BCHM-3050 Lecture Notes - Lecture 12: Oxidative Stress, Isoprene, Q Cycle
3 Jul 2018
School
Department
Course
Professor
Overview of oxidative energy generation
Little ATP generation = stage 1 and 2
Produce 10 mol NADH and 2 mol FADH total
Per mole glucose
§
○
•
Deoxidization of NADH and FADH = most energy of ATP synthesis
•
Oxidative Phosphorylation: inner mitochondrial membrane
Complex I, III, IV: pump protons into intermembrane space of
mitochondria
Create H+ gradient
○
•
Complex V: use E stored in gradient to drive ATP synthesis
•
E- carriers in respiratory chain
Chain stimulates flow of electrons
From low (-) reduction potential to high (+)
Exergonic
§
○
•
Flavoproteins: tightly bound FMN or FAD
Can link two electron and one electron processes
○
•
Iron sulfur proteins: nonheme iron complexed w thiol sulfurs
•
E- carriers:
Coenzyme Q (shuttles 2 e-)
○
Complex I: FMN
○
Complex II: FAD
Flavins are bound to protein complex
§
○
•
Complex I, II, III: non heme iron-sulfur clusters
•
Complex II and III = cytochromes w hemes (b, c, a)
3 b = II and III
○
C1 = III
○
A and A3 = IV
○
•
Iron-Sulfur Cluster
Reduction potentials vary depending on types of cluster
•
Types:
2 Fe-2S
○
3Fe-4S
Rare
§
○
4Fe-4S
○
•
Can carry 1 e-
•
Coenzyme Q
CoQ = oxidized form
•
CoQH = reduced form
•
Lipophilic e- carrier
Inside hydrophobic core of mitochondria (inner membrane)
○
Benzoquinone group + isoprene hydrophobic tail
○
•
Transfer 2e- in one step
Like riboflavin
○
•
Link b/w 2e- carriers and 1e- carrier
•
Cytochromes
C and C1 hemes: covalent bound to protein
•
A and A3 hemes: noncovalently attached to protein
Formyl group and isoprenoid modification
○
•
Classify bassed on absorption
•
Standard potential of major e- carriers
Transport of e- = series of coupled exergonic rxns
•
Energy is lost by e- and used to pump H+ out
As e- fall down their energy gradient they release energy
○
•
Complex I
One FMN and 8 iron sulfur clusters
•
2 e- donor (NADH) + Fe-S cluster that can carry 12-
Linked via FMN
○
•
Act as proton pump
Achieve via conformational changes
○
•
Complex II
Succinate dehydrogenase uses FAD to extract 2e- from succinate
TCA
○
2 e- from succinate => FAD => cluster of Fe-S => CoQ
○
•
Doesn’t pump H+ into intermembrane space
•
Coenzyme Q collect e- from multiple flavoproteins
Accept from ETF: ubiquinone oxidoreductase and glycerol-3-phosphate
dehydrogenase
•
Complex III
Catalyze transfer of e- from COQH to cytochrome C in intermembrane
space
•
Q cycle: 2e- donor transfers e- to 1e- acceptor
Req e- transfer from COQH in two stages
○
Complex III has two bindin sites for Q
Q1 and Q0
§
One electron moves through each site but ultimately end up in
ctrochrome c
§
○
•
Complex IV
Catalyze transfer of e- from reduced cytochrome c to O2
Pump 2 H+ into intermembrane space
○
•
P/O ratio
P/O ratio: number of ATP molecule synthesized per pair of e-
•
NADH = ~2.5
•
Oxidation of succinate =~1.5
•
Chemiosmotic coupling and ATP synthesis
H+ protons in intermembrane space = electrochemical gradient
Dissipate through complex V (ATP synthase)
Provide free E for ATP synthesis
§
○
•
Energy yield from Ox Phos (1 mol glucose)
4 moles of ATP + 10 mol NADH + 2 mol FADH = 34 ATP
•
Oxidative stress and reactive O2 specie
Oxidase: generate reactive oxygen specie (ROS)
Damage bio molecules
○
•
Prevent bio dmg via antioxidants or superoxide mutase
•
Chapter 14: ETC
Monday, June 18, 2018
9:58 PM
Document Summary
Little atp generation = stage 1 and 2. Produce 10 mol nadh and 2 mol fadh total. Deoxidization of nadh and fadh = most energy of atp synthesis. Complex i, iii, iv: pump protons into intermembrane space of mitochondria. Complex v: use e stored in gradient to drive atp synthesis. From low (-) reduction potential to high (+) Can link two electron and one electron processes. Iron sulfur proteins: nonheme iron complexed w thiol sulfurs. Complex i, ii, iii: non heme iron-sulfur clusters. Complex ii and iii = cytochromes w hemes (b, c, a) Reduction potentials vary depending on types of cluster. C and c1 hemes: covalent bound to protein. A and a3 hemes: noncovalently attached to protein. Transport of e- = series of coupled exergonic rxns. Energy is lost by e- and used to pump h+ out. As e- fall down their energy gradient they release energy. 2 e- donor (nadh) + fe-s cluster that can carry 12-
