Lect 5 Mitochondrial Bioenergetics

Question 1

What does amphibolic mean?

Answer 1

• Amphibolic = catabolism and anabolism

Question 2

What energy nutrients is Acetyl CoA obtained from?

Answer 2

• CHO: Glu –> 2 Pyruvate –> 2 Acetyl CoA
• Lipids: TAG –> FA –> Acetyl CoA (B-Oxidation)
• Proteins: AAs –> Acetyl CoA

Question 3

Acetyl CoA deltaG Value

Answer 3

-7.5 kcal/mol

Question 4

Pyruvate Transport Into Mitochondria

Answer 4

Mitochondrial Pyruvate Carrier (MPC)

Question 5

What is Pyruvate Dehyrogenase Complex’s function?

Answer 5

Catalyzes decarboxylation of pyruvate

Question 6

What is the Clinical Importance of PDC if there is a Phosphatase Deficiency

Glucose is turned into what instead? Causing?

What should patients with this deficiency avoid?

Answer 6

• PDC is always phosphorylated form (inactive)
• Glucose –> Lactate (instead of Acetyl CoA)
  
  • Lactic Acidosis
• Avoid Alanine intake (converted to Pyruvate)

Question 7

How is PDC Regulated?

Answer 7

• Regulation:
  
  • Activate: Pyruvate, ADP, NAD+, CoA, Ca, Mg
  • Inhibit: Acetyl CoA, NADH, ATP, Arsenite

Question 8

TCA Product Conversions

Answer 8

• 1 NADH = 2.5 ATP
• 1 FADH2 = 1.5 ATP
• 1 GTP = 1 ATP

Question 9

Why is TCA Analplerotic?

Answer 9

• Anaplerotic: Reactions provide intermediates for replenishing TCA
  
  • Degradation of AAs (replenish a-ketoglutarate, succinyl CoA, fumarate)
  • Carboxylation of Pyruvate (replenish OAA)

Question 10

TCA Cycle Disorders

Answer 10

• 2 - Oxoglutaric Aciduria
• Fumarase Deficiency
• Succinyl-CoA synthetase (SCS) deficiency
  
  • SUCLA2
  • SUCLG1
• Mitochondrial Depletion Syndrome

Question 11

TCA Intermediates in Anabolic Pathways

Answer 11

• Citrate –> Lipid Synthesis
• OAA –> Glucose Synthesis
• OAA & a-Ketoglutarate –> AA Synthesis

Question 12

What does Standard Redox Potential mean?

Answer 12

Eo’ –> Standard Redox Potential

• Measure of the affinity of a redox pair of e-
• Lower Eo’ has lower affinity for e- and gives them up to redox pair with higher Eo’

Question 13

What is delta E’ and delta G’ relationship?

Answer 13

Inversely related

deltaG’ = -nF(delta E’)

Highest delta E^’ = Greatest negative deltaG^’ and most spontaneous

Question 14

What are the Goals of Ox Phos?

Transfer _

Establish _

Synthesize _

Answer 14

• Transfer e- from NADH and FADH2 –> O2
• Establish proton gradient across inner membrane
• Synthesize ATP

Question 15

Establish Proton Gradient: Chemiosmotic Hypothesis

What factors constitute the PMF?

Answer 15

• e- transfer –> pumping of H+ from matrix to intermembrane space
• 2 factors constitute Proton Motive Force (PMF) driving ATP synthesis (Complex V)
  
  • pH gradient and membrane potential

Question 16

Synthesis of ATP

Answer 16

• ATP Synthase (Complex V)
  
  • Harness energy in PMF and uses power (7.3 kcal/mol) to form ADP + Pi –> ATP
  • Inhibitors: Oligomycin disrupts proton transport

Question 17

How is the Respiratory Chain Organized?

Answer 17

• Complex I (NADH; Pump H+) & Complex II (FADH2) –> CoQ (Mobile Carrier)
• CoQ –> Complex III (Pump H+) –> Cytochrome C (Mobile Carrier)
• Cytochrome C –> Complex IV (1/2 O2 –> H2O; Pump H+)
• Complex V (ATP Synthase)

Question 18

There are 4 inhibitors of Complex I

“RAMP”

Answer 18

Rotenone

Amytal

Myxothiazol

Piericidin A

Question 19

What is the inhibitor of Complex II?

Answer 19

Malonate

Question 20

What is the Complex III Inhibitor?

Answer 20

Antimycin

Question 21

What are the three Complex IV Inhibitors?

Answer 21

CO

Cyanide

H₂S

Question 22

What is an inhibitor of Complex V?

Answer 22

Oligomycin

Question 23

What is OxPhos Uncoupling?

It can occur in multiple ways, the _ can be damaged, _ channels can be used, and _ carriers are used (examples?)

What is the effect of ATP synthase inhibition?

Answer 23

• Proton Gradient Disrupted –> H+ reenter matrix –> Block ATP Synthesis
• Membrane Damage; Proton Channel: Thermogenin; and Proton Carriers: DNP, Aspirin
• Heat generation from TCA cycle and e- transfer to O2 being accelerated

Question 24

What is the importance of thermogenesis in Brown Adipose Tissue?

Answer 24

Important source of heat production during cold adaptation

It is rich in mitochondria and UCP-1 (uncoupleing protein-1) which uncouples OxPhos producing heat

Question 25

Malate Aspartate Shuttle

Location?

Where does it start and with what?

Answer 25

• Location: Heart, Liver, Kidneys
• Cytosolic NADH + OAA –> Malate (Crosses outer membrane)
• Malate/a-Ketoglutarate antiporter (inner membrane)
• Matrix NAD+ + Malate –> OAA and Mito-Matrix NADH –> Complex I

Question 26

Glycerophosphate Shuttle

Answer 26

Location: Skeletal Muscle

• Cytosolic NADH + DHAP –> Glycerol 3P (Crosses outer membrane)
• Glycerol 3P transfers e- to Mito-Matrix FAD –> FADH2 –> CoQ