Editing Adenosine triphosphate (section)

====Citric acid cycle====
{{Main|Citric acid cycle|Oxidative phosphorylation}}

In the [[mitochondrion]], pyruvate is oxidized by the [[pyruvate dehydrogenase complex]] to the [[acetyl]] group, which is fully oxidized to carbon dioxide by the [[citric acid cycle]] (also known as the [[Hans Krebs (biochemist)|Krebs]] cycle). Every "turn" of the citric acid cycle produces two molecules of carbon dioxide, one equivalent of ATP [[guanosine triphosphate]] (GTP) through [[substrate-level phosphorylation]] catalyzed by [[succinyl-CoA synthetase]], as succinyl-CoA is converted to succinate, three equivalents of NADH, and one equivalent of [[Flavin group|FADH<sub>2</sub>]]. NADH and FADH<sub>2</sub> are recycled (to NAD<sup>+</sup> and [[Flavin adenine dinucleotide|FAD]], respectively) by [[oxidative phosphorylation]], generating additional ATP. The oxidation of NADH results in the synthesis of 2–3 equivalents of ATP, and the oxidation of one FADH<sub>2</sub> yields between 1–2 equivalents of ATP.<ref name="Rich" /> The majority of cellular ATP is generated by this process. Although the citric acid cycle itself does not involve molecular [[oxygen]], it is an obligately [[aerobic glycolysis|aerobic]] process because O<sub>2</sub> is used to recycle the NADH and FADH<sub>2</sub>. In the absence of oxygen, the citric acid cycle ceases.<ref name="Lodish" />

The generation of ATP by the mitochondrion from cytosolic NADH relies on the [[malate-aspartate shuttle]] (and to a lesser extent, the [[glycerol-phosphate shuttle]]) because the inner mitochondrial membrane is impermeable to NADH and NAD<sup>+</sup>. Instead of transferring the generated NADH, a [[malate dehydrogenase]] enzyme converts [[oxaloacetate]] to [[malate]], which is translocated to the mitochondrial matrix. Another malate dehydrogenase-catalyzed reaction occurs in the opposite direction, producing oxaloacetate and NADH from the newly transported malate and the mitochondrion's interior store of NAD<sup>+</sup>. A [[transaminase]] converts the oxaloacetate to [[aspartate]] for transport back across the membrane and into the intermembrane space.<ref name="Lodish" /><!--will put the antiporter/full cycle in the shuttle article-->

In oxidative phosphorylation, the passage of electrons from NADH and FADH<sub>2</sub> through the electron transport chain releases the energy to pump [[proton]]s out of the mitochondrial matrix and into the intermembrane space. This pumping generates a [[proton motive force]] that is the net effect of a pH gradient and an [[electric potential]] gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient&nbsp;– that is, from the intermembrane space to the matrix&nbsp;– yields ATP by ATP synthase.<ref>{{cite journal |last1=Abrahams |first1=J. |last2=Leslie |first2=A. |last3=Lutter |first3=R. |last4=Walker |first4=J. | title = Structure at 2.8&nbsp;Å resolution of F1-ATPase from bovine heart mitochondria | journal = Nature | volume = 370 | issue = 6491 | pages = 621–628 | year = 1994 |pmid=8065448 | doi = 10.1038/370621a0 |bibcode=1994Natur.370..621A |s2cid=4275221 }}</ref> Three ATP are produced per turn.

Although oxygen consumption appears fundamental for the maintenance of the proton motive force, in the event of oxygen shortage ([[Hypoxia (medical)|hypoxia]]), intracellular acidosis (mediated by enhanced glycolytic rates and [[ATP hydrolysis]]), contributes to mitochondrial membrane potential and directly drives ATP synthesis.<ref>{{cite journal | pmid = 30713504 | volume=9, 1914 | title=Acidosis Maintains the Function of Brain Mitochondria in Hypoxia-Tolerant Triplefin Fish: A Strategy to Survive Acute Hypoxic Exposure? | pmc=6346031 | date=January 2019 | journal=Front Physiol | doi=10.3389/fphys.2018.01941 | last1 = Devaux | first1 = JBL | last2 = Hedges | first2 = CP | last3 = Hickey | first3 = AJR| page=1941 | doi-access=free }}</ref>

Most of the ATP synthesized in the mitochondria will be used for cellular processes in the cytosol; thus it must be exported from its site of synthesis in the mitochondrial matrix. ATP outward movement is favored by the membrane's electrochemical potential because the cytosol has a relatively positive charge compared to the relatively negative matrix. For every ATP transported out, it costs 1 H<sup>+</sup>. Producing one ATP costs about 3  H<sup>+</sup>. Therefore, making and exporting one ATP requires  4H<sup>+.</sup> The inner membrane contains an [[antiporter]], the ADP/ATP translocase, which is an [[integral membrane protein]] used to exchange newly synthesized ATP in the matrix for ADP in the intermembrane space.<ref name="Brandolin">{{cite journal |last1=Dahout-Gonzalez |first1=C. |last2=Nury |first2=H. |last3=Trézéguet |first3=V. |last4=Lauquin |first4=G. |last5=Pebay-Peyroula |first5=E. |last6=Brandolin |first6=G. | title = Molecular, functional, and pathological aspects of the mitochondrial ADP/ATP carrier | journal = Physiology | volume = 21 | pages = 242–249 | year = 2006| pmid = 16868313 | doi=10.1152/physiol.00005.2006 | issue = 4 }}</ref>

=====Regulation=====
The citric acid cycle is regulated mainly by the availability of key substrates, particularly the ratio of NAD<sup>+</sup> to NADH and the concentrations of [[calcium]], inorganic phosphate, ATP, ADP, and AMP. [[Citrate]]&nbsp;– the ion that gives its name to the cycle&nbsp;– is a feedback inhibitor of [[citrate synthase]] and also inhibits PFK, providing a direct link between the regulation of the citric acid cycle and glycolysis.<ref name="Voet" /> {{confusing|date=October 2024}}