Lecture 4: Bioenergetics Flashcards
What three molecules are associated with substrate lvl phosphorylation?
- Phosphoenolpyruvate
- 1,3-biphosphoglycerate
- Phosphocreatine
Pyruvate Dehydrogenase Complex (kinase and phosphatase)
- Pyruvate Dehydrogenase Kinase
(+) - ACoA, NADH, ATP
(-) - Pyruvate, CoA, NAD, ADP - Pyruvate Dehydrogenase Phosphatase
(+) - high Ca/Mg
PDC Phosphatase Deficiency
- ALWAYS phosphorylated (inactive)
- Glucose to Lactate (Lactic Acidosis)
- restrict Alanine intake
What are the 3 regulated enzymes of the TCA cycle?
- Citrate Synthase
- Isocitrate Dehydrogenase (NADH)
- a-ketoglutarate Dehydrogenase (NADH)
What is the Rate Limiting Step of the TCA Cycle?
Isocitrate Dehydrogenase
Eo’ and delta G
- lower Eo’ –> lower electron deficiency, gives them up easily to pair w/higher Eo’
- inversely related to delta G
What two factors constitute the proton-motive force?
- pH gradient
2. membrane potential
Inhibitors of Complex I
amytal, rotenone, myxothiazol, piericidin A
- barbituates
Inhibitors of Complex II
malonate
Inhibitors of Complex III
antimycin
Inhibitors of Complex IV
CO, cyanide, H2S
Inhibitors of Complex V
oligomycin
ETC Uncoupling molecules for: Membrane Damage, Proton Carriers, Proton Channel
- Membrane Damage: AraC, AZT
- Proton Carriers: DNP, Aspirin
- Proton Channel: Thermogenin (UCP-1)
Malate-Aspartate Shuttle
- move NADH into mito matrix via malate
- reversible
- provides NADH to Complex I
- heart, liver, kidney
Glycerophosphate Shuttle
- move NADH into mito matrix via glycerol-3-phosphate
- irreversible
- provides FADH2 to coenzyme Q
- skeletal muscle, brain
Acetyl CoA in other metabolic pathways
Sole building block for the synthesis of lipids such as fatty acids and isoprenoids (sterols and steroid hormones)
What is coenzyme A?
Activator of acyl groups
Activation of acyl groups w/CoA facilitates transacylation, condensation, oxidation-reduction reactions
How much energy do we get from glucose vs fatty acids? (ATP)
FA provides 129 ATP compared to glucose providing 36-38
What is Pyruvate Dehydrogenase Deficiency (neonatal lactic acidosis) and how can it be treated?
- Defects in PDC (E1)
- Neonatal Lactic Acidosis (high serum lvls of pyruvate and lactate)
- Administer vitamin B1, lipoic acid, biotin
Arsenite and how it affects lipoic acid
- links SH bonds in lipoic acid
- suicide inhibitor, binds thiol group irreversibly
- takes time to poison person; detected in hair
What is Beriberi and Wernicke-Korsakoff Syndrome a deficiency of?
insufficient thiamine
How does citrate affect rate-limiting enzymes?
- indicates ATP-rich state (inhibit PFK1 in glycolysis)
- promotes storage of excess energy as fat (promotes ACoA carboxylase)
- helps maintain energy charge of cells in desired range
ATP:ADP and NADH:NAD ratio range
0.8-0.95
How does rat poison inhibit the TCA cycle?
- fluoroacetate inhibits TCA cycle, forms fluorocitrate (citrate analog)
- competitive inhibitor of anconitase; leads to citrate buildup
- inhibits citrate synthase, citrate buildup inhibits glycolysis
Succinyl CoA in heme synthesis
- condensation of succinyl-CoA and glycine, w/decarboxylation, generates ALA as first step of heme biosynthesis
- rxn catalized by ALA synthase, rate limiting enzyme of heme biosynthesis (B6 cofactor)
What is ferredoxin?
- small proteins (electron carriers) in mit cytochrome P-450
- varieties are used from heme and steroid hormones
Ubiquinone Radical
- can pass electron to O2 to generate free radical superoxide
- superoxide dismutase converts superoxide to H2O2
Cytochrome-c and apoptosis
- cytochrome-c released via mitochondrial permeability transition pore complex
- biochemical marker for cells undergoing apoptosis
What is rotenone?
- naturally occurring pesticide (fish poison)
- potent inhibitor of Complex 1 (treat w/vitamin K)
What is the difference between cyanide vs CO as an inhibitor?
cyanide - noncompetitive inhibitor
CO - competitive inhibitor
Aspirin Overdose
- acute poisoning causes hypothermia
- DNP can also cause hypothermia
Hypoxia and ATP preservation
- decrease activity of respiratory chain/proton motive force
- low pH in mito matrix cause IF1 (small inhib protein) to bind to ATP Synthase and prevent hydrolysis of ATP
