Fate of Pyruvate & TCA cycle

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13 Terms

1
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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

2
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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

3
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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+

<ul><li><p>my multiple copies of <strong>3 enzymatic subunits: E1, E2, E3</strong></p></li><li><p>requires <strong>5 cofactors</strong> for catalysis, found in mitochondria matrix </p><ul><li><p>TPP, Lipoamide, FAD, CoA, NAD+</p></li></ul></li></ul><p></p>
4
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What’s the role of CO2 in PDC reaction?

  • resulted from redox decarboxylation

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

<ul><li><p>resulted from redox decarboxylation</p></li><li><p>drives reaction forward because it doesn’t dissolve → immediately leaves </p></li></ul><p></p>
5
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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+)

<p>Feedback Inhibition:</p><ul><li><p>Acetyl-CoA inhibits <strong>E2</strong></p></li><li><p>NADH inhibits <strong>E3</strong></p><ul><li><p>turns off process, causing pyruvate build up &amp; glycolysis off</p></li></ul></li></ul><p>PTM:</p><ul><li><p><strong>phosphorylation</strong> onto<strong> E1</strong></p></li><li><p><strong>PD Kinase</strong> - turn PDC OFF</p><ul><li><p>add P, using ATP </p></li><li><p>when <span data-name="arrow_up" data-type="emoji">⬆</span>energy (ATP, NADH, Acetyl-CoA)</p></li></ul></li><li><p><strong>PD Phosphatase </strong>- turn PDC ON</p><ul><li><p>remove P by hydrolysis</p></li><li><p>when <span data-name="arrow_down" data-type="emoji">⬇</span>energy (ADP, NAD<sup>+</sup>, Ca<sup>2+</sup>)</p></li></ul></li></ul><p></p>
6
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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

<ul><li><p>rest = <span data-name="arrow_up" data-type="emoji">⬆</span>energy state (lots Acetyl-CoA, NADH, ATP)</p></li><li><p>turns PDC off by feedback inhibition &amp; phosphorylation by PD Kinase</p><ul><li><p>PD Kinase activated by <span data-name="arrow_up" data-type="emoji">⬆</span>NADH &amp; Acetyl-CoA</p></li></ul></li></ul><p></p>
7
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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+

<p>when exercising, <span data-name="arrow_up" data-type="emoji">⬆</span>intracellular Ca<sup>2+ </sup>&amp; <span data-name="arrow_down" data-type="emoji">⬇</span>energy state </p><ul><li><p>causes <span data-name="arrow_up" data-type="emoji">⬆</span>ADP, pyruvate (∵active glycolysis) → need more energy</p><ul><li><p> <span data-name="arrow_up" data-type="emoji">⬆</span>ADP, pyruvate inhibits PD Kinase</p></li></ul></li><li><p>turns PDC ON → PD Phosphatase</p><ul><li><p>PD Phosphatase is:</p><ul><li><p>activated by Ca<sup>2+</sup></p></li></ul></li></ul></li></ul><p></p>
8
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Summarize the allosteric control of PDC

Acetyl-CoA, NADH, pyruvate, ADP, Ca2+

<p>Acetyl-CoA, NADH, pyruvate, ADP, Ca<sup>2+</sup></p>
9
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why is Acetyl-CoA important? What is its structure?

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

<ul><li><p>it’s central to generating energy from any dietary source</p></li></ul><p></p>
10
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what’s the structure of oxaloacetate & citrate?

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11
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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

<p><strong>succinate dehydrogenase</strong></p><ul><li><p>embedded in <strong>inner mitochondrial membrane </strong></p></li><li><p>in TCA:</p><ul><li><p>dehydrogenation of succinate → fumarate</p></li><li><p>succinate lose 2H+, transferring 2e- to FAD</p></li><li><p><u>producing FADH<sub>2</sub></u></p></li></ul></li><li><p>in ETC:</p><ul><li><p>FADH2 bound to SDH, transfer e<sup>-</sup> to <u>coenzyme Q</u></p></li></ul></li></ul><p></p>
12
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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

<p><span style="color: rgb(0, 161, 27);">Stimulated</span> by:</p><ul><li><p>ADP, Ca<sup>2+</sup> (<span data-name="arrow_down" data-type="emoji">⬇</span>energy &amp; muscle use)</p><ul><li><p>Ca<sup>2+</sup> activates dehydrogenase, generating NADH/FADH</p></li></ul></li></ul><p><span style="color: rgb(255, 0, 0);">Inhibited</span> by:</p><ul><li><p>citrate (product inhibition), NADH, ATP</p></li></ul><p>*NADH is the main energy sensor of mitochondria</p><ul><li><p><span data-name="arrow_up" data-type="emoji">⬆</span>NADH = stop TCA / <span data-name="arrow_down" data-type="emoji">⬇</span>NADH = start TCA</p></li></ul><p></p>
13
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what’s the source of Acetyl-CoA for TCA cycle?

sugars, fatty acids, amino acids