BC 28 ETC and OP

Question 1

mitochondrial structure

Answer 1

outer membrane: OMM: Porous, permeable to most ions and small molecues

IMM: impermeable to most ions and mols, forms the cristae: increase SA, 75% protein, low chol

IMS: compartments for reactions, allows for ion proton gradients that power ATP production’

Matrix: highly concentrated mix of proteins and enzymes
-urea, heme, mtDNA rep, ribosomes, mutiples copies mtDNA

Question 2

location of ETC

Answer 2

Running on the IMM

• fed from TCA in Matrix
• compled II (Succinate Dehydrogenase) is the same enzyme as step 6 of the TCA cycle (makes FADH2 for entry to ETC)

ALWAYS RUNNING

Question 3

components of ETC

Answer 3

Complex I II III IV
complex V is ATP Synthase

-almost 100% respired O2 consumed by Complex IV donating e to O2 creating 2H2O

Question 4

Functioning ETC

Answer 4

CI-receives e- from NADH, transferring H+ to IMS

CII receives e from FADH2
-not trans mem protein

Ub Ubiquinone (in membrane) receives e’s from CI and CII and transfers it to CIII

CIII-receives e’s from Ub(H+ sent to IMS) donating e to cytochrome C (free in IMS)

Cytochrome C transports e and donates it to CIV

• CIV reduces O2 to create 2H2O
• H+ sent to IMS

Question 5

relevance of Ox/Red Reactions in ETC Complexes

Answer 5

Sending H+ into IMS (CI CIII CIV) creates electrochemical proton concentration gradient aka mitochondrial membrane potential

-CV (atp synthase) creates ATP from ADP + Pi

Question 6

Regulation of ETC

Answer 6

Complex IV is allosterically inhibited by ATP (so full complex only slowed down)

• primary regulation of the Energy state, similar to TCA
• addnl regulation based on substrate availability (nadH FADH2 O2)
• basically it runs in every state just at different speeds

Question 7

Oxidative Phosphorylation

Answer 7

since ETC I-IV and V are strongly coupled the entire reaction is oxidative phosphorylation
-inhibiting e- flow nearly IMMEDIATE inhibition of ATP synthase and vice versa

Question 8

ETC Inhibitors

Answer 8

act: binding to a complex to prevent redox

CN- (Cyanide): binds to Ferric Iron (Fe3+) almost exclusively in CIV (also small amounts in MetHb)

CO (carbon monoxide) binds to Ferrous Iron (Fe2+) in hemoglobin as well as CIV

• many others
• decreased O2 NADH FADH2 consumption and decreased ATP synthesis

Question 9

Uncoupler

Answer 9

uncouple oxidative phosphorylation

• ETC without ATP
• increase O2 NADH FADH2 consumption
• decrease ATP synthesis
• increase rate of redox, increase HEAT

UCP: uncoupling proteins: in BROWN FAT cells (newborns) packed with mitochondria, cytochromes look brown. (and hibernation)

Chemical uncouplers: DNP2,4 (gramidicin,valinomycin)

• DNP crosses OMM with ease
• binds to OH, neutralizing neg charge
• crosses IMM
• dissociates and becomes trapped

-increase fever and hyperthermia

Question 10

Transport across imp IMM

Answer 10

Requires assistance

Proton Gradient:

• Pyruvate Symport
• Pi Symport

Voltage Gradient:
-ADP ATP antiport exchange
-ADP3- into matrix
-ATP4- out of matrix
both of these pass easily across the OMM

Question 11

What happens when Glycolysis and ETC needs met? Priority 1

Answer 11

accumulation of the following four substrates that lead to the following paths

1. ATP
   - ETC inhibition
2. NADH and FADH2
   - TCA decreased
3. Citrate
   - decreased TCA
   - OVERFLOW OF CITRATE
   - -used for FA synthesis
   - -inhibits PFK1 (inhibiting glycolysis)
   - eventually leads to increased citrate synthase
4. AcCoA
   - inhibits PDHC
   - activates Pyruvate Carblxylase
   - -converts Pyruvate to OAA
   - –used to prime TCA
   - –or gluconeogenesis