Lecture 6 - Oxidative phosphorylation and Mitochondrial Function

Question 1

What are the two glycolytic enzymes that perform substrate level phosphorylation?

Answer 1

1) Phosphoglycerate kinase

2) Pyruvate kinase

Question 2

Cause & symptoms of pellagra

Answer 2

Cause: Niacin (B3) deficiency
Symptoms: Dermatitis, dementia, diarrhea (3Ds for B3)

Question 3

What does NADH accept when reduced?

Answer 3

2e- and H+

a hydride

Question 4

What does FADH2 accept when reduced?

Answer 4

2 e- and H+

Question 5

List the complexes of the electron transport system.

Answer 5

1) NADH Dehydrogenase
2) Succinate-Q reductase
3) Cytochrome bc1 complex (complex III)
4) Cytochrome c oxidase (complex IV)

Mobile carriers:
CoQ (carries 2e-, 2H+), Cytochrome C (1e-)

Question 6

Protein molecules that contain heme with an iron atom

Answer 6

Cytochromes (1e- carriers that are fixed)

Question 7

Proteins that contain Fe and S in a cluster

Answer 7

Fe-S, 2Fe-2S, 4Fe-4s (1e- carriers that are fixed)

Question 8

Copper containing cytochrome

Answer 8

Cytochrome C oxidase (1e- carriers that are fixed)

Question 9

How many Protons must pass through ATP synthase to produce an ATP?

Answer 9

4

Question 10

How many protons are pumped into the inter membrane space by each ETC complex.

Answer 10

1) Complex I (NADH DH) - 4
2) Complex II (Succinate DH) - 0
3) Complex III (Cytochrome b-c1 complex) - 4
4) Complex IV (Cytochrome c oxidase) - 2

Question 11

What agents inhibit complex I?

Answer 11

Rotenone and amytal

Question 12

What agents inhibit complex III?

Answer 12

Antimycin A

Question 13

What agents inhibit complex IV?

Answer 13

CN-, N3-, CO

Question 14

What is the primary indicator of prolonged defects in oxidative phosphorylation?

Answer 14

Lactate accumulation

Question 15

What is the significant of dinitrophenol?

Answer 15

It is an uncoupler of electron transport. It is lipophilic and can pass back and fourth between the matrix and inter membrane space, shuttling protons down their gradient and back into the matrix. This is bad!

Question 16

UCP1

Answer 16

Uncoupling protein one (thermogenin) is a channel that inserts in the inner membrane of the mitochondria and allows protons to flow back down their gradient into the matrix.

Question 17

LOHN (symptoms and cause)

Answer 17

Symptoms: Bilateral subacute optic neuropathy (blindness) effects men but not women. Cause: Mt DNA mutation in complex I - 95% of cases)

Question 18

MELAS (symtoms and cause)

Answer 18

Symptoms: Mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes. Cause: mt DNA mutation in tRNA Leu - 80%)

Question 19

Leigh syndrome (symptoms and cause)

Answer 19

Symptoms: Developmental delay, ataxia, blindness, seizures, lactic acidosis Cause: mt DNA and nuclear genes required for electron transport or PDH complex.

Question 20

MERRF (symptoms and cause)

Answer 20

Symptoms: Myoclonic epilepsy with ragged red fibers (myopathy, ataxia, blindness). Cause: mt tRNA Lys