Lect 5 Mitochondrial Bioenergetics Flashcards
What does amphibolic mean?
- Amphibolic = catabolism and anabolism
What energy nutrients is Acetyl CoA obtained from?
- CHO: Glu –> 2 Pyruvate –> 2 Acetyl CoA
- Lipids: TAG –> FA –> Acetyl CoA (B-Oxidation)
- Proteins: AAs –> Acetyl CoA
Acetyl CoA deltaG Value
-7.5 kcal/mol
Pyruvate Transport Into Mitochondria
Mitochondrial Pyruvate Carrier (MPC)
What is Pyruvate Dehyrogenase Complex’s function?
Catalyzes decarboxylation of pyruvate
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?
- PDC is always phosphorylated form (inactive)
- Glucose –> Lactate (instead of Acetyl CoA)
- Lactic Acidosis
- Avoid Alanine intake (converted to Pyruvate)
How is PDC Regulated?
- Regulation:
- Activate: Pyruvate, ADP, NAD+, CoA, Ca, Mg
- Inhibit: Acetyl CoA, NADH, ATP, Arsenite
TCA Product Conversions
- 1 NADH = 2.5 ATP
- 1 FADH2 = 1.5 ATP
- 1 GTP = 1 ATP
Why is TCA Analplerotic?
-
Anaplerotic: Reactions provide intermediates for replenishing TCA
- Degradation of AAs (replenish a-ketoglutarate, succinyl CoA, fumarate)
- Carboxylation of Pyruvate (replenish OAA)
TCA Cycle Disorders
- 2 - Oxoglutaric Aciduria
- Fumarase Deficiency
- Succinyl-CoA synthetase (SCS) deficiency
- SUCLA2
- SUCLG1
- Mitochondrial Depletion Syndrome
TCA Intermediates in Anabolic Pathways
- Citrate –> Lipid Synthesis
- OAA –> Glucose Synthesis
- OAA & a-Ketoglutarate –> AA Synthesis
What does Standard Redox Potential mean?
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’
What is delta E’ and delta G’ relationship?
Inversely related
deltaG’ = -nF(delta E’)
Highest delta E’ = Greatest negative deltaG’ and most spontaneous
What are the Goals of Ox Phos?
Transfer _
Establish _
Synthesize _
- Transfer e- from NADH and FADH2 –> O2
- Establish proton gradient across inner membrane
- Synthesize ATP
Establish Proton Gradient: Chemiosmotic Hypothesis
What factors constitute the PMF?
- 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
Synthesis of ATP
- 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
How is the Respiratory Chain Organized?
- 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)
There are 4 inhibitors of Complex I
“RAMP”
Rotenone
Amytal
Myxothiazol
Piericidin A
What is the inhibitor of Complex II?
Malonate
What is the Complex III Inhibitor?
Antimycin
What are the three Complex IV Inhibitors?
CO
Cyanide
H2S
What is an inhibitor of Complex V?
Oligomycin
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?
- 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
What is the importance of thermogenesis in Brown Adipose Tissue?
Important source of heat production during cold adaptation
It is rich in mitochondria and UCP-1 (uncoupleing protein-1) which uncouples OxPhos producing heat
Malate Aspartate Shuttle
Location?
Where does it start and with what?
- 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
Glycerophosphate Shuttle
Location: Skeletal Muscle
- Cytosolic NADH + DHAP –> Glycerol 3P (Crosses outer membrane)
- Glycerol 3P transfers e- to Mito-Matrix FAD –> FADH2 –> CoQ
