Exam 2 Agbas

Question 1

pyruvate –> acetyl coa (3 steps)

Answer 1

decarboxylation –> oxidation –> transfer acetyl group to coenzyme A

Question 2

pyruvate dehydrogenase regulation

Answer 2

allosteric interactions and reverse phosphorylation

• high [acetyl coa] directly inhibits E2 (doesn’t stop the cycle, just slow it down)
• NADH inhibits E3
• products of TCA cycle increase phosphorylation (inactive) of PDH E2
• ADP and pyruvate activate phosphatases

Question 3

isocitrate dehydrogenase

Answer 3

1/4 redox reaction
RATE LIMITING STEP
intermediate: oxalosuccinate
–> a ketoglutarate + NADH + CO2

Question 4

a-ketoglutarate dehydrogenase

Answer 4

similar to PDH
thioester bond = HIGH ENERGY BOND
if hydrolyzed then that energy is huge.
–> succinyl CoA + Co2 + NADH

Question 5

succinyl coA synthase

Answer 5

thioester bond!!

• *only step that directly produces GTP/ATP (substrate level phosphorylation) NOT OXPHOS
• GTP (anabolic reactions in liver)
• ATP (cellular respiration (skeletal and heart muscle)
• -> ATP/GTP + CoA

Question 6

succinate dehydrogenase

Answer 6

enzyme in inner mitochondrial membrane (associated with ETC- complex 2)
–> FADH2

Question 7

malate dehydrogenase

Answer 7

LAST STEP
malate oxidation = positive standard free energy
-specifically recognizes only L-malate (not D)
–> NADH + oxaloacetate

Question 8

TCA cycle regulation (PDH)

Answer 8

• via PDH, E2 and E3 inhibition
• energy charge of cell dictates PDH complex activity
• -if high (fed condition) –> PDH inhibited
• -if low –> PDH upregulated

Question 9

TCA cycle regulation controls (3)

Answer 9

1. citrate synthase prevents wasteful hydrolysis of acetyl coA
2. isocitrate dehydrogenase: allosterically stimulated by ADP, product: NADH
3. a ketogluturate dehydrogenase: similar to PDH
   - -if increased a-ketoglutarate –> used for AA and purine base synthesis

Question 10

TCA = anaplerotic

2 reactions

Answer 10

“fill up” - reactions provide intermediates for TCA cycle and biosynthesis pathways

1. degradation of AA
2. carboxylation of pyruvate

Question 11

which AA can enter where in TCA cycle (degradation of AA)

Answer 11

Phe/Tyr/Asp –> fumarate
Asn/Asp –> oxaloacetate
Gln/Pro/His/Arg/glutamate –> a-ketoglutarate
Thr/Met/Ile/Val –> succinyl coA

Question 12

T/F: TCA cycle can shut down

Answer 12

false; only slows down. but never shuts down

Question 13

mitochondria structure

Answer 13

2 membrane: outer and inner
–outer: permeable due to porin presence (VDAC)
–inner: impermeable, metabolite transports (more selective), where OXPHOS occurs
2 compartment: intermembrane space and matrix
–matrix: TCA cycle and FA oxidation

Question 14

Oxphos goals (3)

Answer 14

1. transfer e from NADH/FADH2 –> O2 (e- flow is exergonic!)
2. establish proton gradient across inner mito membrane
3. ATP synthesis

Question 15

Complex 1

Answer 15

NADH Q oxidoreductase

Question 16

Complex 2

Answer 16

succinate Q reductase

AKA CoQ

Question 17

complex 3

Answer 17

Q cytochrome c oxidoreductase

Question 18

complex 4

Answer 18

cytochrome c oxidase

Question 19

respirasome = (3)

Answer 19

complex 1,3,4

Question 20

energies of ETC

Answer 20

highest free energy: complex 1
lowest free energy: complex 4
lowest standard redox potential: complex 1 (-0.32V)
highest standard redox potential: complex 4 (+0.82V)

Question 21

transfer of electrons (oxphos)

Answer 21

flow from lower Eo’ to higher Eo’
Eo’ inversely related to Go’
deltaGo’ = -nFdeltaEo’

Question 22

establishing proton gradient

Answer 22

when e- move, then H+ move from matrix (-) to intermembrane space (+)

Question 23

pmf (proton motive force)

Answer 23

• *need both to function**
  1. ph gradient
  2. membrane potential
• if its leaky or membrane disrupted then no PMF and ATP synthesis does not occur!!

Question 24

chemiosmotic hypothesis/theory (3)

Answer 24

1. ETC moves H+ as e- flow from one complex to next
2. ATP synthase uses pmf to make ATP via ADP
3. inner mitochondrial membrane is impermeableto H+ and OH ions. so need the complexes.

Question 25

ATP synthase structure

Answer 25

aka complex 5
in inner membrane
-F0 subunit: in membrane with proton channel
-F1 subunit: protrudes into matrix, contains catalytic domain
^^^ need both for ATP production

Question 26

ATP synthase information

Answer 26

-molecules form dimers –> oligomers
-stabilize individual molecules to rotational forces required for catalysis
-maintains curvature in inner membrane
-cristae allow proton gradient to be close to ATP synthase!!!!
1 mol ATP = 4 H+ to pass through

Question 27

inhibitor of ATP synthase

Answer 27

oligomycin - disrupts proton transport through channel from space to matrix.

Question 28

T/F: NADH is able to enter the mitochondria

Answer 28

False; uses two shuttles;
malate-aspartate shuttle
glycerophosphate shuttle

Question 29

malate-aspartate shuttle

Answer 29

in heart, liver, kidney

generates NADH into matrix –> NADH enters ETC at complex 1

Question 30

glycerophosphate shuttle

Answer 30

in skeletal m and brain
generates FADH2 in inner mitochondrial membrane
FADH2 joints ETC at complex 2 (CoQ)

Question 31

inhibition of oxphos (3)

Answer 31

when transfer of e- inhibited…..

• decrease in pumping protons
• decrease in protein gradient
• inhibition of ATP synthesis

Question 32

thermogenesis in brown adipose tissue

Answer 32

coupling = oxphos = normal ATP synthesis

uncoupling = proton leak = heat generation and decrease body’s metabolism