Terminal respiration

Question 1

Describe the function of the electron transport chain

Answer 1

• Energy rich molecules, such as glucose, are metabolised by a series of oxidation reactions ultimately yielding CO2 and water
• The metabolic intermediates of these reactions donate electrons to specific coenzymes – nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) – to form the energy rich reduced coenzymes NADH and FADH2
• These reduced coenzymes can, in turn, each donate a pair of electrons to a specialized set of energy carriers, collectively called the electron transport chain

Question 2

Describe the process of the electron transport chain

Answer 2

Step 1 - NADH-Q oxidoreductase
- Oxidises NADH and passes e- to ubiquinone to make ubiquinol, pumps H+ into intermembrane space

Step 2 - succinate Q reductase
- Oxidises FADH2 and passes e- to ubiquinone to make ubiquinol

Ubiquinone/ubiquinol complex

Step 3 - Q - Cytochrome c oxidoreductase
- Takes ubiquinol and reduces it to cytochrome c. Also takes e- from other ubiquinol and passes these to cytochrome c

Step 4 - Cytochrome C oxidase
- Takes e- from cytochrome c and passes them to molecular O2. e- channeled through Fe-Ce centre and enzyme pumps protons into intermembrane space

H proton gradient stores energy

Question 3

Describe how the proton concentration gradient is used to convert ADP to ATP. 


Answer 3

Utilised by ATP synthase

• Protons eventually flow down their concentration gradient, back into the matrix of the mitochondria
• Only a relatively small number of sites exist on the membrane were this happens
• At these sites a large multi-unit protein complex called ATP synthase (ATPase for short) is found
• ATPase has a mechanism that allows protons to pass through
• As they flow through ATPase, the energy stored in the gradient is used to convert ADP + Pi to ATP
• ATP then takes this potential energy to do work in the cells of the body
• This is the final step in metabolising the food molecules we eat into energy

Question 4

What is the glycerol phosphate shuttle?

Answer 4

• For oxidation in the terminal respiratory system of eukaryotic cells, NADH and FADH2 have to be in the mitochondrial matrix
• The majority of NADH and FADH2 is formed there (citric acid cycle and β-oxidation of fatty acids), but some NADH is formed in the cytoplasm (glycolysis)
• A shuttle is used to move reducing equivalents across the mitochondrial membrane
• Cytoplasmic NADH cannot cross the membrane, but FADH2 within the mitochondria can pick up e-’s via the
• This process is termed the glycerol phosphate shuttle

Question 5

What is the energetic price concerned with the glycerol phosphate shuttle?

Answer 5

• Oxidation of FADH2 in the electron transport chain generates, per mol, less ATP than oxidation of NADH
• Thus, an energetic ‘price’ is paid for using cytosolic reduced co-substrates in terminal respiration

Question 6

What is oxidative phosphorylation?

Answer 6

As electrons are passed through the chain, they lose much of their free energy. Part of this energy can be captured and stored by the production of ATP from ADP and inorganic phosphate (Pi). This process is called oxidative phosphorylation.

Question 7

What happens to the remaining free energy following the electron transport chain?

Answer 7

The remainder of the free energy not trapped as ATP is used to drive ancillary reactions such as Ca2+ transport into mitochondria and to generate heat.

Question 8

Describe ATP synthase

Answer 8

Has 2 parts:
o F0 – membrane bound proton conducting unit
o F1 – protrudes into the mitochondrial matrix and acts as the catalyst for ATP synthesis

Question 9

What is the stoichiometry of oxidative phosphorylation?

Answer 9

Stoichiometrically, approximately 2.5 and 1.5 mol of ATP are generated per mol of NADH and FADH2 respectively

Question 10

What is coupling and uncoupling, and what disease is caused by this?

Answer 10

• Electron transport is said to be coupled to ATP synthesis
• If the inner mitochondrial membrane becomes permeable to protons, the proton gradient cannot be generated
• If this happens the electron transport can still occur, with O2 being reduced to H2O, but no ATP is made
• The two processes are now uncoupled
• The energy released from e-’s passing along the terminal respiration system does not make ATP, and is released as heat
• Malignant hyperthermia is a disease caused by ‘leaky’ mitochondrial membranes that uncouple electron transport and ATP synthase

Question 11

What is malignant hyperthermia and what causes it?

Answer 11

• Susceptible people, exposed to halothane (or halothane-like drugs) experience a large increase in their body temperature
• 1 in 75,000 people (1:15,000 children)
• Halothane is believed to make the inner mitochondrial membranes in muscle leaky in some way and uncouple the electron transport chain from ATP synthesis
• Muscle cells will usually become irreversibly damaged from the excessive heat build up

Question 12

What is malignant hyperthermia similar to?

Answer 12

A similar thing happens in pigs
– Porcine stress syndrome
– When shipped to market they can become ‘stressed’ following halothane exposure
– Results in pork meat that is watery and very low pH (i.e., pickled)

Question 13

What is intentional uncoupling?

Answer 13

• Brown fat found in newborn infants and in other mammal species
• Brown fat cells have lots of mitochondria
• If a baby becomes cold, nor-epinephrine triggers the opening of a channel in a protein called thermogenin
• Thermogenin sits on the inner mitochondrial membrane of brown fat cells, and if uncoupled there is no generation of a H gradient and therefore high energy electrons intended for ATP synthesis instead release energy as heat

Question 14

ATPase utilises which mechanism in order to generate ATP?

Answer 14

Binding change mechanism