Editing Citric acid cycle (section)

== Overview ==
{{More citations needed|section|date=August 2022}}
[[File:Acetyl-CoA-2D_colored.svg|thumb|upright=1.6|class=skin-invert-image|Structural diagram of acetyl-CoA: The portion in blue, on the left, is the [[Acetyl|acetyl group]]; the portion in black is [[coenzyme A]].]]
The citric acid cycle is a [[metabolic pathway]] that connects [[carbohydrate]], [[fat]], and [[protein]] [[metabolism]]. The [[Chemical reaction|reaction]]s of the cycle are carried out by eight [[enzymes]] that completely oxidize [[acetate]] (a two carbon molecule), in the form of acetyl-CoA, into two molecules each of carbon dioxide and water. Through [[catabolism]] of sugars, fats, and proteins, the two-carbon organic product acetyl-CoA is produced which enters the citric acid cycle. The reactions of the cycle also convert three equivalents of [[nicotinamide adenine dinucleotide]] (NAD<sup>+</sup>) into three equivalents of reduced [[Nicotinamide adenine dinucleotide|NAD]] (NADH), one equivalent of [[flavin adenine dinucleotide]] (FAD) into one equivalent of [[Flavin adenine dinucleotide|FADH<sub>2</sub>]], and one equivalent each of [[guanosine diphosphate]] (GDP) and inorganic [[phosphate]] (P<sub>i</sub>) into one equivalent of [[guanosine triphosphate]] (GTP). The NADH and FADH<sub>2</sub> generated by the citric acid cycle are, in turn, used by the [[oxidative phosphorylation]] pathway to generate energy-rich ATP.

One of the primary sources of acetyl-CoA is from the breakdown of sugars by [[glycolysis]] which yield [[pyruvic acid|pyruvate]] that in turn is decarboxylated by the [[pyruvate dehydrogenase complex]] generating acetyl-CoA according to the following reaction scheme:

{{block indent|{{underset|pyruvate|2=CH<sub>3</sub>C(=O)C(=O)O<sup>−</sup>}} + [[Coenzyme A|HSCoA]] + NAD<sup>+</sup> → {{underset|acetyl-CoA|2=CH<sub>3</sub>C(=O)SCoA}} + NADH + CO<sub>2</sub>}}

The product of this reaction, acetyl-CoA, is the starting point for the citric acid cycle. [[Acetyl-CoA carboxylase|Acetyl-CoA]] may also be obtained from the oxidation of [[fatty acid]]s. Below is a schematic outline of the cycle:
* The [[citric acid]] cycle begins with the transfer of a two-carbon [[acetyl]] group from acetyl-CoA to the four-carbon acceptor compound (oxaloacetate) to form a six-carbon compound (citrate).
* The citrate then goes through a series of chemical transformations, losing two [[carboxyl]] groups as [[Carbon dioxide|CO<sub>2</sub>]]. The carbons lost as CO<sub>2</sub> originate from what was oxaloacetate, not directly from acetyl-CoA. The carbons donated by acetyl-CoA become part of the oxaloacetate carbon backbone after the first turn of the citric acid cycle. Loss of the acetyl-CoA-donated carbons as CO<sub>2</sub> requires several turns of the citric acid cycle. However, because of the role of the citric acid cycle in [[anabolic|anabolism]], they might not be lost, since many citric acid cycle intermediates are also used as precursors for the [[biosynthesis]] of other molecules.<ref name="pmid2106256">{{cite journal|vauthors=Wolfe RR, Jahoor F|title=Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: implications for tracer studies of substrate oxidation|journal=The American Journal of Clinical Nutrition|volume=51|issue=2|pages=248–52|date=February 1990|pmid=2106256|doi=10.1093/ajcn/51.2.248|doi-access=free}}</ref>
* Most of the electrons made available by the oxidative steps of the cycle are transferred to NAD<sup>+</sup>, forming NADH. For each acetyl group that enters the citric acid cycle, three molecules of NADH are produced. The citric acid cycle includes a series of redox reactions in mitochondria.{{Clarify|date=September 2019}}<ref>{{Cite book|vauthors=Berg JM, Tymoczko JL, Stryer L|date=2002|chapter=The Citric Acid Cycle|url=https://www.ncbi.nlm.nih.gov/books/NBK21163/|title=Biochemistry|edition=5th|isbn=0-7167-3051-0|publisher=W H Freeman}}</ref>
* In addition, electrons from the succinate oxidation step are transferred first to the FAD cofactor of succinate dehydrogenase, reducing it to FADH<sub>2</sub>, and eventually to [[ubiquinone]] (Q) in the [[Mitochondrion|mitochondrial membrane]], reducing it to [[ubiquinol]] (QH<sub>2</sub>) which is a substrate of the [[Electron transport chain|electron transfer chain]] at the level of [[Complex III]].
* For every NADH and FADH<sub>2</sub> that are produced in the citric acid cycle, 2.5 and 1.5 ATP molecules are generated in oxidative [[phosphorylation]], respectively.
* At the end of each cycle, the four-carbon [[Oxaloacetic acid|oxaloacetate]] has been regenerated, and the cycle continues.