Inner membrane
porin is at?
Outer membrane
The serial endosymbiotic theory hypothesis that eukaryotic cell evolved from?
a symbiotic association of prokaryotes-endosymbiosis
Ech mitochondrion has its own DNA, RNA and 12s & 16s ribosomes?
YestRnA synthasesalso, 4 of 64 codons are different
complex I-IV
ETC
for Delta G0 to be (-)
need delta E0
more (+) E'0 values is....
the better electron acceptors is - They accept e and become reduced
the largest prot. components of the ETC?
NADH dehydrogenase
Prot + heme prosthetic groupseveral classes: a, b, caccept 1 d at a timeabsorb visible light differently if oxidized or reduced
Cytochromes
Fe but not in porphyrin ring - non-heme several complex configurations- a prosthetic group of port bound via cysteine sulfurs1 e transfersfixed in inner membrane
Iron-sulfur prot
non-prot components of ETCcan carry both 1 e and 1 protonQ <-> QH. <-> QH2
Ubiquinone (Q)the intermediate is unstable
What is the Complex I
NADH: Ubiquinone Oxidoreductase
pumps 4 H+ to Intermemb. space (IMS)processes 2 e at a time (only e)
Complex I
What is the complex II?
Succinate Dehydrogenase
NO transfer of H+ to IMSprocesses 2 e at a time
Complex II
What is the Complex III?
Cytochrome bc1
Pumps 4 H+ to IMScan only take 1 e at a time - called step-down transformer 2 e unit (FADH2, NADH) to 1 e unit (cytochrome c)
Complex III
What is the complex IV?
Cytochrome Oxidase
pump 4 H+ to IMS (2/NADH)
Complex IV
O2 must wait for how many e to form 2 water
4 electron
what is the total of H+ that transfer from complex I--> complex IV
10
what is the other importance of Cytochrome c in the other process?
apoptosis
4cyt(red) + O2 --> ?
4cyt(ox) + 2H2O
E transport and ATP synthesis need to be?
coupled
How proton flow in the mitochondria (proton gradient)?
from matrix pump out pass the inner membrane to the inner mitochondrial memb
what is the 2 part of proton gradient?
1. chemical gradient delta pH. the pH outside matrix is 1.4 units lower than inside2. charge gradient delta y (membr potential is 0.14 V, the outside being (+)
inner membr., protrudes into matrixvery large - F0 +F1 subunitproton gradient rotate y subunitmove like a water wheel
Complex V - ATP synthase
what move through complex V
proton move through F0 to make the rotation (gradient)
As H+ flows through and y rotates within F1, it interacts with beta subunit and convert?
b-ATP --> emptyb-ADP + Pi --> ATP (ATP synthesis)b-empty --> b-ADP + Pi
ADP/ATP antiporterH+/H2PO4- symporterCan also use proton gradient to drive other transport
Nucleotide Exchange
what are 2 agents that interfere with (ETC) oxidative phosphorylation?
cyanide - target cytochrome oxidasecarbon monoxide - cytochrome oxidase
what is type interference of DNP?
Uncoupling
what happen in the present of DNP (2,4-dinitrophenol)?
e transport from NADH to O2 is normal but no ATP synthesis --> proton gradient is disrupted --> further increase O2 consumption and NADH oxidaton
3 way to disrupt the ATP synthesis?
Blocking ETCblocking ATP synthaseuncoupling ETC and ATP synthesis
what chemical can blocking ETC at any point to stops ATP synthesis is?
cyanide
how to blocking ATP synthase to stop electron flow?
oligomycin-blocks F0
interfere via chemica holes in membrane - stops ATP syntheseis (no proton gradient) but not e flow (energy ususally used to produce ATP is given off at heat)
Uncoupling ETC and ATP synthesis
One of the biological uncoupler that provide alternative pore for proton?
Thermogenin
The mitochondrial genome is small and circular?
TRUE
Mitochondrial division can?
can divide in response to energy needmust divide with each cell division
..O2- = superoxideH2O2 = hydrogen peroxideHO. = hydroxyl radical
Reactive Oxygen species
.NO = nitric oxideONOO- = peroxynitrite.NO2 = nitrogen dioxide
Reactive Nitrogen Species
Most free radicals are generated via normal?
metabolic processes
3 major sources of in Vivo ROS production?
1. by-product of e transport2.Reaction of O2 with metals3. Product of enzymatic processes
Most cellular oxidative stress comes from?
Mitochondrial mismanagement of oxygen reduciton
Major source of superoxide radical?
Reaction of .Q- with O2
short half-life-NANO secondhighly reactive with prot nucleic acids, lipids resulting in dysfunction/mutation
Properties of ROS
what are some good ROS?
Myeloperoxidase Nitric Oxide Synthase NADPH Oxidase Xanthine Oxidase produces hydrogen peroxide
what is some ROS formation and metal?
Fenton RxnHaber-Weiss rxnMetal-catalyzed Haber-Weiss rxn
what do we know about Hydroxyl Radical (HO.)?
Most reactive free redicalReacts with all biomolecules via hydrogen abstraction and additionResult in lipid peroxidation, DNA strand break, prot oxidation & degradation
What are markers of Oxidative dammage
Lipid Oxidation+advanced lipoxidation endproducts (ALE)Protein OxidationDNA Oxidation+ALEs and nitrotyrosine have been found in atherosclerotic lipoproteins and Alzheimer's plaques
What is the relationship of ROS and diabetes?
ROS react with carb to make reactive carbonyls that react with prot and form adducts and cross links:AGEs (Advanced Glycation End-products)
Receptors of AGEs is ?
RAGEs
Excess glucose also contributes to ROS production via what pathway?
Polyol pathway
What does the Polyol pathway do?
contributes to ROS by depleting NADPH needed to help neutralize itProduce sugar alcohol - sorbitol ( build up in the eye -> cataract)
Anti-Oxidants
EnxymesVitamin & free radical scavengesREpair systemsMetal sequestration
Aqueous phaseChain-breaking anti-oxidant
Vitamin C
Lipid phasechain-breaking anti-oxidant
Vitamin E
Lipid phasesinglet oxygen scavenger
Vitamin A
HIPAA stands for