Lecture 10: Mitochondrial Bioenergetics Flashcards Preview

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Flashcards in Lecture 10: Mitochondrial Bioenergetics Deck (65):
1

________ is the activated form of acetate

Acetyl CoA

2

Where is he high energy bond in acetyl CoA located?

S-CoA

3

What is the deltaG of acetyl coA?

-7.5 kcal/mol

4

How does pyruvate enter the mitochondria?

Mitochondrial pyruvate carrier (MPC)

5

________ catalyzes the deccarboxylation of pyruvate once pyruvate enters the mitochondria

Pyruvate dehydrogenase complex (PDC)

6

In a phosphatase deficiency, PDC is always in the inactive form. Is this phosphorylated or dephosphorylated?

Phosphorylated

7

What are the symptoms of a phosphatase (affecting PDC) deficiency?

Glucose is converted to lactate rather than acetyl CoA, resulting in constant lactic actidosis

- The CNS is the most effected

8

In patients with a PDC deficiency, it is important to limit ____ in their diet to prevent further buildup of lactic acid

Alanine because Ala is converted to pyruvate via a transamination reaction hen pyruvate cant be processed so its converted to lactate causing further buildup

9

In a high energy charge, what inhibits PDH?

NADH
Acetyl CoA
ATP

10

In a low energy charge, what stimulates PDH?

Pyruvate
ADP

11

What 3 steps of TCA are regulated?

OAA -> Citrate (citrate synthase)
Isocitrate -> Alpha-ketoglutarate (Isocitrate dehydrogenase)
Alpha-ketoglutarate -> Succinyl CoA (alpha-ketoglutarate dehydrogenase)

12

What is the rate limiting step of TCA?

Isocitrate -> alpha-ketoglutarate (isocitrate dehydrogenase)

13

Where in TCA is there substrate level phosphorylation for a high energy bond?

Succinyl CoA -> Succinate (Succinate thiokinase)

- Creates GTP

14

How many moles of ATP is generated from 1 mole of glucose oxidized via TCA cycle?

20 -> 10moles of ATP/1 pyruvate X 2 pyruvate/1 mole of glucose = 20

15

What are the two major anaplerotic reactions that provide intermediates to replenish the TCA cycle?

1) Degradation of amino acids
2) Carboxylation of pyruvate (pyruvate -> OAA -> gluconeogenesis)

16

What amino acids can be converted into OAA?

Asn -> Asp -> OAA

17

What amino acids can be converted into fumarate?

Phe, Tyr, Asp

18

What amino acids can be converted into succinyl CoA?

Thr, Met, Ile, Val -> Propionyl CoA -> Succinyl CoA

19

What amino acids can be converted into alpha ketoglutarate?

Gln, Pro, His, Arg -> Glutamate -> Alpha-ketoglutarate

20

Alpha ketoglutarate can form what amino acids?

Alpha ketoglutarate -> Glutamate -> Gln, Pro, Arg

21

What is 2-Oxoglutaric aciduria?

A rare disorder with global developmental delay and sever3e neurological problems in infants
- Metabolic acidosis, severe microcephaly, mental retardation

22

What is Fumarase deficiency?

Characterized by severe neurological impairment. Fatal outcome within first 2 years of life.
- Encephalomyopathy, dystonia, increased urinary excretion of fumarate, succunate, alpha-ketoglutarate, and citrate (can find all in urinalysis
**Autosomal recessive**

23

What is succinyl CoA synthetase (SCS) deficiency?

Associated with mutations two out of three subunits making up the enzyme -> SUCLA2 and SUCLG1
- These genes encode the beta subunit of the ADP-forming SCS and alpha-ketoglutarate subunit of SCS

24

What symptoms is mitochondrial depletion syndrome associated with?

Profound hypotonia, progressive dystonia, muscular atrophy, and severe sensory neural hearing impairment

25

Where does oxidative phosphorylation occur?

Inner mitochondrial membrane

26

Where does TCA and FA oxidation occur?

Mitochondrial matrix

27

What is an electron only transfer?

Electrons are transferred between two metal ions

**The oxidant is always on the side of the reaction with the electrons**

28

What is a reducing-equivalent transfer?

Involves transfer of a proton and an electron

29

__________________ is a measure of the affinity of a redox pair of electrons and uses volt (V) as the unit

Standard redox potential

30

Does a redox pair with a lower standard redox potential have a higher or lower affinity for electrons?

Lower -> hence gives them u easily to a redox pair with a higher standard redox potential

31

What is the relationship between Gibbs free energy and standard redox potential?

They are inversely related

32

Electrons flow from the molecules with ______ standard redox potential to that with _______ standard redox potential

Lower; highest

33

O2 from ETC complex 1 and 3 becomes a superoxide anion. What enzyme is used to convert a superoxide anion to hydrogen peroxide and what is its cofactor?

SOD; cofactor = Mn or Mg

34

Once a superoxide anion is converted to hydrogen peroxide, it can be made into either water or GSSG. What enzyme is used to convert it to water?

Catalase

35

Once a superoxide anion is converted to hydrogen peroxide, it can be made into either water or GSSG. What enzyme is used to convert it to GSSG?

GSH peroxydase

GSSG reductase or thioreoxin reductase can then convert that to GSH which is a hydroxyl radical

36

When there is an overproduction of RNS and ROS, what 3 things are damages induced on?

DNA
Proteins
Lipids

37

What are the 3 key goals of OxPhos?

1) To transfer electrons from NADH and FADH2 to O2
2) To establish a proton gradient across the inner mito membrane
3) To synthesize ATP

38

Electron transfer through the respiratory chain lead to the pumping of H+ from __________ to ________

Matrix -> inner mito space

39

What are the 2 factors that constitute a proton motive force (pmf) to drive ATP synthase?

1) pH gradient
2) Membrane potential

40

What is the necessary power needed by ATP synthase to form ATP?

7.3kcal/mol

41

What are the inhibitors of ATP synthase (complex 5)

Oligomycin

42

What is the role of oligomycin

Inhibits ATP synthase by disrupting proton transport through the channel

43

CoQ (ubiquinone) is a lipophilic molecule that is not a prosthetic group for which complex?

III

44

What cofactors are in complex I of ETC?

FMN and Fe-S

45

What cofactors are in complex II of ETC?

Fe-S

46

What cofactors are in complex III of ETC?

Cyt-b
Cyt-C1
Fe-S

47

What cofactors are in complex IV of ETC?

Cu
Cyt-a
Cyt-a3

48

What inhibits complex I of ETC?

Amytal
Rotenone
Myxothiazol
Piericidin A

49

What inhibits complex 2 of ETC?

Malonate

50

What inhibits complex III of ETC?

Antimycin

51

What inhibits complex IV of ETC?

CO
Cyanide
H2S

52

How do uncoupling proteins work?

P-ADP uncoupled from the electron transfer, protons reenter he mito matrix from the intermembrane space, TCA cycle and electron transfer to O2 are accelerated, ATP synthase is inhibited and HEAT is generated

53

Explain the malate-aspartate shuttle

Used to shuttle NADH into the mitochondria
OAA + NADH -> Malate -> Malate into mito matrix -> release of NADH in matrix -> OAA formed -> alpha-ketoglutarate and aspartate -> alpha-ketoglutarate leaves mito and goes to cytosol where the cycle is repeated

54

Explain the glycerophosphate shuttle

Used to get NADH into the mitochondria

DHAP -> Glycerol-3-P -> Intermembrane space of mito -> DHAP with transfer of FADH2 and DHAP goes back to cytosol to repeat the process

55

Where does the malate-aspartate shuttle operate?

Heart, liver, kidney

56

Wha does the malate-aspartate shuttle generate?

NADH in mito matrix

57

Where does the glycerophosphate shuttle operate?

In skeletal muscle and the brain

58

What does the glycerophosphate shuttle generate?

FADHs in the inner mito membrane

- Joins ETC at CoQ

59

What was the first diagnosed mitochondrial disease?

Luft's disease

60

What are the 2 primary causes of mitochondrial diseases?

Defect in nuclear DNA (nDNA) encoding the mito proteins
Defect in mitochondrial DNA (mDNA)

61

What are some secondary causes of mitochondrial diseases?

Ischemia, reperfusion, cardiovascular diseases, renal failure, alcohol, smoking, drugs, aging

62

What are the metabolic features of mitochondrial diseases?

Low energy production
Increased free radical production
Lactic acidosis

63

What type of inhibitor does CO act as in the ETC?

Competitive (raises Km)

64

What type of inhibitor does CN and H2S act as in ETC?

Noncompetitive (decreases Vmax)

65

How does an aspirin overdose effect ETC?

At high concentrations, salicylate uncoupled oxidative phosphorylation by disrupting the proton gradient across the inner mitochondrial membrane and causes the dissipation of energy as heat