BCHM - Bioenergetics

Question 1

Where does the TCA cycle take place?

Answer 1

Inside the mitochondria

Question 2

What is the common pathway into the TCA cycle?

Answer 2

Fats, polysaccharides, and proteins are converted into Acetyl-CoA before they can enter the TCA cycle and be used for energy.

Question 3

What are the 3 energy equivalent substances generated via the TCA cycle?

Answer 3

NADH, FADH2, and GTP

Question 4

Describe how Acetyl-CoA is derived from carbohydrates.

Answer 4

Glucose (6 carbons), gets oxidized during glycolysis into 2 pyruvates (3 carbons). The 2 pyruvates are then decarboxylated into 2 Acetyl Co-A molecules for TCA cycle use

Question 5

Describe how Acetyl CoA is derived from lipids.

Answer 5

Triacylglycerols are converted into fatty acids. The fatty acids then undergo beta-oxidation to form Acetyl CoA

The oxidation of ketone bodies also forms Acetyl CoA

Question 6

Describe how Acetyl CoA is derived from proteins.

Answer 6

Proteins are broken down into amino acids. The amino acids are then turned into Acetyl CoA

Question 7

What does PDC stand for?

Answer 7

Pyruvate dehydrogenase complex

Question 8

When PDC is phosphorylated, is it in its active or inactive form?

Answer 8

Phospho = INACTIVE
Dephospho = ACTIVE

Question 9

Where in the PDC does phosphorylation occur?

Answer 9

Phosphorylation occurs in coenzyme Thiamine pyrophosphate (TPP) of the E1 complex

Question 10

The PDC is made up of E1, E2, and E3 subunits. What are each of the subunits comprised of?

Answer 10

E1 = TPP
E2 - Lipoic acid and CoA
E3 = NAD+ and FAD

Question 11

What enzyme ACTIVATES the PDC?

Answer 11

Pyruvate dehydrogenase phosphatase (PDP)

Question 12

What are the activators of pyruvate dehydrogenase phosphotase, and thus activate the PDC?

Answer 12

Ca2+ and Mg2+ activate PDP

Question 13

What acts as inhibitory signals of the active state E1 subunit of the PDC?

Answer 13

Acetyl CoA and NADH

Question 14

What molecules inhibit the deactivation of the PDC?

Answer 14

Pyruvate, CoA, NAD+, and ADP

Question 15

What molecules cause the deactivation of pyruvate dehydrogenase kinase?

Answer 15

Acetyl CoA, NADH, and ATP

Question 16

What enzyme changes PDC from being active to inactive?

Answer 16

Pyruvate dehydrogenase kinase (PDK)

Question 17

In a phosphate deficiency, what happens to the PDC?

Answer 17

It remains phosphorylated, aka inactive. This leads to glucose being converted to lactate instead of Acetyl CoA

Buildup of lactate causes lactic acidosis, resulting in CNS effects

Question 18

With a phosphate deficiency, what amino acid should be avoided?

Answer 18

Alanine should be avoided and a ketogenic diet is strongly recommended

Question 19

In what steps of the TCA cycle is NADH produced?

Answer 19

Isocitrate to alpha-ketoglutarate (isocitrate dehydrogenase)

Alpha-ketoglutarate to Succinyl-CoA (alpha-ketoglutarate dehydrogenase)

Malate to oxaloacetate (malate dehydrogenase)

TOTAL OF THREE NADH PRODUCED EACH CYCLE

Question 20

In what step of the TCA cycle is GTP produced?

Answer 20

Succinyl-CoA to Succinate (Succinyl-CoA dehydrogenase)

Question 21

In what step of the TCA cycle is FADH2 produced?

Answer 21

Succinate to fumarate (succinate dehydrogenase)

Question 22

How many ATP are produced by each NADH, FADH2, and GTP?

Answer 22

NADH = 2.5 ATP
FADH2 = 1.5 ATP
GTP = 1 ATP

Question 23

What is the rate limiting step of the TCA cycle?

Answer 23

Isocitrate to alpha-ketoglutarate via the enzyme isocitrate dehydrogenase

Question 24

What is the function of the pyruvate dehydrogenase complex?

Answer 24

Convert Pyruvate into Acetyl-CoA for entrance into the TCA cycle

Question 25

Acetyl CoA combines with what molecule to form citrate?

Answer 25

Oxaloacetate generated via the TCA cycle

Question 26

When cellular levels of ATP are low, what happens to the TCA cycle?

Answer 26

Increased activity of TCA cycle to produce more ATP

Question 26

When cellular levels of ATP are low, what happens to the TCA cycle?

Answer 26

Increased activity of TCA cycle to produce more ATP

Question 27

What are the two major anaplerotic reactions in the TCA cycle?

Answer 27

Degradation of amino acids and carboxylation of pyruvate

Question 28

What amino acids are degraded to replenish alpha-ketoglutarate? (5 of them)

Answer 28

Glutamine, proline, histidine, arginine, and glutamate

Question 29

What amino acids degrade to form Succinyl CoA in the TCA cycle? (4 of them)

Answer 29

Threonine, methionine, isoleucine, and valine The metabolic byproducts for propionyl CoA, which then replenishes Succinyl CoA

Question 30

What amino acids are degraded to form fumarate in the TCA cycle? (3 of them)

Answer 30

Phenylalanine, tyrosine, and aspartate

Question 31

What amino acids are degraded to form oxaloacetate in the TCA cycle? (2 of them)

Answer 31

Asparagine and aspartate

Question 32

Describe 2-Oxoglutaric aciduria (Alpha-ketoglutaric acid)

Answer 32

Rare disorder displaying developmental delay and severe neurologic problems in infants including metabolic acidosis, microcephaly, and intellectual disability

Question 33

Describe Fumarase deficiency

Answer 33

Severe neurological impairment. Fatal outcome within first 2 years of life Encephalomyopathy, dystonia, urinary excretion of TCA intermediates are common

Question 34

What three key goals must be accomplished for a successful OxPhos?

Answer 34

1. transfer of electrons from NADH and FADH2 to O2 2. establish proton gradient across INNER membrane and intermembrane space 3. Synthesize ATP

Question 35

In the TCA cycle, the first goal is the transfer of electrons. Describe how this happens

Answer 35

Electrons flow from molecules with low Standard Redox Potential to those with the highest.

Question 36

What causes the pumping of H+ through the mitochondrial inner membrane?

Answer 36

Electron transfer through the respiratory chain.

Question 37

What two factors constitute a proton-motive force (pmf) to drive ATP synthesis by Complex V?

Answer 37

1. pH gradient | 2. membrane potential

Question 38

How many H+ molecules are required to form 1 ATP via the ATP Synthase (Complex V)?

Answer 38

4 H+ required to form 1 ATP via Complex V

Question 39

What molecule inhibits proton transport through Complex V?

Answer 39

Oligomycin

Question 40

What inhibits Complex I?

Answer 40

Amytal, Rotenone, Myxothiazol, and Piericidin A ARM Pit

Question 41

What inhibits Complex II?

Answer 41

Malonate

Question 42

What inhibits Complex III?

Answer 42

Antimycin

Question 43

What inhibits Complex IV?

Answer 43

CO, Cyanide, and H2S

Question 44

What inhibits Complex V?

Answer 44

Oligomycin

Question 45

What inhibits Complex V?

Answer 45

Oligomycin

Question 46

A high ATP/ADP ratio will do what?

Answer 46

Decrease ATP concentrations

Question 47

A low ATP/ADP ratio will do what?

Answer 47

Increase ATP concentration

Question 48

What occurs during uncoupling in OxPhos?

Answer 48

Protons uncouple from their carrier electrons and reenter the mitochondrial matrix. The TCA cycle is accelerated and ATP synthase is inhibited (no ATP synthesis). There is heat generation

Question 49

What are the two mechanisms of action for Superoxide Dismutase?

Answer 49

1. Cu/Zn SOD (SOD1) - cytosolic | 2. Mn/Zn SOD (SOD2) - mitochondrial

Question 50

In what organs is the Malate-Aspartate Shuttle active?

Answer 50

Heart, liver, and kidneys

Question 51

What is the function of the malate-aspartate shuttle?

Answer 51

Generates NADH into the mitochondrial matrix and pumps NADH through the electron transport chain at Complex 1

Question 52

What organs is the glycerophosphate-shuttle active?

Answer 52

Skeletal muscle and the brain

Question 53

What is the function of the glycerophosphate-shuttle?

Answer 53

Generate FADH2 in the inner mitochondrial membrane and join into the ETC at CoQ