Pyruvate Dehydrogenase (PDH) Complex

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14 Terms

1
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Pyruvate

synthesized via glycolysis and transported to mitochondrial matrix by the mitochondrial pyruvate carrier (MPC)

<p>synthesized via glycolysis and transported to mitochondrial matrix by the mitochondrial pyruvate carrier (MPC)</p>
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Conversion of Pyruvate to Acetyl CoA

in the mitochondrial matrix, pyruvate is decarboxylated by the pyruvate dehydrogenase complex to form acetyl coA

<p>in the mitochondrial matrix, pyruvate is decarboxylated by the pyruvate dehydrogenase complex to form acetyl coA</p>
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Components of PDH

  • E1: Pyruvate Dehydrogenase

  • E2: Dihydrolipoyl Transacetylase

  • E3: Dihydrolipoyl Dehydrogenase

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Decarboxylation Mechanism

  • goal: converts pyruvate to hydroxyethyl-TPP (loss of CO2)

  • enzyme: pyruvate dehydrogenase (E1)

  • prosthetic: thiamine pyrophosphate (TPP)

<ul><li><p>goal: converts pyruvate to hydroxyethyl-TPP (loss of CO2)</p></li><li><p>enzyme: pyruvate dehydrogenase (E1)</p></li><li><p>prosthetic: thiamine pyrophosphate (TPP) </p></li></ul>
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Oxidation Mechanism

  • goal: converts hydroxyethyl-TPP to acetyllipoamide

  • enzyme: pyruvate dehydrogenase (E1)

  • prosthetic group: Lipoamide (a component of E2)

<ul><li><p>goal: converts hydroxyethyl-TPP to acetyllipoamide</p></li><li><p>enzyme: pyruvate dehydrogenase (E1)</p></li><li><p>prosthetic group: Lipoamide (a component of E2)</p></li></ul>
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Transfer Mechanism

  • goal: transfers acetyl group from acetyl lipoamide to coenzyme A (CoA)

  • enzyme: dihydrolipoyl transacetylase (E2)

  • prosthetic group: coenzyme A

<ul><li><p>goal: transfers acetyl group from acetyl lipoamide to coenzyme A (CoA)</p></li><li><p>enzyme: dihydrolipoyl transacetylase (E2)</p></li><li><p>prosthetic group: coenzyme A</p></li></ul>
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“Reset” Mechanism

  • goal: oxidation of dihydrolipoamide to lipoamide

  • enzyme: dihydrolipoyl dehydrogenase (E3)

  • prosthetic group: FAD/NAD+

<ul><li><p>goal: oxidation of dihydrolipoamide to lipoamide</p></li><li><p>enzyme: dihydrolipoyl dehydrogenase (E3)</p></li><li><p>prosthetic group: FAD/NAD+</p></li></ul>
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NAD+

  • can get reduced to NADH

  • oxidizing agent

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FAD

  • can get reduced to FADH2

  • oxidizing agent

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Structure of PDH (144 subunits)

  • eight E2 trimers (three subunits each → 24 subunits total)

  • each E2 trimer is surrounded by an E1 trimer (12×8 = 96 subunits total)

  • core of eight E2 trimers are surrounded by 12 E3 (aB → 24 subunits)

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Functional Domains of E2 Trimer

  • lipoamide binding domain

  • E3 interaction domain

  • transacetylase domain

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Beriberi

neurological condition that results from a deficiency in thiamine (vitamin B1), a precursor of TPP

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Arsenite Poisoning

inhibits the PDH complex by (reversibly) inactivating the dihydrolipoamide component of E2

<p>inhibits the PDH complex by (reversibly) inactivating the dihydrolipoamide component of E2</p>
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Acetyl CoA

main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production

<p> main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production</p>