BIOL 288 - Metabolism - Pyruvate Oxidation

Outer Mitochondrial membrane (OMM)

permiable

porins - allows for free movment of small molecules between the cytoplasm and the intermembrane space

inner mitocondrial membrane (IMM)

impermiable

seperates the inter membrane space from the matrix

contains ETC and F-type pumps

how does pyruvate get into the matrix

crosses OMM via porin VADC (voltage dependent anion channel)

crosses IMM via MPC (mitocondrial pyruvate carrier)

• H+/puruvte symporter (pyruvate against gradient)

pyruvate oxidation (per glucaose) summery

2 pyruvate + 2 CoA + 2 NAD+ —> 2 acetyl CoA + 2 NADH + 2 CO2

how does pyruvate get to Acetyl CoA

pyruvate loses C to CO2 and is oxidixed to acetyl CoA

froms high energy thioester bond with S-CoA

products of pyruvate Oxidation

2 acetyl CoA, 2 NADH, CO2

first step of CAC

reaction is fueled by the breaking of the thioester bond

actetal CoA (2C) enters the cycle and joins oxaloacetate (4C) the make citrate (6C)

how many decarboxylations and oxidations in CAC

2 decarboxlations (loss of 2 CO2)

4 oxidations (3 with NAD+ and 1 with FAD)

what does GTP make in CAC

1 ATP in CAC

what completes one turn of the the CAC

the regaeneration of oxaloactate

CAC summery per cycle

3 NADH, 1 FADH2, 1ATP, 2 CO2

CAC summery per glucose

(2 turns of the cycle)

6 NADH, 2 FADH2, 2ATP, 4 CO2

electron affinity

Enot’

the more negative Enot’ means

better electron donor (best reducer)

more postive Enot’ means

better electron acceptor (best oxidizer)

a pair can only donate electrons to the reaction (more negative or more psotive)

more positve

5 electron carriers of ETC

1. Flavoprotiens

2. Iron-sulfur protiens

3. Cytochromes

4. Three copper atoms

5. Coenzyme Q

Flavoproteins

can transfer 2 e- and 2H+

ex) NADH dehydrogenase

Iron-sulfur Protiens

can transfer 1e- and no H+

Cytochromes

can transfer 1 e- and no H+

5 different cytochromes in ETC (a, a3, b,c1,c)

Three copper Atoms

can transfer 1e- and no H+

Coenzyme Q

can transfer 2e- and 2 H+

lipid soluable, floats freely int mitochondiral membrane

oragnization of electron carriers

2e- from NADH —> complex 1 —> CoQ —> 3 —> cyt c —> 4 —> oxidase

2e- from Succinate —> complex 2 —> CoQ

Complex 1: NADH dehydrogenase

e- doner: NADH

last e- acceptor: CoQ

4H+ pumped into intermembrane space

Complex 3: cytochrome bc1

e- doner: CoQ

last e- acceptor: cyto c

4 H+ pumped out of matrix into IMS

complex 4: cytochrome c Oxidase

e- doner: cyto c

last e- acceptor: O2

O2 picks up 2H+ from the matrix

Complex 2: Succinate Dehydrogenase

e- doner: succinate

last e- acceptor: CoQ

does not pump H+

ETC and H+ pumping productes

10H+ per NADH

6H+ per FADH2

2 malate transporters

1. Malate-aspartate shuttle

2. Glycerol-phosphate shuttle

1. Malate-aspartate shuttle

• NADH enters at complex 1

• Pump 10H+

20H+ total

Glycerol-phosphate shuttle

FADH2 enters at complex 3

6H+ pumped

12H+ total

mechinism of raotation in c ring of ATP-ase

1. moves down the gradient and into the emtpy site in half channel 1

2. H+ displaces the +arg which swings to the ajeactet filled binding site displaceing other H+

3. other H+ moves into half channel 2 and relases to the matirx

4. c-ring rotates counter-cockwise

5. repaets with new H+

binding change model for ATP-ase

O: relase ATP, ADP + Pi enter

L: ADP +Pi loosly bound

T: ADP + Pi tightly bound (ATP synthesis)

360° rotation of ATP-ase prouduces how many ATP

3 ATP

rotates clockwise in 120° incements

total ATP produced per 1 glucose

42.5 ATP (GP shuttle) or 45.5 ATP (MA shuttle)

Consequences of DNP

acts as a proton shuttle that disruptes the H+ gradient

1. decreased ATP synthesis

2. H+ gradenet potential energy dispates as heat (instead of ATP)

3. constant demand of O2 (increased breathing)

4. relase of mitochondrial Ca2+ stores (musle regititly)