Editing High-energy phosphate (section)

==Description==
High-energy phosphate bonds are usually [[pyrophosphate]] bonds, acid [[anhydride]] linkages formed by taking [[phosphoric acid]] derivatives and dehydrating them. As a consequence, the [[hydrolysis]] of these bonds is [[exergonic reaction|exergonic]] under physiological conditions, releasing [[Gibbs free energy]].{{cn|date=December 2024}}

{| class="wikitable floatright"
|+"High energy" phosphate reactions
|-
! Reaction
|-
| ATP + H<sub>2</sub>O → ADP + P<sub>i</sub>  
|-
| ADP + H<sub>2</sub>O → [[Adenosine monophosphate|AMP]] + P<sub>i</sub>  
|-
| ATP + H<sub>2</sub>O → AMP + PP<sub>i</sub> 
|-
| PP<sub>i</sub> + H<sub>2</sub>O → 2 P<sub>i</sub>  
|-
|}

Except for PP<sub>i</sub> → 2 P<sub>i</sub>, these reactions are, in general, not allowed to go uncontrolled in the human cell but are instead coupled to other processes needing energy to drive them to completion. Thus, high-energy phosphate reactions can:{{cn|date=December 2024}}
* provide energy to cellular processes, allowing them to run
* couple processes to a particular nucleoside, allowing for regulatory control of the process
* drive a reaction out of equilibrium (drive it ''to the right'') by promoting one direction of the reaction faster than the equilibrium can relax.

The one exception is of value because it allows a single hydrolysis, ATP + H<sub>2</sub>O → AMP + PP<sub>i</sub>, to effectively supply the energy of hydrolysis of two high-energy bonds, with the hydrolysis of PP<sub>i</sub> being allowed to go to completion in a separate reaction.  The AMP is regenerated to ATP in two steps, with the equilibrium reaction ATP + AMP ↔ 2ADP, followed by regeneration of ATP by the usual means, [[oxidative phosphorylation]] or other energy-producing pathways such as [[glycolysis]].{{cn|date=December 2024}}

Often, high-energy phosphate bonds are denoted by the character '~'. In this "squiggle" notation, ATP becomes A-P~P~P. The squiggle notation was invented by [[Fritz Albert Lipmann]], who first proposed ATP as the main energy transfer molecule of the cell, in 1941.<ref>{{cite journal |author=Lipmann F |title= Metabolic generation and utilization of phosphate bond energy |journal=Adv. Enzymol. |volume=1 |pages=99–162 |year=1941 |issn=0196-7398}}</ref> Lipmann's notation emphasizes the special nature of these bonds.<ref name=Stryer>Lubert Stryer ''Biochemistry'', 3rd edition, 1988. Chapter 13, p. 318</ref> Stryer states: {{blockquote|text=ATP is often called a high energy compound and its phosphoanhydride bonds are referred to as high-energy bonds. There is nothing special about the bonds themselves. ''They are high-energy bonds in the sense that free energy is released when they are hydrolyzed'', for the reasons given above.  Lipmann’s term "high-energy bond" and his symbol ~P (squiggle P) for a compound having a high phosphate group transfer potential are vivid, concise, and useful notations. In fact Lipmann's squiggle did much to stimulate interest in bioenergetics.<ref name=Stryer/>}}

The term 'high energy' with respect to these bonds can be misleading because the negative free energy change is not due directly to the breaking of the bonds themselves. The breaking of these bonds, like the breaking of most bonds, is [[endergonic]] and consumes energy rather than releasing it. The negative [[thermodynamic free energy|free energy]] change comes instead from the fact that the bonds formed after hydrolysis - or the [[phosphorylation]] of a residue by ATP - are lower in energy than the bonds present before hydrolysis. (This includes ''all'' of the bonds involved in the reaction, not just the phosphate bonds themselves). This effect is due to a number of factors including increased [[resonance stabilization]] and [[solvation]] of the products relative to the reactants, and destabilization of the reactants due to electrostatic repulsion between neighboring phosphorus atoms.<ref>{{cite book |last1=Garrett |first1=Reginald H. |last2=Grisham |first2=Charles M. |edition=6th |date=2016 |title=Biochemistry |publisher=Cengage Learning |page=64 |isbn=978-1305577206}}</ref>