Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
23 Cards in this Set
- Front
- Back
|
Mitochondria:
site of what processes? permeability? |
Site of Kreb's cycle, ETC, and OP
-Glycolysis occurs in cytosol -outer membrane allows diffusion of molecules up to 10 kb -Inner membrane is VERY impermeable: only allows water, O2, CO2 to diffuse. NADH (made in glycolysis), ATP, Pi, ADP, H+, and Ca2+ have to be transported across= driving force behind ATP synthesis -AA, fatty acids, and glycerol that are converted to aceytl CoA are transported across the inner membrane as well |
|
|
Transport of NADH into mitochondrial matrix from cytosol
|
Uses Malate-Aspartate shuttle
-put electrons from NADH on to oxaloacetate to make malate, then shuttle malate across membrane in a transporter; malate converted to oxaloacetate and reduces NAD+ to NADH -NADH oxidized in ETC -oxaloacetate converted to Asp inside matrix and Asp is moved out into cytosol where its converted back to oxaloacetate: recycling of NADH; NAD+ stays out in cytosol **Yield: 3 ATP/NADH **REVERSIBLE |
|
|
Transport of NADH into ETC in brain and skeletal muscle
|
Uses the glycerophosphate shuttle in brain and skeletal muscle (in addition to Malate-Asp shuttle)
-Oxidation of NADH to reduce FAD to FADH2, reduction of UQ to UQH2 to make Oxygen -NADH produced in cytosol used to reduce dihyroxyacetone phosphate (from glycolysis) to alpha-glycerol phosphate -alpha-Glycerol Phosphate oxidized by a flavoprotein to produce dihydroxyacetone phosphate and FADH2 that is oxidized in the ETC **Yield: 2 ATP/NADH **IRREVERSIBLE |
|
|
The Chemiosmotic Hypothesis
|
The free energy of electron transport is conserved by pumping H+ from matrix to inner membrane space to create an electrochemical (more negative in matrix) and pH gradient (proton-motive force, more alkaline in matrix) that drives ATP synthesis
-10 H+ are pumped into inner membrane space for eachS pair of electrons from NADH |
|
|
Standard Reduction Potential
|
-ease that electron donor gives up its electrons to the e acceptor
-Electrons in the ETC pass from lower to higher standard reduction potential in a chain of redox cofactors -cofactors become more selfish with electrons as they are passed from complex I to III to IV or from II to III to IV |
|
|
ETC: Complex I
cofactors enzyme electron acceptor inhibitors intermediates that feed into it to make NADH that complex I uses |
Contains cofactors:
FMN Iron-sulfur clusters (Fe-S), up to 7 Enzyme: NADH dehydrogenase Electron acceptor: UQ/CoQ -4 protons pumped into inner membrane space from 1 NADH -electrons passed to CoQ, it picks up 2 protons from matrix and is reduced to UQH2 -inhibited by: Rotenone -NADH formed from intermediates of: Kreb's cycle:malate, alpha-ketogluterate, isocitrate (malate-asp shuttling) Fatty acid oxidation: b-hyroxybutyrate and b-hydroxyacyl CoA |
|
|
ETC: Complex II
cofactors enzyme electron acceptor intermediates that form FAD |
**does NOT act as a proton pump...why we only get 2 ATP/NADH (for each FADH2) from complex II
Contains cofactors: FAD (Covelent tranfer of electrons) Fe-S clusters heme: (cyt b560) Enzyme: succinate dehydrogenase electron acceptor: UQ/CoQ *3 places FAD fed into in complex II to reduce UQ 1. uses glycerophosphate dehydrogenase shuttle (glycerol 3-P feeds into FAD from inner membrane space) to reduce UQ. a-Glycerol phosphate comes from glycerol released during hydrolysis of triacylglerols. Transfers electrons from FAD to FADH2 then reduces UQ to UQH2 2. Succinate (from Kreb's cycle) feeds FAD--> FeS-->UQ (from matrix) 3. fatty acid oxidase complex: fatty acyl CoA (from b-oxidation of fatty acids) feeds FAD-> ETF-> FeS/FAD-> reduces UQ (matrix) -feeding intermediates: Kreb's cycle: succinate Fatty acid oxidation: fatty acyl CoA -a-glycerol phosphate (from triacylglyercide hydrolysis) |
|
|
Role of Coenzyme Q
|
-CoQ, Ubiquinone
-shuttles electrons b/t Complexes I or II to III -can accept/donate 1 or 2 electrons -can transfer 2 electrons from NADH (QH2, ubiquinol, reduced/hydroquinone form) -can transfer 1 electron from cytochromes in complex III (QH or ubisemiquinone, radical form) Complex I: Accepts electrons from FMNH2 Complex II: accepts electrons from FADH2 |
|
|
ETC: Complex III
cofactors Mechanism for how H+ is pumped Inhibitors |
Contains cofactors:
1 Fe-S cluster 2 b hemes 1 c heme -pumps 4 H+ via the Q cycle Q cycle: 2 Q molecules involved, one from Complex I and one from Complex III to produce 2 QH2 molecules -4H+ released from 2 QH2 and are pumped into inner membrane space --2 cyt c reduced as a result: cytochrome c shuttles electrons from Complex III to IV** -inhibitors: Antimycin A, myxothiazol, stigmatellin |
|
|
ETC: Complex IV
cofactors enzyme products made/H+ pumped inhibitors |
Contains cofactors:
2 a hemes 2 Cu-clusters Enzyme: cyt c oxidase conversion of 1/2 O2 to water -Pumps 2 H+ inhibitors: Carbon Monoxide, Cyanide (gas/hydrogen, and postassium forms), and sodium azide (N3-) |
|
|
Flavoproteins as redox cofactors in ETC
|
FMN (complex I) or FAD (complex II)
-can transfer 1 or 2 electrons at a time, so act as intermediates in e transfers that only involve 1 electron at a time |
|
|
Fe-S complexes as redox cofactors in ETC
|
oxidized state: Fe3+
reduced state Fe2+ standard reduction potential depends on oxidized state and associated protein (bound to Cys) |
|
|
Heme groups as redox cofactors in ETC
|
-function in cytochromes
-heme iron is reduced and oxidized b/t Fe2+ and Fe3+ states during electron transport |
|
|
Complex V
alt. names location structure function to form ATP |
Other names: ATP synthase, F1F0-ATPase
-driven by electrochemical gradient generated by H+ translocation into intermembrane space -embedded in innermembrane, F1 particle sticks into mito matrix -F1: 3 alpha-beta dimers and 1 central gamma unit. 3 binding sites b/t dimers. 1 delta subunit connecting F0 b subunit, 1 e subunit to connect gamma rod to c subunit of F0. -F0: c subunits form a ring structure and change conformation when they are DEprotonated and rotate (c-terminal helix rotates 140 degrees). Physical spinning of c subunit causes central gamma F1 stock to spin -rotation of gamma subunit causes conformational change in F1 binding sites to induce ADP+ Pi to form ATP (PHYSICAL change in active site conformation) 1. L (loose): binds ADP+Pi 2. T (tight): ATP forms 3. O (open): ATP released into matrix |
|
|
ATP, ADP, and P transport
other transporters that contribute to ATP synthase to make ATP |
- phosphate translocase (symporter): brings in H2PO4, contributes P to ATP synthase
-Adenine nucleotide synthase (antiporter): contributes ADP to ATP synthase and transports ATP from matrix to intermembrane space |
|
|
2,4-dinitrophenol (DNP)
|
-Uncoupling of OP
-weak acid that picks up a proton from intermembrane space (high proton conc) and moves it across inner membrane to matrix where proton dissociates - works without using ATP synthase= ATP not being made, ETC working harder -now illegal diet drug. weight loss b/c your body is producing heat but no ATP, people die from using this *addition of this "uncoupler"= rapid increase in O2 consumption is observed in O2 consumption curve (steep drop). could possibly help if rotenone or antimycin A were preventing O2 consumption |
|
|
Thermogenesis
|
-uncoupling of OP
-in brown fat mitochondria, helpful to make extra heat in newborns -uses thermogenin= a transporter that moves H+ from IMS to matrix without use of ATP synthase to make ATP generates heat instead -same process as dinitrophenol, only use of transporter |
|
|
Oxygen Consumption Curve
|
p02 vs. time, phosphorylation: oxidation ratio
*rate of electron transport can be measured monitoring oxygen consumption -P:O ratio depends on entry point of ETC (complex I or II): number of ATP molecules formed during the transfer of 2 electrons through whole ETC P:O ratio is -3 for electron pairs entering complex I (NADH) -2 for electron pairs entering complex II (FADH2) -1 for reduced cytochrome c -top of curve shows pO2 at time zero when mitochondria have Pi and oxidizable substrate like malate, pyruvate, and succinate available -Addition of ADP stimulates oxygen uptake (sharp drop in curve b/c O2 uptake) ADP is exhausted when Oxygen consumption stops -plataeu in curve: means oxygen not being consumed. Bad news, occurs when ADP is depleted |
|
|
Inhibitors of oxidative metabolism:
Rotenone |
-insecticide that inhibits complex I
-we can add succinate to continue ATP synthesis and oxygen consumption through complex II |
|
|
Inhibitors of oxidative metabolism:
Antimycin A |
-inhibits complex III
-addition of succinate has no effect -addition of ascorbate= donates electrons/reduced cyt c -complex IV can function normally -restores ATP synthesis and Oxygen consumption |
|
|
Inhibitors of oxidative metabolism:
cyanide, azide, and carbon monoxide Clinical correlation: cyanide poisoning |
-inhibit complex IV by binding to heme A3
-**CO binds to reduced (Fe2+) heme competitively with O2 and prevents electron transfer to O2. -**Cyanide and Azide bind to oxidized (Fe3+) heme: prevent transfer of electrons from heme a to the binuclear center -addition of succinate, ascorbate, or DNP has no affect -rapid cell death b/c they cannot make ATP -lactic acidosis occurs as a result of anaerobic metabolism -CC: rapid and extensive inhibition of ETC at the cyt oxidase step -antidote if diagnosed rapidly: nitrites that convert oxyhemoblobin (Fe2+) to methemoglobin (Fe3+) by oxidizing Fe2+ of hemoglobin to Fe3+. The methemoglibin competes with cyt a and binds some of the cyanide. -Thiosulfate causes the cyanide to react with rhodanese to form a nontoxic thiocynate. |
|
|
Total ATP yield per glucose
|
Ideal: 36-38 ATP
Actual: 30-32 ATP -due to shuttling of cytosolic NADH into mitochondria and inefficiencies of molecular mechanisms of biological systems |
|
|
Source of oxygen in ETC and OP
|
Oxygen carried from hemoglobin
-used to make ATP AND to generate heat (maintainance of body temp) |
