Editing Citric acid cycle (section)

== Steps ==
There are ten basic steps in the citric acid cycle, as outlined below. The cycle is continuously supplied with new carbon in the form of [[acetyl-CoA]], entering at step 0 in the table.<ref name=Biochemistryofplants/>
{| class="wikitable"
!
!Reaction type
!Substrates
!Enzyme
!Products
!Comment
|-
|{{nowrap|0 / 10}}
|[[Aldol condensation]]
|[[Oxaloacetic acid|Oxaloacetate]] + [[Acetyl CoA]] + H<sub>2</sub>O
|[[Citrate synthase]]
|[[Citric acid|Citrate]] + [[Coenzyme A|CoA-SH]]
|irreversible, extends the 4C [[Oxaloacetic acid|oxaloacetate]] to a 6C molecule
|-
|1
| [[Dehydration reaction|Dehydration]]
|[[Citrate]]
| rowspan="2" | [[Aconitase]]
|''[[Cis–trans isomerism|cis]]''-[[Aconitic acid|Aconitate]] + H<sub>2</sub>O
|rowspan=2|reversible [[Isomerization|isomerisation]]
|-
|2
|[[Hydration reaction|Hydration]]
|[[Aconitate|''cis''-Aconitate]] + H<sub>2</sub>O
|[[Isocitric acid|Isocitrate]]
|-
|3
|[[Oxidation]]
|[[Isocitrate]] + [[Nicotinamide adenine dinucleotide|NAD]]<sup>+</sup>
| rowspan="2" | [[Isocitrate dehydrogenase]]
|[[Oxalosuccinic acid|Oxalosuccinate]] + [[Nicotinamide adenine dinucleotide|NADH + H <sup>+</sup>]]
|generates [[NADH]] (equivalent of 2.5 ATP)
|-
|4
|[[Decarboxylation]]
|[[Oxalosuccinate]]
|[[alpha-Ketoglutaric acid|α-Ketoglutarate]] + CO<sub>2</sub>
|rate-limiting, irreversible stage, generates a 5C molecule
|-
|5
|Oxidative<br />[[decarboxylation]]
|[[alpha-Ketoglutaric acid|α-Ketoglutarate]] + NAD<sup>+</sup> + CoA-SH
|[[Alpha-ketoglutarate dehydrogenase|α-Ketoglutarate<br />dehydrogenase]], [[Thiamine pyrophosphate]], [[Lipoic acid]], Mg++,transsuccinytase
|[[Succinyl-CoA]] + [[Nicotinamide adenine dinucleotide|NADH + H <sup>+</sup>]] + CO<sub>2</sub>
|irreversible stage, generates [[Nicotinamide adenine dinucleotide|NADH]] (equivalent of 2.5 ATP), regenerates the 4C chain (CoA excluded)
|-
|6
|[[Substrate-level phosphorylation|Substrate-level<br />phosphorylation]]
|[[Succinyl-CoA]] + [[Guanosine diphosphate|GDP]] + [[Inorganic phosphate|P<sub>i</sub>]]
|[[Succinyl coenzyme A synthetase|Succinyl-CoA synthetase]]
|[[Succinic acid|Succinate]] + CoA-SH + [[Guanosine triphosphate|GTP]]
|or [[adenosine diphosphate|ADP]]→[[adenosine triphosphate|ATP]] instead of GDP→GTP,<ref name="Stryer"/> generates 1 ATP or equivalent.<br />[[Condensation reaction]] of [[Guanosine diphosphate|GDP]] + [[Inorganic phosphate|P<sub>i</sub>]] and [[hydrolysis]] of [[succinyl-CoA]] involve the H<sub>2</sub>O needed for balanced equation.
|-
|7
|[[Redox|Oxidation]]
|[[Succinate]] + [[ubiquinone]] (Q)
|[[Succinate dehydrogenase]]
|[[Fumaric acid|Fumarate]] + [[ubiquinol]] (QH<sub>2</sub>)
|uses [[Flavin adenine dinucleotide|FAD]] as a [[prosthetic group]] (FAD→FADH<sub>2</sub> in the first step of the reaction) in the enzyme.<ref name="Stryer"/><br />These two electrons are later transferred to QH<sub>2</sub> during Complex II of the ETC, where they generate the equivalent of 1.5 ATP
|-
|8
|[[Hydration reaction|Hydration]]
|[[Fumarate]] + H<sub>2</sub>O
|[[Fumarase]]
|''L''-[[Malic acid|Malate]]
|Hydration of C-C double bond
|-
|9
|[[Redox|Oxidation]]
|[[Malate|<small>L</small>-Malate]] + NAD<sup>+</sup>
|[[Malate dehydrogenase]]
|[[Oxaloacetate]] + NADH + H<sup>+</sup>
|reversible (in fact, equilibrium favors malate), generates [[NADH]] (equivalent of 2.5 ATP)
|-
|10 / 0
|[[Aldol condensation]]
|[[Oxaloacetic acid|Oxaloacetate]] + [[Acetyl CoA]] + H<sub>2</sub>O
|[[Citrate synthase]]
|[[Citric acid|Citrate]] + [[Coenzyme A|CoA-SH]]
|This is the same as step 0 and restarts the cycle. The reaction is irreversible and extends the 4C oxaloacetate to a 6C molecule
|}

Two [[carbon]] atoms are [[oxidation|oxidized]] to [[carbon dioxide|CO<sub>2</sub>]], the energy from these reactions is transferred to other metabolic processes through [[Guanosine triphosphate|GTP]] (or ATP), and as electrons in [[NADH]] and [[Ubiquinol|QH<sub>2</sub>]]. The NADH generated in the citric acid cycle may later be oxidized (donate its electrons) to drive [[ATP synthase|ATP synthesis]] in a type of process called [[oxidative phosphorylation]].<ref name="Voet_2004" /> [[Flavin adenine dinucleotide|FADH<sub>2</sub>]] is covalently attached to [[succinate dehydrogenase]], an enzyme which functions both in the citric acid cycle and the mitochondrial [[electron transport chain]] in oxidative phosphorylation. FADH<sub>2</sub>, therefore, facilitates transfer of electrons to [[coenzyme Q]], which is the final electron acceptor of the reaction catalyzed by the succinate:ubiquinone oxidoreductase complex, also acting as an intermediate in the [[electron transport chain]].<ref name="Stryer">{{cite book|vauthors=Stryer L, Berg J, Tymoczko JL|title=Biochemistry|publisher=W. H. Freeman|location=San Francisco|year=2002|isbn=978-0-7167-4684-3}}</ref>

Mitochondria in animals, including humans, possess two [[succinyl-CoA]] synthetases: one that produces GTP from GDP, and another that produces ATP from ADP.<ref name="pmid9765291">{{cite journal|vauthors=Johnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO|title=Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes|journal=The Journal of Biological Chemistry|volume=273|issue=42|pages=27580–6|date=October 1998|pmid=9765291|doi=10.1074/jbc.273.42.27580|doi-access=free}}</ref> Plants have the type that produces ATP (ADP-forming succinyl-CoA synthetase).<ref name=Biochemistryofplants>{{cite book|vauthors=Jones RC, Buchanan BB, Gruissem W|title=Biochemistry & molecular biology of plants|edition=1st|publisher=American Society of Plant Physiologists|location=Rockville, Md|year=2000|isbn=978-0-943088-39-6|url=https://archive.org/details/biochemistrymole00buch}}</ref> Several of the enzymes in the cycle may be loosely associated in a multienzyme [[protein complex]] within the [[mitochondrial matrix]].<ref name="pmid3086126">{{cite journal|vauthors=Barnes SJ, Weitzman PD|title=Organization of citric acid cycle enzymes into a multienzyme cluster|journal=FEBS Letters|volume=201|issue=2|pages=267–70|date=June 1986|pmid=3086126|doi=10.1016/0014-5793(86)80621-4|doi-access=free|bibcode=1986FEBSL.201..267B|s2cid=43052163}}</ref>

The GTP that is formed by GDP-forming succinyl-CoA synthetase may be utilized by [[nucleoside-diphosphate kinase]] to form ATP (the catalyzed reaction is GTP + ADP → GDP + ATP).<ref name="Stryer"/>

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