Editing Pyruvate dehydrogenase complex (section)

==Regulation==
Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: [[Adenosine triphosphate|ATP]]/[[Adenosine diphosphate|ADP]], [[NADH]]/NAD<sup>+</sup> and [[acetyl-CoA]]/[[Coenzyme A|CoA]].{{Citation needed|date=December 2023}}

In eukaryotes PDC is tightly regulated by its own specific [[Pyruvate dehydrogenase kinase]] (PDK) and [[Pyruvate dehydrogenase phosphatase]] (PDP), deactivating and activating it respectively.<ref name=":1">{{Citation|last=Pelley|first=John W.|title=6 - Glycolysis and Pyruvate Oxidation|date=2012-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780323074469000064|work=Elsevier's Integrated Review Biochemistry (Second Edition)|pages=49–55|editor-last=Pelley|editor-first=John W.|place=Philadelphia|publisher=W.B. Saunders|language=en|doi=10.1016/b978-0-323-07446-9.00006-4|isbn=978-0-323-07446-9|access-date=2020-11-16|url-access=subscription}}</ref> 
* PDK [[Phosphorylation|phosphorylates]] three specific [[serine]] residues on E1 with different affinities. Phosphorylation of any one of them (using [[Adenosine triphosphate|ATP]]) renders E1 (and in consequence the entire complex) inactive.<ref name=":1" />
* [[Dephosphorylation]] of E1 by PDP reinstates complex activity.<ref name=":1" />

Products of the reaction act as [[Allosteric regulation|allosteric inhibitors]] of the PDC, because they activate PDK. Substrates in turn inhibit PDK, reactivating PDC.

During [[starvation]], PDK increases in amount in most tissues, including [[skeletal muscle]], via increased [[Transcription (biology)|gene transcription]]. Under the same conditions, the amount of PDP decreases. The resulting inhibition of PDC prevents muscle and other tissues from catabolizing glucose and [[gluconeogenesis]] precursors. Metabolism shifts toward [[Lipid metabolism|fat utilization]], while muscle protein breakdown to supply gluconeogenesis precursors is minimized, and available glucose is spared for use by the [[brain]].{{Citation needed|date=December 2023}}

[[Calcium]] ions have a role in regulation of PDC in muscle tissue, because it activates PDP, stimulating [[glycolysis]] on its release into the cytosol - during [[muscle contraction]]. Some products of these transcriptions release H2 into the muscles. This can cause calcium ions to decay over time.{{Citation needed|date=December 2023}}