[Music] pyruvate dehydrogenase complex the pdh complex also known as the pyruvate dehydrogenase complex is a multi-enzyme complex present on the inner mitochondrial membrane the molecular weight of the pdh complex is 9 into 10 to the power of 6 pyruvate is produced in the cytosol as the end product of aerobic glycolysis it enters mitochondria by a pyruvate protons import which is present in the inner mitochondrial membrane in the mitochondrial matrix pyruvate is oxidatively decarboxylated to form acetyl coenzyme a the oxidation of pyruvate to acetyl coenzyme a is an irreversible reaction this is the link reaction between glycolysis and the citric acid cycle the overall reaction of pdh complex is as follows the pdh complex consists of 3 enzymes and 5 coenzymes the 3 enzymes are pyruvate dehydrogenase with TPP as a coenzyme dihydrolipoyl transacetylase dihydrolipoyl dehydrogenase the 5 coenzymes are thymine pyrophosphate or vitamin b1 fa d or vitamin b2 nad or vitamin b3 coenzyme a or vitamin b5 and lipoic acid sequence of reactions of the ph complex is described in the following steps firstly pyruvate dehydrogenase with TPP as coenzyme d carboxylates pyruvate - hydroxy ethyl thiamine pyrophosphate then dihydrolipoyl transacetylase catalyzes conversion hydroxi e-file thiamine pyrophosphate into asset i'll lipoamide and then transfers the acetyl group to coenzyme a to produce acetyl coenzyme a now dihydrolipoyl dehydrogenase catalyzes conversion of reduced Lipa mind into oxidized lipo mind by transferring the reduced equivalence of fa d and this completes the cycle fadh2 in turn transfers the reducing equivalents to nad plus to give NADH + H+ this NADH + H+ enters a respiratory chain to give 2.5 ATP by oxidative phosphorylation as a whole five ATP are released in the PD H complex and from two moles of para weight which is formed from glucose by glycolysis all these intermediates of PTH catalyzed reaction are not free but bound with an enzyme complex together called as the PD H complex a comparable enzyme with PTH is alpha ketoglutarate dehydrogenase complex of the citric acid cycle which catalyzes the oxidative decarboxylation of alpha ketoglutarate into succinylcholine dime a regulation of PAH regulation of the pyruvate dehydrogenase complex is mainly an example of end product inhibition it is also regulated by phosphorylation and dephosphorylation PTH is active as d phospho enzyme which means indeed phosphorylated state while it is inactive as phospho enzyme that is phosphorylated state PTH phosphatase which is responsible to maintain PTH complex an active state is promoted by calcium-magnesium and mainly insulin so insulin activates PTH complex PTH kinase which are responsible for the inactive PTH is promoted by ATP nadh and acetyl coenzyme a while it is inhibited by nad plus coenzyme a and pyruvate net result is that in the presence of high-energy molecules like ATP nadh the pyruvate dehydrogenase complex is turned off because when enough amount of ATP is already present there is no need for the pyruvate dehydrogenase complex to continue clinical application arsenic poisoning arsenide binds to dial which is a self hydral group of lipoic acid and makes it unavailable to serve as a cofactor by this way in arsenic poisoning enzymes of the pyruvate dehydrogenase complex and alpha ketoglutarate complex are inhibited by arsenic inherited are acquired alcoholics deficiency of PD H causes lactic acidosis due to rapid conversion of accumulated pyruvate into lactic acid point to be noted here is pyruvate is derived from carbohydrates an acetyl coenzyme a mainly from fats which are triglycerides fatty acids cholesterol carbohydrates in excess can form fats but fats can never be converted to carbohydrates because linked reaction is irreversible an exception to this rule is go Cyril and proprio neck acid which are derived from fats but they can be converted to glucose