The Chemical Biology of Phosphorus
Chapter 6: Activated Phosphoryl Groups and Biosynthetic Paths to ATP
Published:29 Oct 2020
Special Collection: 2020 ebook collectionSeries: Chemical Biology
The Chemical Biology of Phosphorus, The Royal Society of Chemistry, 2020, ch. 6, pp. 177-203.
Download citation file:
One manifestation that ATP is the major phosphoryl group cellular energy currency, driving hundreds of coupled equilibria in cells, is the observation that organisms make and utilize their body weights in ATP every day. For a 70 kg adult human that is about a 1000-fold turnover of the steady state inventory of 70–75 grams of bodily ATP. Organisms generate ATP by two major metabolic routes. One route involves enzymatic processing of glucose by the glycolytic pathway, generating the acyl phosphate 1,3-diphosphoglycerate and then phosphoenolpyruvate as sequential metabolites. Both those molecules are thermodynamically activated but kinetically stable enough to undergo enzymatic transfer of a –PO32− group to ADP to form ATP. However, by far the major flux (>90%) to ATP arises in eukaryotes by flow of metabolically derived electrons (e.g. 24 e− from glucose oxidation to 6 CO2) through a series of redox intermediates for ultimate four-electron reduction of O2+4 protons to 2H2O. Those four protons arise from anisotropic transmembrane proton pumping of protons from mitochondrial matrix to inner membrane space as the electrons tumble down potential drops of >1 volt. The mitochondrial transmembrane ATP synthase allows the protons to flow back down their concentration gradient to drive otherwise unfavorable coupling of inorganic phosphate and ADP to create the phosphoric P–O–P side chain linkage in ATP.