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MCM - Rusheil > Mitochondrial Bioenergetics > Flashcards

Mitochondrial Bioenergetics Flashcards

1
Q

Acetyl-CoA obtained from:

A

Carbohydrates: Decarboxylation of Pyruvate
Glucose (6C) —> 2 Pyruvate (3C) —> 2 Acetyl-CoA (2C)

Lipids: beta-oxidation of FA
TAG —> FA —> Acetyl-CoA

Proteins: Breakdown of various AA —> Acetyl-CoA

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2
Q

Free energy of Aceytl-CoA (delta G)

A

-7.5 kcal/mol

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3
Q

How Pyruvate enters mitochondria?

Enzyme for decarboxylation of Pyruvate to Acetyl-CoA?

A

Pyruvate Mitochondrial Carrier

Pyruvate Dehydrogenase Complex (PDC) (releases NADH and CO2)

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4
Q

Pyruvate Dehydrogenase Complex (PDC)

A

Decarboxyates pyruvate into CO2 and forms Acetyl-CoA and NADH.

PDC: 3 Enzymes + 5 Coenzymes
- Coenzymes: Thiamine Pyrophosphate TPP (Vitamin B1), lipoic acid, FAD (Vitamin B2 - Riboflavin), CoA (Vitamin B5 - Pantothenic Acid), NAD+ (Vitamin B3 - Niacin)

Inactive PDC = Pyruvate converting to lactate —> build-up —> Lactic Acidosis

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5
Q

Pyruvate Dehydrogenase Phosphatase (PDP)

A

Activates PDC by dephosphorylation

PDP activated by: Ca2+ , Mg2+ —> PDC activation

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6
Q

Pyruvate Dehydrogenase Kinase (PDK)

A

Inactivates PDC by phosphorylation

PDK activated by: Acetyl-CoA , NADH , ATP (feedback inhibition)

PDC inactivated by: Pyruvate, CoA, NAD+, ADP (feed-forward stimulation of PDC via inactivation of PDK)

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7
Q

Citrate Synthase rxn and regulation

A

Catalyzes TCA reaction:
oxaloacetate + Acetyl-CoA —> Citrate

Stimulated by: Insulin, Acetyl-CoA, Oxaloacetate

Inhibited by: Citrate, NADH, Succinyl-CoA, ATP

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8
Q

Isocitrate Dehydrogenase (reaction and regulation)

A

Catalyzes TCA reaction:
Isocitrate —> alpha-ketoglutarate

Rate-limiting Enzyme
Produces NADH and CO2

Stimulated by: ADP, Ca2+

Inhibited by: NADH, ATP

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9
Q

Alpha-ketoglutarate Dehydrogenase Complex (reaction and regulation)

A

Catalyzes TCA reaction:
Alpha-ketoglutarate —> Succinylcholine-CoA

Produces NADH and CO2

Stimulated by: Ca2+

Inhibited by: NADH, Succinylcholine-CoA, ATP, GTP

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10
Q

Anabolic molecules in TCA

A

Malate: malate—>oxaloacetate—>PEP—>glucose

Citrate: Citrate—>Acetyl-CoA —>FA synthesis

alpha-ketoglutarate: Glutamate—> Glutamine, Proline, Arginine

Oxaloacetate: Aspartate, Aspargine

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11
Q

2-Oxoglutaric Aciduria

A

Rare disorder with global developmental delay / severe neurological problems

  • metabolic acidosis
  • severe microcephaly
  • mental retardation
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12
Q

Fumarase Deficiency

A

Severe Neurological impairment, fatal outcome within 2 years of life

  • increased urinary excretion of fumarate, succinct, alpha-ketoglutarate and citrate
  • encephalomyopathy
  • dystonia

Autosomal Recessive disorder

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13
Q

Succinyl-CoA synthetase (SCS) deficiency

A

Associated with mutation 2/3 subunits making up enzyme

Mutated genes: SUCLA2, SUCLG1

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14
Q

Standard reduction potential relation with free energy change

A

ΔG’ = -nFΔE’

Standard reduction potential and Standard free energy change are inversely related

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15
Q

OxPhos complexes that create ROS

A

Respiratory chain complex I and III

They produce superoxide anions and hydrogen peroxide (some of which gets reduced by glutathione)

Overproduction of ROS: Damage to DNA, Protein, lipids
Normal production: Growth, hormone synthesis, inflammation

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16
Q

Proton motive force (PMF)

A

Constitutes (1) pH gradient. (2) Membrane potential

17
Q

ATP Synthase

A

Complex IV of the respiratory chain.

Harnesses energy contained in pmf
7.3 kcal/mol to form ATP

18
Q

Oligomycin

A

Drug that disrupts proton transport through the ATP synthase channel

19
Q

Cytochrome-c

A

Mobile electron-carrying molecule moving between complex III and IV of the respiratory chain.

Travels in the intermembrane space and the inside of the inner mitochondrial membrane (where the chain complexes are located)

20
Q

CoQ (ubiquinone)

A

A lipophilic molecule that is a mobile electron carrier for complexes I and II, bringing electrons to complex III.

21
Q

Uncoupling in proton gradient

A

Normally in OxPhos, electron transfer is coupled with the proton gradient.

When gradient is disrupted —> Uncoupling occurs

  • ATP synthesis uncoupled from electron transfer
  • Protons re-enter matrix from intermembrane space
  • ATP synthesis inhibited
  • HEAT GENERATED (thermogenesis)
22
Q

How NADH (reduced) crosses mitochondrial membrane

A

Electron transfer via

(1) malate-aspartate shuttle: heart, liver, kidneys —> NADH (e-) enters ETC at COMPLEX I
(2) Glycerophosphate shuttle: skeletal muscle, brain —>FADH2 (e-) enters ETC at CoQ (ubiquinone)

23
Q

Where malate-aspartate shuttle takes place?

A

Heart
Liver
Kidneys

24
Q

Where glycerphosphate shuttle takes place?

A

Skeletal muscle

Brain

MCM - Rusheil (6 decks)

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