Klappa13.3 - PDH
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- FrontPyruvate dehydrogenase (PDH) functionBackLinks glycolysis to the TCA cycle by converting pyruvate to acetyl-CoA
- FrontKey PDH reactionBackPyruvate → acetyl-CoA
- FrontLocation of PDH reactionBackMitochondrial matrix
- FrontRole of PDH in metabolismBackBridge between glycolysis in the cytosol and the TCA cycle in mitochondria
- FrontImportance of PDH for glucose oxidationBackWithout PDH, glucose cannot be fully oxidized
- FrontOverall PDH reactionBackPyruvate + NAD⁺ + CoA → acetyl-CoA + NADH + CO₂
- FrontDecarboxylation in PDH reactionBackRemoval of CO₂ from pyruvate
- FrontCarbon change in PDH reactionBackPyruvate loses one carbon as CO₂
- FrontOxidation in PDH reactionBackNAD⁺ is reduced to NADH
- FrontAddition of CoA in PDH reactionBackForms acetyl-CoA
- FrontReversibility of PDH reactionBackIrreversible
- FrontMetabolic consequence of PDH irreversibilityBackAcetyl-CoA cannot be converted back to glucose
- FrontCommitment step of PDHBackPyruvate conversion to acetyl-CoA commits carbon to energy production
- FrontPDH enzyme structureBackPDH is a multi-enzyme complex
- FrontDefinition of multi-enzyme complexBackA group of enzymes working together in sequence
- FrontAdvantages of multi-enzyme complexesBackFaster reactions, prevention of intermediate loss, and efficient transfer between steps
- FrontNumber of enzyme components in PDHBackThree enzyme components
- FrontE1 enzymeBackPyruvate dehydrogenase
- FrontFunction of E1BackRemoves CO₂ from pyruvate
- FrontE2 enzymeBackDihydrolipoyl transacetylase
- FrontFunction of E2BackTransfers acetyl group to CoA
- FrontE3 enzymeBackDihydrolipoyl dehydrogenase
- FrontFunction of E3BackRegenerates oxidized cofactors
- FrontSequential action of PDH enzymesBackEach enzyme performs one step in sequence
- FrontNumber of PDH cofactorsBackFive cofactors
- FrontFive cofactors of PDHBackTPP, lipoic acid, CoA, FAD, and NAD⁺
- FrontTPPBackThiamine pyrophosphate
- FrontRole of TPP in PDHBackRequired for decarboxylation
- FrontLipoic acid role in PDHBackTransfers the acetyl group between enzyme components
- FrontCoenzyme A role in PDHBackCarries the acetyl group as acetyl-CoA
- FrontFAD role in PDHBackAccepts electrons during the reaction
- FrontNAD⁺ role in PDHBackAccepts electrons to form NADH
- FrontTightly bound cofactors in PDHBackTPP, lipoic acid, and FAD
- FrontLoosely bound cofactors in PDHBackCoA and NAD⁺
- FrontVitamin associated with TPPBackThiamine (vitamin B1)
- FrontClinical relevance of thiamine deficiencyBackImpairs PDH function
- FrontStepwise PDH mechanism overviewBackPyruvate loses CO₂, the 2-carbon unit binds lipoic acid, transfers to CoA forming acetyl-CoA, and electrons are transferred to NADH
- FrontCarbon flow in PDHBackCarbon from pyruvate becomes acetyl-CoA
- FrontElectron flow in PDHBackElectrons are transferred to NADH
- FrontMain regulatory mechanisms of PDHBackCovalent modification and allosteric regulation
- FrontCovalent regulation of PDHBackPhosphorylation and dephosphorylation control activity
- FrontPDH kinaseBackEnzyme that phosphorylates PDH and inactivates it
- FrontEffect of PDH kinaseBackPDH becomes inactive when phosphorylated
- FrontPDH phosphataseBackEnzyme that removes phosphate and activates PDH
- FrontEffect of PDH phosphataseBackPDH becomes active when dephosphorylated
- FrontKey rule of PDH regulationBackPhosphorylation turns PDH off and dephosphorylation turns it on
- FrontAllosteric inhibitors of PDHBackATP, NADH, and acetyl-CoA
- FrontEffect of inhibitors on PDHBackDecrease PDH activity
- FrontAllosteric activators of PDHBackADP and pyruvate
- FrontEffect of activators on PDHBackIncrease PDH activity
- FrontEnergy status control of PDHBackHigh energy inhibits PDH and low energy activates PDH
- FrontPhysiologic condition when PDH is activeBackWhen energy is needed and glucose oxidation is required
- FrontPhysiologic condition when PDH is inactiveBackWhen energy and acetyl-CoA levels are already high
- FrontMetabolic decision controlled by PDHBackDetermines whether pyruvate enters the TCA cycle
- FrontEffect of PDH dysfunction on pyruvate metabolismBackPyruvate is converted to lactate instead of acetyl-CoA
- FrontResult of PDH deficiencyBackIncreased lactate and decreased energy production
- FrontReason lactate increases in PDH deficiencyBackPyruvate cannot be converted to acetyl-CoA and is diverted to lactate
- FrontImportance of PDH for aerobic metabolismBackEssential for aerobic ATP production
- FrontCore PDH reaction summaryBackPyruvate → acetyl-CoA + CO₂ + NADH
- FrontLocation summary of PDHBackMitochondrial matrix
- FrontIrreversibility summary of PDHBackPyruvate cannot return to glucose after conversion to acetyl-CoA
- FrontPDH enzyme summaryBackE1 performs decarboxylation, E2 transfers acetyl group, and E3 transfers electrons
- FrontPDH cofactors summaryBackTPP, lipoic acid, CoA, FAD, and NAD⁺
- FrontPDH regulation OFF stateBackPhosphorylated form with high ATP, NADH, and acetyl-CoA
- FrontPDH regulation ON stateBackDephosphorylated form with high ADP and pyruvate
- FrontBig function of PDHBackLinks glycolysis to the TCA cycle
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