1
Q
ETC overview
A
the oxidation reactions are coupled to the transfer of e- (reduction) to the e- carriers NAD+ and FAD (oxidized)
2
Q
redox reactions in biological systems
A
represent transfer of H atoms
3
Q
mitochondria: outer membrane
A
permeabel to most ions and small molecules via small channels, porins
4
Q
mitochondria: inner membrane
A
impermeabel to most small ions, small and large molecules
5
Q
mitochondria: matrix
A
- TCA cycle enzymes
- FA oxidation enzymes
- mtDNA and mtRNA
- mitochondrial ribosomes
6
Q
mitochondria
A
transcriptional and translational machinery
7
Q
complexes imbedded in the inner membrane
A
complexes I, II, III, IV, V
-spans the whole membrane from side to side
8
Q
Complex V
A
enzyme ATP-synthase
9
Q
What is the only nonprotein carrier?
A
CoQ
10
Q
complex I
A
- NADH dehydrogenase
- accepts e- from glycolysis, TCA
- FMN, accepts H atoms to make FMNH2
- iron sulfur center
11
Q
complx II
A
- succinate dehydrogenase
- the only TCA enzyme embedded in the inner mitochondrial membrane
- FAD contains iron sulfur center
12
Q
CoQ
A
- ONLY nonprotein carrier
- quinine derivative with long hydrophobic tail
13
Q
Complex III
A
- cyt b
- cty c1
14
Q
complex IV
A
- cyt a
- cyt a3
15
Q
cyt c
A
freely moving in the inter membrane space
16
Q
Cyt iron
A
reversibly converted from ferric (Fe3+) to ferrous (Fe2+) form
17
Q
Complex IV
A
- cyt a+a3 or cytochrome c oxidase
- Cu required for e- transport
- only complex in which the heme Fe has a site that directly reacts with O2
- e- moves from Cua to Cyt a3
18
Q
Transfer of e- down the ETC
A
driven because NADH is a strong electron do not, and O2 is a strong electron acceptor
19
Q
oxidative phosphorylation: the chemiosmotic hypothesis
A
- electrical gradient
- pH gradient
- this energy created by this used to drive ATP synthesis
- proton gradient serves as common intermediate that couples oxidation to phosphorylation
20
Q
Complex V
A
- ATP-synthase
- multisubunit enzyme
- domain Fo spans the inner mitochondrial membrane
- domain F1-extramembranous that appears as a sphere that protrudes into the matrix
21
Q
ATP-synthase function
A
- protons flow back through Fo, driven by gradient, which drives rotation of F1 domain
- rotation of F1 causes conformational change that allow it to bind ATP +Pi, and phosphorylate ADP to ATP and release ATP
22
Q
inhibition of ETC
A
- blocking e- transfer by any one of these inhibitors stops electron flow from substrate to O2 because the reactions of ETC are tightly coupled like meshed gears
- lactate build up, highly aerobic tissues affected
23
Q
Complex 1 inhibitor: amytal
A
- barbiturate
- proper drug usage
24
Q
Complex I inhibitor: rotenon
A
used as an insecticide, piscicide, and pesticide
25
Complex III inhibitor: antimycin A
piscicide
26
Complex IV inhibitor: cyanide (CN-)
- irreversibly binds to the Fe3+ in the heme group of Cyt C-oxidase
- house fires
27
Complex IV inhibitor: CO2
-binds irreversibly however the primary toxicity is associated with the tight binding to hemoglobin
28
Complex IV inhibitor: sodium azide (NaN3)
-binds similarly to cyanide to the Fe3+ of iron in cytochrome. propellant in airbags, explosives, in lab as antimicrobial perservative
29
Complex V inhibitor: Oligomycin
binds to the Fo domain closing the proton channel leading back into the matrix, shutting down ATP synthesis. a tool to study ATP in the lab
30
coupling in normal mitochondria
ATP synthesis is coupled to e- transport through the H+ gradient
31
uncoupling
allowing the H+ to flow back through the membrane without generation of ATP
32
uncoupling: naturally
UCPs localized in the inner mitochondrial membrane
33
synthetic uncouplers
nonprotein compounds that increase he permeability of the inner mitochondrial membrane to H+
34
UCPs
- allow H+ to flow back into matrix
| - free energy released as heat (non shivering thermogenesis)
35
UCP1 (thermogenin)
found in brown adipose tissue of mammals
36
UCP2, 3, 4, and 5
found in other tissues but function not understood
37
2,4-dinitrophenol
- synthetic uncoupler
- weight loss drug
- fatal hyperthermia
38
salicylic acid
- causes uncoupling
- aspirin
- overdoses will cause high fever, profuse sweating, and can be fatal
39
Reactive Oxygen Species (ROS)
- unavoidable by product of ETC
- incomplete reduction of oxygen to water
- can damage proteins, lipids, DNA, RNA, etc, present in mitochondria
- can increase production of free radicals
40
mtDNA
- encodes 12 of 120 proteins
- constant exposure to ROS
- oxidative defects in oxidative phosphorylation
- severly affect highly aerobic tissues
41
Leber Hereditary Optic Neuropathy (LHON)
MERRF, and MELAS. Leigh syndrome can result from mutations in tDNA or nuclear DNA
42
mitochondrial in apoptosis
- intrinsic
- pores
- allow Cyt C to be released
- caspases (proteolytic enzymes)
- cause cleavage of key proteins
43
iron deficiency
- several proteins in the ETC require iron
| - tiredness
44
Leber hereditary optic neuropathy (LHON)
optic neuropathy
| optic atrophy
45
Neurogenic muscle weakenss ataxia retinitis pigmentosa (NARP)
retinal dystrophy
| cone or cone-rod dystrophy
46
Maternally inherited Leigh disease (MILS)
RPE dystrophy
| Optic Atrophy
47
Mitochondrial encephalopathy lactic acidosis stroke like episodes (MELAS)
maculopathy
Cone-Rod dystrophy
Hemianopsia
48
Maternally inherited diabetes and deafness (MIDD)
pattern maculopathy
| pigmentary retinopathy
49
Myoclonic epilepsy ragged red fibers (MERRF)
Optic atrophy
| Mild pigmentary retinopathy
50
Kearns-Sayre Syndrome (KSS)
Pigmentary retinopathy
| strabismus ptosis
51
Chronic progressive extraocular ophthalmoplegia (CPEO)
Ptosis
Strabismus
Ophthalmoplegia
Biochem BLOCK 2
flashcards
Decks in class (14)
# Cards
-
TCA (Krebs Cycle)57
-
Cholestero, Lipoprotein Metabolism And Steroids61
-
Deevska-Block 2166
-
YOUNGER BLOCK 262
-
ETC51
-
gluconeogensis (GNG)32
-
glycogen72
-
Pentose Phosphate pathway and NADPH40
-
Metabolism of other Mono-and Disaccharides34
-
Lipid classification34
-
Lipid Digestion and Absorption38
-
complex lipids112
-
Fatty acid synthesis50
-
Fatty Acid Metabolism100
