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26 Cards in this Set

  • Front
  • Back

What complexes in the ETC pump protons?

I, III, IV

What is the inner and outer mito membrane permeable to?

outer - permeable to small molecules


inner - impermeable (except O2, CO2, NH3, H2O)

What are the complexes and their names?

I - NADH dehydrogenase


II - succinate dehydrogenase


CoQ - Q10 or ubiquinone


III - cyt-bc1


cyt-c


IV - cyt c oxidase

FADH2 can come from where through complex II?

-TCA


-FA oxidation (fatty acyl-CoA DH- matrix


-Mito G3P DH of glycerol- intermembrane space

Describe structure of ATP synthase

f1 - in matrix (rotational energy allows synthesis of ATP)


f0 - inner membrane contains proton pore

Where does ADP come from?

ADP/ATP antiport - pump ADP into matrix so can enter synthase (driving force is protons so don't wastefully put ADP into matrix)

What happens to the ETC during hypoxia?

hypoxia--> decreased ETC --> decreased ATP --> Increased Na+ --> cell swelling --> increased plasma membrane permeability




decreased ATP/cell swelling/increased permeability --> increased Ca (mito permeability -- cell death)

What is atractyloside?

Inhibits ATP/ADP antiporter - can't get ADP in matrix and ATP in intermembrane space -->




stops ATP synthesis and ETC (bc of buildup of proton gradient)

Amytal

-barbiturate


-treatment for anxiety, epilepsy, insomnia


-reversible inhibitor of NADH DH


-protect cardiac muscle during ischemia by limiting ROS

Rotenone

-naturally occurring pesticide (aka fish poison)


-potent inhibitor of NADH DH


-no NADH can be oxidized, but succinate can enter leading to reduced ATP production

Antimycin/antifungal (agriculture)

-inhibitor of complex III - binds tightly to cyt b in reduced state


-I, CoQ, II fully reduced


-Cyt c, IV fully oxidized


-no ATP - stops ETC

CN-

-binds to oxidized form of heme iron (ferric state) of cyt oxidase a3 --> complex IV cannot be reduced


-no ATP - cell death



How do you treat CN- poisoning?

Nitrate followed by thiosulfate treatment


-nitrate converts Hb iron to ferric--> MetHb (high affinity for CN-)


-add thiosulfate and enzyme rhodanese --> SCN- + SO3 (hydrophillic - excreted)

Carbon Monoxide

-competes with O2 for binding to reduced heme-a3 in complex IV (Fe2+ form)


-more poisoning thru CO by also Hb binding

Oligomycin

-binds to F0 portion - blocks proton pathway and prevents reentry of protons into matrix


-no ATP and proton gradient builds up

What occurs as a result of uncouplers / reduction of proton gradient?

-respiratory rate is fast (no longer controlled by ADP/ATP)


-rate of respiration is limited only by availability of NADH, succinate, and O2


-acceleration of TCA and electron transfer to O2


-inhibition of ATP synthase


-generation of heat due to flow of protons into matrix

AraC, AZT

-AraC (chemo) and AZT (HIV) - uncoupler by causing membrane damage to dissipate gradient

DNP, aspirin

-uncouplers


-very lipophillic and weak bases - grab proton within intermembrane space and carry it to matrix - dissipating gradient

Thermogenin / UCP-1

-uncoupler - proton channel -found in BAT of humans/hibernating animals + newborns


-adults --> homeostasis


-newborns --> exclusively heat generation

BAT vs WAT

BAT- thermogenic, many mito, vascularized, UCP-1


WAT - non-therm, few mito/capillaries, leptin

What increases UCP1 expression?

-cold


-SNS


-fatty acids within BAT activate UCP

Where is the malate-aspartate shuttle used?

-heart, kidney, liver


-transports cytoplasmic NADH into matrix


-ONLY works if (NADH/NAD+) is higher in cytoplasm than matrix


-reversible


-1 NADH --> 3 ATP

Describe malate-aspartate shuttle

1. NADH made in cytosol --> give 2e- to oxaloacetate to make malate (via cytoplasmic malate DH)


2. Malate gets into matrix


3. In matrix, malate gives 2e- to NAD+ --> NADH and oxaloacetate (via mito malate DH)


4. recycle oxaloacetate --> alpha-KG (via AST)


5. alpha-KG crosses into cytosol and becomes oxaloacetate via AST

How is oxaloacetate --> alpha-KG?

-oxaloacetate + glutamate (via AST) --> aspartate + alpha-KG

Where is the glycerol phosphate shuttle used?

-skeletal muscle, brain --> don't want to depend on conc gradient/run all the time


-irreversible


-1 NADH --> 2 ATP via FADH2


-can be used under all conditions

Describe glycerophosphate shuttle

1. NADH in cytosol gives electrons to DHAP --> glycerol 3-P


2. goes to glycerol 3-P DH --> makes FADH2 and DHAP


3. FADH2 goes directly to CoQ of ETC