BCH210H1 Lecture Notes - Lecture 28: Dihydrolipoamide Dehydrogenase, Pyruvate Dehydrogenase Complex, Pyruvate Dehydrogenase
25 May 2018
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Lecture 28: Mitochondrial Bioenergetics
Mitochondria
• Most reactions take place in the
inner membrane of
mitochondria
• Folds in the inner membrane
which increases surface area
PDC Equation
• ΔGº´ = - 33 kJ/mol
- Large negative (favorable) reaction
- CO2 release is energetically favorable
• Pyruvate dehydrogenase complex converts pyruvate to acetyl CoA
- Oxidative decarboxylation (lose C as CO2)
• Activates carbons for other reactions to take place (thiol-ester bond)
• Produce 1 CO2 and 1 NADH (in the mitochondria)
Pyruvate Dehydrogenase Complex
• E1 (pyruvate dehydrogenase) – take pyruvate and catalyze
decarboxylation and release of CO2 (has coenzyme that assists)
• E2 (dihydrolipoamide acetyltransferase) – acetyl group is transferred onto lipoamide (help catalyze this reaction
coenzyme) and coenzyme added on
• E3 (dihydrolipoamide dehydrogenase) – NADH is made (coenzyme FAD)
• Links the production of pyruvate in cytoplasm with citric acid cycle and ATP production in mitochondrial matrix
• Enzyme complex that carries out an oxidative decarboxylation reaction
• 5 cofactors are needed for catalysis – thiamine pyrophosphate (e1), lipoamide (e2), Coenzyme A (e2), FAD (E3),
NAD+ (E3) but only NADH is product
• Reaction produces CO2 (e1), acetyl CoA (e2), NADH (e3) + H+
• Reactions are highly favoured and irreversible (need a way to turn it off)
Control by feedback inhibition
• Acetyl CoA product by E2 increase → negative inhibition → E2
• NADH product by E3 increase → negative inhibition → E3
PDC covalent modification
• PDC active when dephosphorylated
• Auxiliary enzymes (PDK and PDP)
• E1 gets phosphorylated (first enzyme) to inhibit the process
• Allosteric regulation: muscle at rest → NADH and Acetyl CoA → activated
PD kinase → PDC to PDC-P (inactivate by phosphorylating E1)
• Muscle while running:
- Pyruvate/ADP negative inhibition on PD kinase (allosterically)
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Document Summary
Mitochondria: most reactions take place in the inner membrane of mitochondria, folds in the inner membrane which increases surface area. Pdc equation: g = - 33 kj/mol. Co2 release is energetically favorable: pyruvate dehydrogenase complex converts pyruvate to acetyl coa. Oxidative decarboxylation (lose c as co2: activates carbons for other reactions to take place (thiol-ester bond, produce 1 co2 and 1 nadh (in the mitochondria) Nad+ (e3) but only nadh is product: reaction produces co2 (e1), acetyl coa (e2), nadh (e3) + h, reactions are highly favoured and irreversible (need a way to turn it off) Control by feedback inhibition: acetyl coa product by e2 increase negative inhibition e2, nadh product by e3 increase negative inhibition e3. Pdc covalent modification: pdc active when dephosphorylated, auxiliary enzymes (pdk and pdp, e1 gets phosphorylated (first enzyme) to inhibit the process, allosteric regulation: muscle at rest nadh and acetyl coa activated. Pd kinase pdc to pdc-p (inactivate by phosphorylating e1: muscle while running:
