Editing Mitochondrion (section)

====Pyruvate and the citric acid cycle====
{{Main|Citric acid cycle}}

[[Pyruvate]] molecules produced by [[glycolysis]] are [[active transport|actively transported]] across the inner mitochondrial membrane, and into the matrix where they can either be [[Redox|oxidized]] and combined with [[coenzyme A]] to form CO{{sub|2}}, [[acetyl-CoA]], and [[NADH]],<ref name="Voet-2006" /> or they can be [[carboxylated]] (by [[pyruvate carboxylase]]) to form oxaloacetate. This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle and is therefore an [[anaplerotic reaction]], increasing the cycle's capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g., in [[striated muscle tissue|muscle]]) are suddenly increased by activity.<ref name="Stryer-1995">{{cite book | vauthors = Stryer L | title=In: Biochemistry. |chapter= Citric acid cycle. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 509–527, 569–579, 614–616, 638–641, 732–735, 739–748, 770–773 |isbn= 0716720094 }}</ref>

In the citric acid cycle, all the intermediates (e.g. [[citrate]], [[Isocitric acid|iso-citrate]], [[Alpha-Ketoglutaric acid|alpha-ketoglutarate]], succinate, [[Fumaric acid|fumarate]], [[Malic acid|malate]] and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an [[Anaplerotic reactions|anaplerotic]] effect, and its removal has a cataplerotic effect. These anaplerotic and [[cataplerotic]] reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases the rate of [[Adenosine triphosphate|ATP]] production by the mitochondrion, and thus the availability of ATP to the cell.<ref name="Stryer-1995" />

Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the [[beta-oxidation]] of [[fatty acids]], is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO{{sub|2}} and water, with the energy thus released captured in the form of ATP.<ref name="Stryer-1995" />

In the liver, the [[carboxylation]] of [[cytosol]]ic pyruvate into intra-mitochondrial oxaloacetate is an early step in the [[gluconeogenesis|gluconeogenic]] pathway, which converts [[lactic acid|lactate]] and de-aminated [[alanine]] into glucose,<ref name="Voet-2006" /><ref name="Stryer-1995" /> under the influence of high levels of [[glucagon]] and/or [[epinephrine]] in the blood.<ref name="Stryer-1995" /> Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted to cytosolic oxaloacetate, and ultimately to glucose, in a process that is almost the reverse of [[glycolysis]].<ref name="Stryer-1995" />

The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of [[succinate dehydrogenase]], which is bound to the inner mitochondrial membrane as part of Complex II.<ref>{{cite journal | vauthors = King A, Selak MA, Gottlieb E | title = Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer | journal = Oncogene | volume = 25 | issue = 34 | pages = 4675–4682 | date = August 2006 | pmid = 16892081 | doi = 10.1038/sj.onc.1209594 | doi-access =  }}</ref> The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of [[NADH]] and one molecule of [[FADH2|FADH{{sub|2}}]]) that are a source of electrons for the [[electron transport chain]], and a molecule of [[Guanosine triphosphate|GTP]] (which is readily converted to an ATP).<ref name="Voet-2006"/>