Aerobic Catabolism Flashcards
Where does aerobic catabolism take place?
mitochondria
How does pyruvate become acetyl-coA?
-catalyzed by the pyruvate dehydrogenase complex, in the mitochondria
-large, highly regulated multi-enzyme complex
-OXIDATIVE DECARBOXYLATION
What are the 3 subunits of the PDH complex?
E1- pyruvate dehydrogenase
E2- dihydrolipoyl transacetylase
E3- dihydrolipoyl dehydrogenase
How is acetyl co-A oxidized? GENERAL
-requires oxygen
-releases acetyl carbons as CO2
-generates lots of ATP
What are the two phases of oxidation of acetyl-CoA?
-Krebs cycle: releases CO2 and passes electrons to NAD+ and FAD to generate NADH and FADH2
-Electron transfer and oxidative phosphorylation: passes electrons from NADH and FADH2 to oxygen, uses energy to generate ATP
What is the function of the Krebs cycle in aerobic respiration?
-oxidation of the acetyl group of acetyl-CoA
-the acetyl group of acetyl-CoA is oxidized to CO2
– results in reduction of NAD+ to NADH and FAD to FADH2
–these are fed into the electron transfer chain provide energy for ATP synthesis
How is acetyl-CoA made?
-low concentration
-produced from:
–carbohydrate degradation via glucose and glycolysis (plus PDH reaction)
–triglyceride degradation via fatty acids and B-oxidation
–protein degradation (some amino acids)
What are the 8 steps of glycolysis? GENERAL
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase
- a-ketoglutarate dehydrogenase complex
- succinyl-CoA synthetase
- Succinate dehydrogenase
- Fumarase
- Malate dehydrogenase
What type of pathway is the Krebs cycle?
Amphibolic, involved In both catabolic and anabolic pathways:
Catabolic- aerobic respiration
Anabolic- intermediates for fatty acid and amino acid synthesis, gluconeogensis
What is a competitive inhibitor of succinate dehydrogenase?
malonate
What is gifblaar?
-South African plant contains fluroracetate, which can be metabolized to flurocitrate in the mitochondria
-potent competitive inhibitor of aconite
Give an overview of acetyl-CoA oxidation.
-electrons from reduced co-enzymes are passed through the electron transfer chain
-each passes electrons to the next member of the chain, which becomes reduced as the donor becomes oxidized
-the energy released is used to pump protons across the inner membrane
-the proton gradient drives ATP synthesis
-source of reduced co-enzymes mostly Krebs, some from cytoplasm
Where does oxidative phosphorylation occur?
mitochondria
What are the key points of the mitochondria?
-outer membrane freely permeable to small molecules
-inner membrane permeable
-Krebs cycle occurs in the matrix (except step 6)
-electron transfer and oxidative phosphorylation in the inner membrane
What are the two phases of oxidative phosphorylation?
-electron transfer reactions
– electrons passed from NADH and FADH2 to oxygen- generates a proton gradient
-proton gradient used to drive ATP synthesis
How do electron transfer reactions in the Mitochondria occur?
-electrons are funneled to universal electron acceptors (NAD+->NADH etc.)
-electrons pass through a series of membrane-bound electron carriers
-oxygen is the final electron acceptor
What are the 3 electron acceptors in the electron transfer chain?
-Ubiquinone (coenzyme Q/Q)
-Cytochromes
-Iron-sulfur proteins
Explain ubiquinone.
-hydrophobic, stays buried in the mitochondrial membrane
-accepts one e- at a time
Explain cytochromes.
Three types in mitochondria:
-A
-B
-C
tightly or covalently bound heme group (prosthetic group)
What is a heme?
-contain porphyrin ring
–4 5-carbon rings, containing nitrogen with a central Fe atom to accept and give up electrons
Explain Iron-sulfur proteins.
-contain iron as iron-sulfur centers
-various arrangements of cys-S, inorganic S, and Fe
What is the order of electron carriers?
NADH
Q
Cyt b
Cyt C1
Cyt C
Cyt A
Cyt A3
O2
What are electron carrier inhibitors?
Rotenone: backs up at Q
Antimycin A: backs up at Cyt C1
CN- or CO: backs up at O2
What are the carriers function in multienzyme complexes? (4 complexes)
1: NADH to Q
2: Succinate to Q
3: Q to Cyt C
4: Cyt C to O2
Explain complex 1:
-also known as NADH dehydrogenase
-at least 43 polypeptides
-contains FMN and at least 6 iron-sulfur centers
-pumps 4 protons from matrix to the inter membrane space
Explain complex II:
-succinate dehydrogenase (krebs enzyme)
-located in inner mitochondrial membrane (all others in matrix)
-four subunits, 5 prosthetic groups
-electrons passed to Q from QH2
-no protons pumped
Explain complex 3.
-transfer of electrons from QH2 to cytochrome c
-transports protons from the matrix to the intermembrane space
-four protons transported for every two electrons transferred to cyt c
-involves a dimer of complex III
Explain complex 4.
-carries electrons from cyt c to final electron acceptor, O2
-large complex of 13 subunits containing prosthetic groups, heme, iron-sulfur centers and copper
-pumps out 4 protons (two per electron pair)
How many protons are pumped total through complexes?
for each electron pair, 10 protons are pumped
How are ROS generated during oxidative phosphorylation?
-Reactive oxygen species
-passage of electrons from complex I to QH2, and from QH2 to complex III involve generation of ubismiquinone, this can pass an electron to O2
-creates a superoxide free radical- very reactive
How is oxidative damage prevented from O2?
-superoxide dismutase:
peroxidases, remember GSH is kept in reduced state by glutathione reducaste, using NADPH from pentose phosphate pathway
How is glutathione maintain in the reduced state?
NADPH from the pentose phosphate pathway
What is the chemisomotic model of ATP synthesis?
mechanism of electron transfer being coupled to ATP synthesis
-How a concentration gradient of protons is transformed into ATP
What is the basis of ATP synthesis?
-intact mitochondria needed
-electron transfer inhibited by inhibitors of ATP synthase
-Treatment with detergent uncouples
-Dinitrophenol uncouples
How are electron transfer and ATP synthesis tightly coupled?
O2 consumption and ATP synthesis:
-only in presence of substrate
-inhibited when electron transfer inhibited
How can electron transfer and ATP synthesis be uncoupled?
DNP
-dissipates proton gradient by carrying protons across the inner membrane
-allows electron transfer without ATP synthesis
-energy dissipated as heat
What are the two functional domains of ATP synthase?
F0
F1
combined to perform rotational catalysis
What are the 3 conformations of ATP synthase?
Open (O) low affinity
Loose-binding (L)
Tight-binding (T)
interconversions driven by rotation
Explain ATP synthesis.
-ADP and Pi bind to an L site
-rotation converts L to T conformation; ATP synthesized
-further rotation converts T to conformation of O, releasing ATP
-cycle repeats
What are ADP-ATP and phosphate translocators?
-for every 4 protons, one used for Pi transport, 3 for ATP synthesis
-ADP-ATP translocator drive by potential difference
What is the P/O ratio?
-moles of phosphate consumed per mole of oxygen atoms consumed
-max measured: 2.5 for NADH, 1.5 for FADH2
–2.5 molecules of ATP per NADH, 1.5 molecules of ATP per FADH2
How much ATP is produced from each acetyl-coA?
-3 molecules of NADH
-1 molecule of FADH2
-1 molecule of ATP
TOTAL: approximately 10 molecules of ATP for each acetyl coA
At what age is most brown adipose tissue found? How can it be increased? What protein uncouples it?
newborns
cold temperatures
UCP1
