Mitochondrial Bioenergetics (TCA And OxPhos)

Question 1

The TCA cycle is ___________, meaning it involves both catabolic and anabolic processes

Answer 1

Amphibolic

Question 2

In order for the TCA and oxphos to occur, pyruvate must get into the mitochondria. How does it do this?

Answer 2

Mitochondrial pyruvate carrier (MPC)

Question 3

What enzyme is responsible for the decarboxylation of pyruvate?

Answer 3

PDH (pyruvate dehydrogenase) complex

Question 4

PDH is a holoenzyme composed for 3 separate enzymes, what are they?

Answer 4

E1 = pyruvate decarboxylase
E2 = dihydrolipoyl transacetylase
E3 = dihydrolipoyl dehydrogenase

Question 5

Do the following act as activators or inhibitors of PDH:

Ca++
Mg++
CoA
NAD

Answer 5

Activators

Question 6

Do the following act as activators or inhibitors of PDH:

NADH
Arsenite

Answer 6

Inhibitors

Question 7

The overall reaction of the PDH complex is:

Pyruvate + NAD+ + ________ ——> Acetyl CoA + _______ + NADH + _______

Answer 7

CoA

CO2; H+

Question 8

What is the purpose of pyruvate dehydrogenase phosphatase?

Answer 8

Activates PDH (so active form is DEphosphorylated!)

[note that PDH kinase deactivates PDH by adding a phosphate]

Question 9

What would be the clinical result of patients who are PDH phosphatase deficient?

Answer 9

PDH would be constitutively phosphorylated, and thus inactive, meaning that glucose becomes lactate instead of acetyl CoA

The ultimate result is lactic acidosis which primarily affects the CNS

Question 10

What are the 3 most regulated steps of TCA?

Answer 10

Acetyl CoA –> Citrate (citrate synthase)

Isocitrate –> alpha-ketoglutarate (isocitrate dehydrogenase)

Alpha-ketoglutarate –> succinyl CoA (alpha-ketoglutarate dehydrogenase)

Question 11

____________ reactions act to replenish intermediates for the TCA cycle

Answer 11

Anaplerotic

Question 12

What are the 2 major anaplerotic reactions?

Answer 12

Degradation of amino acids

Carboxylation of pyruvate

Question 13

What classic disorder of the TCA cycle consists of global developmental delay, severe neurological problems, metabolic acidosis, severe microcephaly, and mental retardation?

Answer 13

2-oxoglutaric aciduria

Question 14

What classic disorder of the TCA cycle consists of neurological impairment, encephalomyopathy, dystonia, increased urinary excretion of fumarate, succinate, alpha-ketoglutarate, and citrate?

Answer 14

Fumarase deficiency

Question 15

What recently discovered disorder of the TCA cycle is associated with mutations of 2/3 subunits making up the enzyme - including SUCLA2 and SUCLG1

Answer 15

Succinyl CoA Synthetase Deficiency

Question 16

What recently discovered disorder of the TCA cycle consists of profound hypotonia, progressive dystonia, muscular atrophy, and severe sensorineural hearing impairment?

Answer 16

Mitochondrial Depletion Syndrome

Question 17

What is the site of most of the TCA cycle and fatty acid oxidation?

Answer 17

Matrix of mitochondria

Question 18

All TCA enzymes are located in the mitochondrial matrix except which one?

Answer 18

Succinate dehydrogenase

Question 19

What is the baseline pH in the mitochondrial matrix?

Answer 19

High (low H+ concentration)

Question 20

Mitochondria continually undergo the processes of __________ and _________ to affect processes like Mt DNA stability, respiratory capacity, apoptosis, response to cellular stress, and mitophagy

Answer 20

Fusion

Fission

Question 21

What are the 2 types of redox reactions?

Answer 21

The electron-only transfer (electrons are transferred between 2 metal ions - note that the oxidant is always on the side of the reaction with the electrons)

The reducing-equivalent transfer (transfer of a proton and an electron)

Question 22

What does E0’ stand for?

Answer 22

It is the standard redox potential - which is a measure of the affinity of a redox pair of electrons. A lower E0’ = a lower affinity

Question 23

Oxidative phosphorylation involves the creation of a proton gradient by pumping protons across the mitochondrial membrane, thus ____________ the pH in the intermembrane space

Answer 23

Decreasing (adding H+ makes it more acidic)

Question 24

How does E0’ (standard redox potential) relate to dG0’?

Answer 24

They are inversely related

Question 25

What is the chemiosmotic hypothesis?

Answer 25

ATP synthesis in respiring cells comes from the electrochemical gradient across the inner mitochondrial membrane by using the energy of NADH and FADH2 formed from the breaking down of energy rich molecules

Question 26

What enzyme catalyzes the synthesis of ATP, and what drug is capable of inhibiting it?

Answer 26

ATP synthase

Can be inhibited by Oligomycin, which disrupts proton transport through the channel so the gradient cannot be created (may result in lactate accumulating in blood and urine)

Question 27

What 2 factors is Oxphos most sensitive to in terms of overall regulation?

Answer 27

Presence of molecular oxygen

ATP/ADP ratio

Question 28

What is “uncoupling” in OxPhos, and in what situations is it useful?

Answer 28

Electron transfer becomes uncoupled from the proton gradient, so protons re-enter the mitochondrial matrix from the intermembrane space and, instead of ATP, heat is generated

Useful for hibernating animals and newborn babies

Question 29

Which of the following most accurately describes mitochondrial transport systems?

A. Symporters
B. Uniporters
C. Antiporters
D. Diporters

Answer 29

C. Antiporters

Question 30

Antiporters are necessary in the mitochondrial membrane because reduced ______ cannot cross without them

Answer 30

NADH

Question 31

What are the 2 shuttle systems associated with mitochondrial transport systems?

Answer 31

Malate-aspartate shuttle

Glycerophosphate shuttle

Question 32

The malate aspartate shuttle operates in the ________, liver, and _________.

It generates NADH in the ___________, and NADH enters the ETC at complex ____

Answer 32

Heart; kidneys

Mt. matrix; 1

Question 33

The glycerophosphate shuttle operates in the ________ and muscle.

It generates _________ in the inner mt. membrane, which then joins the ETC at ________

Answer 33

Brain

FADH2; CoQ

Question 34

What was the first diagnosed mitochondrial disease?

Answer 34

Luft’s disease

Question 35

What are the 2 primary causes of mitochondrial disease?

Answer 35

Defect in nuclear DNA encoding mitochondrial proteins

Defect in mitochondrial DNA

Question 36

What are some secondary causes of mitochondrial disease?

Answer 36

Ischemia
Reperfusion
Cardiovascular disease
Renal failure
Drugs and aging
Alcohol
Smoking