Fate of Pyruvate & TCA cycle

what’s the different fate for pyruvate?

• Anaerobic glycolysis - no mitochondria / O₂

  • need to regenerate NAD⁺ by using NADH to make lactate to keep glycolysis going, uses up H⁺

  • lactate can accumulate → acidosis

• Aerobic metabolism - mitochondria & O₂ available

  • pyruvate enters mitochondria & oxidized in TCA cycle

  • producing CO₂ & H₂O while consuming H⁺

  • generate energy in ETC

What is the structure for mitochondria membrane?

Double-membraned

• outer membrane - freely permeable

• inner membrane - impermeable, has specificity using transporters

• inter-membrane space - where all enzymes are

what’s the structure of PDC?

• my multiple copies of 3 enzymatic subunits: E1, E2, E3

• requires 5 cofactors for catalysis, found in mitochondria matrix

  • TPP, Lipoamide, FAD, CoA, NAD+

What’s the role of CO₂ in PDC reaction?

• resulted from redox decarboxylation

• drives reaction forward because it doesn’t dissolve → immediately leaves

How is PDC reaction regulated?

Feedback Inhibition:

• Acetyl-CoA inhibits E2

• NADH inhibits E3

  • turns off process, causing pyruvate build up & glycolysis off

PTM:

• phosphorylation onto E1

• PD Kinase - turn PDC OFF

  • add P, using ATP

  • when ⬆energy (ATP, NADH, Acetyl-CoA)

• PD Phosphatase - turn PDC ON

  • remove P by hydrolysis

  • when ⬇energy (ADP, NAD⁺, Ca²⁺)

How is PDC reaction regulated @ muscle at rest?
- how is PD Kinase regulated?

• rest = ⬆energy state (lots Acetyl-CoA, NADH, ATP)

• turns PDC off by feedback inhibition & phosphorylation by PD Kinase

  • PD Kinase activated by ⬆NADH & Acetyl-CoA

How is PDC reaction regulated @ muscle at exercise?
- how is PD Phosphatase regulated?

when exercising, ⬆intracellular Ca²⁺ & ⬇energy state

• causes ⬆ADP, pyruvate (∵active glycolysis) → need more energy

  • ⬆ADP, pyruvate inhibits PD Kinase

• turns PDC ON → PD Phosphatase

  • PD Phosphatase is:

    • activated by Ca²⁺

Summarize the allosteric control of PDC

Acetyl-CoA, NADH, pyruvate, ADP, Ca²⁺

why is Acetyl-CoA important? What is its structure?

• it’s central to generating energy from any dietary source

what’s the structure of oxaloacetate & citrate?

what’s the enzyme linking TCA & ETC?

• location?

• how does it work?

succinate dehydrogenase

• embedded in inner mitochondrial membrane

• in TCA:

  • dehydrogenation of succinate → fumarate

  • succinate lose 2H+, transferring 2e- to FAD

  • producing FADH₂

• in ETC:

  • FADH2 bound to SDH, transfer e^- to coenzyme Q

How is TCA cycle regulated by?

Stimulated by:

• ADP, Ca²⁺ (⬇energy & muscle use)

  • Ca²⁺ activates dehydrogenase, generating NADH/FADH

Inhibited by:

• citrate (product inhibition), NADH, ATP

*NADH is the main energy sensor of mitochondria

• ⬆NADH = stop TCA / ⬇NADH = start TCA

what’s the source of Acetyl-CoA for TCA cycle?

sugars, fatty acids, amino acids