Pyruvate dehydrogenase complex

pyruvate dehydrogenasemitochondrial pyruvate dehydrogenase complexPDCpyruvate dehydrogenase.pyruvate metabolism
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation.wikipedia
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Oxoglutarate dehydrogenase complex

α-ketoglutarate dehydrogenaseoxoglutarate dehydrogenasealpha-ketoglutarate dehydrogenase
This multi-enzyme complex is related structurally and functionally to the oxoglutarate dehydrogenase and branched-chain oxo-acid dehydrogenase multi-enzyme complexes.
Much like pyruvate dehydrogenase complex (PDC), this enzyme forms a complex composed of three components:

Citric acid cycle

Krebs cycleTCA cycletricarboxylic acid cycle
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.
One of the primary sources of acetyl-CoA is from the breakdown of sugars by glycolysis which yield pyruvate that in turn is decarboxylated by the pyruvate dehydrogenase complex generating acetyl-CoA according to the following reaction scheme:

Dihydrolipoyl transacetylase

dihydrolipoyllysine-residue acetyltransferaseDLATdihydrolipoamide acetyltransferase
At this point, the lipoate-thioester functionality is translocated into the dihydrolipoyl transacetylase (E2) active site, where a transacylation reaction transfers the acetyl from the "swinging arm" of lipoyl to the thiol of coenzyme A.
Dihydrolipoyl transacetylase (or dihydrolipoamide acetyltransferase) is an enzyme component of the multienzyme pyruvate dehydrogenase complex.

Acetyl-CoA

acetyl CoAacetyl coenzyme Aacetyl-coenzyme A
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD + and acetyl-CoA/CoA.
It is catalyzed by the pyruvate dehydrogenase complex.

Flavin adenine dinucleotide

FADFADH 2 FADH2
First, FAD oxidizes dihydrolipoate back to its lipoate resting state, producing FADH 2.
There are many flavoproteins besides components of the succinate dehydrogenase complex, including α-ketoglutarate dehydrogenase and a component of the pyruvate dehydrogenase complex; some examples are shown in section 6.

Lipoic acid

Alpha lipoic acidlipoatealpha-lipoic acid
The dihydrolipoate, still bound to a lysine residue of the complex, then migrates to the dihydrolipoyl dehydrogenase (E3) active site where it undergoes a flavin-mediated oxidation, identical in chemistry to disulfide isomerase.
One of the most studied roles of RLA is as a cofactor of the pyruvate dehydrogenase complex (PDC or PDHC), though it is a cofactor in other enzymatic systems as well (described below).

Pyruvate decarboxylation

oxidative decarboxylationpyruvate oxidationoxidative decarboxylation of pyruvate
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation.
Pyruvate decarboxylation or pyruvate oxidation, also known as link reaction, is the conversion of pyruvate into acetyl-CoA by the enzyme complex pyruvate dehydrogenase complex.

Cellular respiration

respirationaerobic respirationaerobic
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 is oxidized to acetyl-CoA and CO 2 by the pyruvate dehydrogenase complex (PDC).

Pyruvic acid

pyruvatepyruvate metabolismpyruvate metabolism, inborn errors
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Initially, pyruvate and thiamine pyrophosphate (TPP or vitamin B 1 ) are bound by pyruvate dehydrogenase subunits.
Pyruvate decarboxylation by the pyruvate dehydrogenase complex produces acetyl-CoA.

Pyruvate dehydrogenase kinase

(pyruvate dehydrogenase (acetyl-transferring)) kinaseEC 2.7.11.2Pyrubate dehydrogenase kinase
PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component.

E3 binding protein

E3
Eukaryotes also contain 12 copies of an additional core protein, E3 binding protein (E3BP).
The E3 binding protein is a component of the pyruvate dehydrogenase complex found only in eukaryotes.Defects in this gene are a cause of pyruvate dehydrogenase deficiency which results in neurological dysfunction and lactic acidosis in infancy and early childhood.

Adenosine triphosphate

ATPadenosine triphosphate (ATP)adenosine 5'-triphosphate
Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD + and acetyl-CoA/CoA.
In the mitochondrion, pyruvate is oxidized by the pyruvate dehydrogenase complex to the acetyl group, which is fully oxidized to carbon dioxide by the citric acid cycle (also known as the Krebs cycle).

Pyruvate dehydrogenase deficiency

pyruvate dehydrogenase complex deficiency diseaseDeficiency of pyruvate dehydrogenasepyruvate dehydrogenase (E1) deficiency
Pyruvate dehydrogenase deficiency can result from mutations in any of the enzymes or cofactors.
The pyruvate dehydrogenase complex (PDC) is a multi-enzyme complex that plays a vital role as a key regulatory step in the central pathways of energy metabolism in the mitochondria.

Enzyme

enzymologyenzymesenzymatic
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation.

Glycolysis

glycolyticglycolytic pathwayEmbden–Meyerhof pathway
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.

Metabolic pathway

metabolic pathwayspathwaypathways
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.

Branched-chain alpha-keto acid dehydrogenase complex

branched-chain alpha-keto acid dehydrogenasebranched-chain α-ketoacid dehydrogenase complex3-methyl-2-oxobutanoate dehydrogenase (lipoamide)
This multi-enzyme complex is related structurally and functionally to the oxoglutarate dehydrogenase and branched-chain oxo-acid dehydrogenase multi-enzyme complexes.

Pyruvate dehydrogenase

pyruvate dehydrogenase (lipoamide)Link reactionoxidation of pyruvate
Initially, pyruvate and thiamine pyrophosphate (TPP or vitamin B 1 ) are bound by pyruvate dehydrogenase subunits.
Pyruvate dehydrogenase is usually encountered as a component, referred to as E1, of the pyruvate dehydrogenase complex (PDC).

Coenzyme A

CoAco-enzyme Acoenzyme-A
At this point, the lipoate-thioester functionality is translocated into the dihydrolipoyl transacetylase (E2) active site, where a transacylation reaction transfers the acetyl from the "swinging arm" of lipoyl to the thiol of coenzyme A. Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD + and acetyl-CoA/CoA.

Dihydrolipoamide dehydrogenase

DLDdihydrolipoyl dehydrogenaselipoamide dehydrogenase
The dihydrolipoate, still bound to a lysine residue of the complex, then migrates to the dihydrolipoyl dehydrogenase (E3) active site where it undergoes a flavin-mediated oxidation, identical in chemistry to disulfide isomerase.

Thiamine

thiaminvitamin B 1 vitamin B1
Initially, pyruvate and thiamine pyrophosphate (TPP or vitamin B 1 ) are bound by pyruvate dehydrogenase subunits.

Thiazole

thiazolesthiazoliumthiazolium salt
The thiazolium ring of TPP is in a zwitterionic form, and the anionic C2 carbon performs a nucleophilic attack on the C2 (ketone) carbonyl of pyruvate.

Zwitterion

zwitterionicZwitterionsinner salt
The thiazolium ring of TPP is in a zwitterionic form, and the anionic C2 carbon performs a nucleophilic attack on the C2 (ketone) carbonyl of pyruvate.

Ion

cationanionions
The thiazolium ring of TPP is in a zwitterionic form, and the anionic C2 carbon performs a nucleophilic attack on the C2 (ketone) carbonyl of pyruvate.