Editing Pyruvate dehydrogenase complex (section)

{{Short description|Three-enzyme complex}}
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[[File:153-PyruvateDehydrogenaseComplex pyruvatedehydrogenase.tif|thumb|right| Pyruvate dehydrogenase complex]]

'''Pyruvate dehydrogenase complex''' ('''PDC''') is a complex of three [[enzyme]]s that converts [[pyruvate]] into [[acetyl-CoA]] by a process called [[pyruvate decarboxylation]].<ref name=":0">{{Citation|last1=DeBrosse|first1=Suzanne D.|title=Chapter 12 - Pyruvate Dehydrogenase Complex Deficiency|date=2016-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780128008775000127|work=Mitochondrial Case Studies|pages=93–101|editor-last=Saneto|editor-first=Russell P.|place=Boston|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-800877-5.00012-7|isbn=978-0-12-800877-5|access-date=2020-11-16|last2=Kerr|first2=Douglas S.|editor2-last=Parikh|editor2-first=Sumit|editor3-last=Cohen|editor3-first=Bruce H.|url-access=subscription}}</ref> Acetyl-CoA may then be used in the [[citric acid cycle]] to carry out [[cellular respiration]], and this complex links the [[glycolysis]] [[metabolic pathway]] to the [[citric acid cycle]]. Pyruvate decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it also involves the oxidation of pyruvate.<ref name=Berg>{{cite book|title=Biochemistry|author= J. M. Berg|author2= J. L. Tymoczko|author3=L. Stryer|publisher=Freeman|edition=6th|year=2007|isbn=978-0-7167-8724-2}}</ref>  The levels of pyruvate dehydrogenase enzymes play a major role in regulating the rate of [[carbohydrate metabolism]] and are strongly stimulated by the evolutionarily ancient hormone [[insulin]].  The PDC is opposed by the activity of [[pyruvate dehydrogenase kinase]], and this mechanism plays a pivotal role in regulating rates of carbohydrate and [[lipid metabolism]] in many physiological states across taxa, including feeding, starvation, [[diabetes mellitus]], [[hyperthyroidism]], and [[hibernation]].

The multi-enzyme complex is related structurally and functionally to the [[oxoglutarate dehydrogenase]] and [[Branched-chain alpha-keto acid dehydrogenase complex|branched-chain oxo-acid dehydrogenase multi-enzyme]] complexes.   A role for insulin in the regulation of glucose homeostasis, pyruvate dehydrogenase levels, and the generation of [[AMP-activated protein kinase]] (AMPK) in the [[electron transport chain]] has been evolutionarily conserved across species.  A shift in substrate utilization can be induced by conditions such as eating or fasting, and the oxidation of either glucose or fatty acids tends to suppress the use of the other substrate (a phenomenon known as the [[Randle cycle]]).  The intake of macronutrients stimulates the secretion and release of insulin and other chemical messengers such as [[glucagon-like peptide 1]] (GLP-1), which act to regulate glucose levels, [[insulin sensitivity]], satiety, and fat balance in the body.  In the postprandial period, insulin is produced by the [[pancreas]] and serves to activate carbohydrate metabolism and stimulate glucose disposal in order to meet metabolic demands and prevent [[glucotoxicity]].  When insulin is unable to efficiently stimulate glucose utilization, the body's tissues become resistant to its hypoglycemic effects, promoting the development of a state of [[insulin resistance]] over time.  This can happen because of chronic exposure to [[hyperinsulinemia]] due to poor diet, sedentary lifestyle, obesity, and other potentially modifiable [[risk factor]]s.  The phenomenon is similar to [[leptin resistance]] and can potentially lead to many deleterious health effects stemming from chronically elevated insulin levels, such as excessive fat storage and [[de novo synthesis]], hepatic and peripheral insulin resistance, [[nonalcoholic fatty liver disease]]] (NAFLD), [[hypertension]] and [[dyslipidemia]], and decreased [[resting energy expenditure]] (REE) caused by impaired [[specific dynamic action|diet-induced thermogenesis]].