Ch 10 - Carb Metabolism

Question 1

Citric Acid Cycle

Answer 1

• aka Krebs cycle
• aka TCA cycle (tricarboxylic acid)
• oxidation of acetyl-CoA to CO2 and H2O
• Produce NADH and FADH2

Question 2

Make Acetyl-CoA

Answer 2

• pyruvate from glycolysis
  
  • pyruvate active transport into mitochondria
• pyruvate dehydrogenase complex - made of 5 enzymes
• pyruvate + CoA-SH + NAD+ = NADH + CO2 + AcetylCoA
• exergonic
• occurs in mitochondria
• Other sources:
  
  • beta oxidation - CoA-SH attached to fatty acid and removes 2 carbon chain
  • amino acid catabolism - lose amino group then become ketogenic, ketone bodies to acetyl-CoA
  • alcohol - alcohol dehydrogenase and acetaldehyde dehydrogenase convent to acetyl-CoA
    
    • builds up NADH and inhibits Krebs cycle
    • used for fat synthesis

Question 3

Citric acid cycle overview

Answer 3

• Acetyl CoA + oxaloacetate = citrate = isocitrate = a-ketoglutarate = succinyl-CoA = succinate = fumarate = malate = oxaloacetate
• Produce 2CO₂ + 3NADH + FADH₂ + GTP
• PDH produce Acetyl-CoA + CO₂ + NADH
• Total ATP:
  
  • 2.5 per NADH
  • 1.5 per FADH2
  • 1 per GTP
  • 12.5 ATP per pyruvate or 25 per glucose

Question 4

PDH regulation

Answer 4

• PDH kinase phosphorylates PDH to inhibit it
  
  • increase inhibition when ATP available
• PDH reactivated by pDH phosphatase when high levels of ADP
• ATP and NADH inhibit PDH

Question 5

Citric Acid Cycle Regulation

Answer 5

• Citrate synthase - ATP and NADH are allosteric inhibitors, both are products
  
  • also inhibited by citrate and Succinyl-CoA
• Isocitrate dehydrogenase - inhibited by ATP and NADH. ADP and NAD+ are activators and increase affinity for substrate
• a-ketoglutarate dehydrogenase complex - succinyl-CoA and NADH are inhibitors. ATP slows enzyme
  
  • stimulated by ADP and Calcium

Question 6

Electron transport chain overall

Answer 6

• proton gradient produced using flow of electrons
  
  • proton gradient creates power (proton-motive force)
• glycolysis in cytosol
• citric acid cycle in mitochondria
• oxidative phosphorylation in inner membrane of mitochondria
• protons moved from matrix to intermembrane space to make greater concentration gradient

Question 7

Electron Flow in ETC

Answer 7

• Complex I - Coenzyme Q becomes CoQH₂ and 4 protons pumped across membrane
  
  • NADH is now NAD+
• Complex II - FADH₂ oxidized to FAD (succinyl reaction occurs at the membrane) and CoQ reduced to CoQH2
  
  • no pumping
• Complex III - aka Cytochrome reductase - electrons from CoQ to cytochrome c
  
  • cytochromes - proteins with heme groups. Fe2+ and Fe3+ involved
  • Q cycle - increases proton gradiant across inner membrane
• Complex IV - cytochrome c oxidase - transfer electrons from cytochrome c to oxygen
  
  • oxygen forms water 2 protons moved across membrane

Question 8

Proton motive force

Answer 8

• uses electrochemical gradient to store energy
• used by ATP synthase to make ATP from ADP

Question 9

NADH Shuttles

Answer 9

• shuttle mechanisms - brings NADH from glycolysis into the mitochondria
• Glycerol 3-P shuttle - NADH used to form glycerol 3-P from DHAP in cytosol
  
  • glycerol 3-P dehydrogenase on surface of mit. membrane uses DHAP to make glycerol 3-P and FADH2
  • FADH2 goes on to make 1.5 ATP
• Malate-aspartate shuttle - Cytosolic oxaloacetate reduced to malate that crosses membrane
  
  • oxidize NADH to NAD+
  • malate into mitochondria
  • malate dehydrogenase reverse reaction to form NADH and oxaloacetate
  • NADH goes to make 2.5 ATP
  • oxaloacetate transaminase into aspartate and back into cytosol (can make oxaloacetate in cytosol)

Question 10

Chemiosmotic Coupling

Answer 10

• ATP synthase - spans entire inner membrane and into the matrix
• F₀ portion is the ion channel, protons back into matrix
• chemiosmotic coupling - chemical energy of gradient harnessed to phosphorylate ADP

Question 11

Conformational coupling

Answer 11

• ATP released by synthase as result of conformational change due to gradient
• portion of synthase acts as turbine to harness energy

Question 12

Regulation of Oxidative Phosphorylation

Answer 12

• respiratory control
  
  • increase O2 and ADP than make ATP
  • decrease O2 or ADP than no ATP production
  • ADP allosterically activates isocitrate dehydrogenase and increase CAC and NADH and FADH2
    
    • increase ETC and ATP synthase