc. 273.42. 27580. PMID 9765291. Jump up ^ Forward operation of adenine nucleotide translocase during F0F1 - ATPase reversal : critical role of matrix substrate - level phosphorylation. Chinopoulos C, Gerencser AA, Mandi M, Mathe K, Töröcsik B, Doczi J, Turiak L, Kiss G, Konràd C, Vajda S, Vereczki V, Oh RJ, Adam - Vizi V. FASEB J. 2010 Jul ; 24 ( 7 ) : 2405 - 16. doi : 10.1096 / fj. 09 - 149898. PMID : 20207940 Jump up ^ Mitochondrial consumption of cytosolic ATP : not so fast. Chinopoulos C. FEBS Lett. 2011 May 6 ; 585 ( 9 ) : 1255 - 9. doi : 10.1016 / j. febslet. 2011.04. 004. PMID : 21486564 Jump up ^ The `` B space '' of mitochondrial phosphorylation. Chinopoulos C. J Neurosci Res. 2011 Dec ; 89 ( 12 ) : 1897 - 904. doi : 10.1002 / jnr. 22659. PMID : 21541983 Molecular and cellular biology portal Metabolism portal Retrieved from `` https://en.wikipedia.org/w/index.php?title=Substrate-level_phosphorylation&oldid=862541413 '' Categories : Metabolism Phosphorus Hidden categories : Articles needing additional references from November 2012 All articles needing additional references Wikipedia articles needing clarification from November 2009 All Wikipedia articles needing clarification Articles with multiple maintenance issues Talk Contents About Wikipedia Deutsch Ελληνικά Español Français Galego 한국어 Italiano 日本 語 Română Русский Suomi Türkçe Українська 粵語 中文 6 more Edit links This page was last edited on 5 October 2018, at 02 : 05 ( UTC ). Text is available under the Creative Commons Attribution - ShareAlike License ; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia ® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization. About Wikipedia

Question: where does the most substrate level phosphorylation occur
Answer: in the cytoplasm of  cells