TBL10 Flashcards

TCA Cycle and Ox. Phos

1
Q

pyruvate dehydrogenase complex

A

thiamin (Vitamin B1)-dependent, essential for glucose oxidation in the brain. Deficiency leads to accumulation of lactate=> lactatic acidosis

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2
Q

pyruvate oxidation

Gluconeogenic amino acids

from protein metabolism

A

Alanine, cysteine, glutamic acid, glycine, serine, threonine, tryptophan

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3
Q

pyruvate oxidation

How to make pyruvate

A

Glucogenic amino acids (protein metabolism) and glycerol (from fat metabolism) –> Pyruvate

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4
Q

Anaerobic glycolysis

state

A

during cellular hypoxia or when energy demand is rapidly increased to exceed rate at which ox phos can provide sufficient ATP
short intense exercise (10 sec-2min)

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5
Q

Lactate dehydrogenase

Anaerobic glycolysis

A

pyruvate+ NADH–> lactate +NAD+ +2ATP

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6
Q

Gluconeogenesis pathway

A

glucose is formed from non-hexose precursors such as glycerol, lactate, pyruvate, and glucogenic amino acids

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7
Q

precursors

Gluconeogenesis

A

glycerol, lactate, pyruvate, and glucogenic amnio acids n

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8
Q

Ketogenic Amino Acids

Relationship of Acetyl CoA with TCA Cycle

A

Phe, Leu, Isn, Lys,Thr, Trp, Tyr

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9
Q

How to form Acetyl CoA

Relationship of Acetyl CoA with TCA Cycle

A

Ketogenic Amino Acids + FAs

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10
Q

Acetyl CoA can:

Relationship of Acetyl CoA with TCA Cycle

A
  1. relate carbohydrate, protein, and lipid metabolism to each other
  2. enter TCA cycle
  3. be involved in synthesis of Acetylcholine, cholesterol, FAs, and ketone bodies
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11
Q

Where does Krebs Cycle take place?

A

mitochondrial matrix

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12
Q

metabolic pathway of TCA Cycle

A

consumes acetate as Acetyl CoA and 2H2O
generates: 3NADH, 1FADH2, 1GTP, net yield 12 ATP, oxaloacetate

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13
Q

NADH

A

fed into Ox. phos. during ETC
NADH and FADH2 are essential for ox. phos.

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14
Q

FADH2

A

transferred from ETC
covalently attached to succinate dehydrogenase
facilitates transfer of e- to Co-Q/ubiquinone

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15
Q

TCA Cycle Intermediates

Acetyl-CoA

A
  • can be converted to: AAs, FAs, cholesterol, ketone bodies, acetoacetate,3-beta-hydroxybutyrate, and acetone
  • synthesizes: Acetylcholine, cholesterol, FAs, ketone bodies
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16
Q

TCA cycle intermediates

Ketone Bodies

A
  • produced from FAs by liver
  • converted to Acetyl-CoA, enters citric acid cycle
  • source of energy in prolonged fasting
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17
Q

TCA cycle intermediates

alpha-ketoglutarate

A

directly used to form AAs (glutamate to GABA, Gln, Pro, Arg)

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18
Q

TCA cycle intermediates

Succinyl CoA+Glycine

A

form poryphyrin/heme part of Hgb

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19
Q

TCA cycle intermediates

Succinyl CoA

A
  • converts into succinate, lead to increased formation of GTP
  • Succinyl CoA+Glycine–> used in poryphyrin/Heme part of Hgb
20
Q

TCA cycle intermediates

OXALOACETATE

A

Phosphoenolpyruvate

21
Q

TCA cycle intermediates

Protons-How generated?

A

NADH later use in ox.phos

22
Q

Krebs cycle activators

A

Glutamine, Glutathione, Fe, NADH, Carnosine, exercise

23
Q

Krebs cycle inhibitors

A

Aconitase inhibition:Zn excess and other inhibitors
Metals: Pb, Cd, Cr, Mn, Al, Fe excess
Metformin
Vitamin B12 Deficiency

24
Q

Terminal electron acceptor of ETC

Aerobic conditions

A

O2

25
Q

electron acceptor of ETC (anaerobic conditions)

A

sulphate

26
Q

ETC Complex I

NADH Dehydrogenase

A
  • accepts electrons from TCA cycle’s electron carrier NADH
  • NADH reduces FMN to FMNH2, then oxidized to Ubiquinone Coenzyme Q
  • Reduced product: Ubiquinol QH2
27
Q

Complex I pathology

Rotenone

A

Pesticide, fish poison
inhibits NADH-Ubiquione Oxidoreductase
Symptoms: vomiting, incoordination, convulsions, CNS depression and respiratory distress, bradycardia, arrythmia

28
Q

ETC Complex II

Succinate Dehydrogenase

A
29
Q

ETC Complex III

Complex III Inhibitors: Dimercaprol

A

chelating agent used to treat acute poisioning by lead, mercury, arsenic, or gold

30
Q

ETC Complex III

Complex III Inhibitors: Naphthoquinone

A
  • analog of coenzyme Q,
  • competitive inhibition of active site of ubiquinone
  • treats pneumocystis pneumonia and malaria
31
Q

ETC Complex 3

Antimycin A

A
  • binds Q site of cytochrome c reductase
  • inhibits oxidation of ubiquinol to ubiquinone
  • no production of ATP, disrupts formation of proton gradient
  • may prematurely leak electrons to O2 resulting in formation of free radicals
32
Q

Complex IV

Cytochrome C Oxidase

A
  • contain Cu ions and heme groups
  • 4 e- removed from Cytochrome C and transferred to O2 and protons producing 2 H2O
  • 8H+ removed (4 translocated across membrane) to electrochemical gradient
33
Q

Complex iV

Cytochrome C Inhibitors

A
  • CO, HS, Azide, Cyanide
34
Q

Complex IV

Cytochrome C Inhibitors: Cyanide

A
  • attaches to iron, disrupts ETC
35
Q

Cyanide Poisoning

A

hypoxia leads to neurologic/CV compromise: headache, vertigo, confusion, pallpitations, shortness of breath, vomiting, seizures, low BP, cardiac arrest, lactic acidosis

36
Q

Chemiosmosis

Chemiosmotic coupling hypothesis

A

ETC and OxPhos are coupled by electrochemical proton gradient through ATP Synthase
1. a membrane impermeable to protons
2. electron treansport by cellular respiratory chain pumps protons out of mitochondria
3. proton flow into the mitochondria depends on presence of ADP and Pi inside mitochondria
4. reversible ATPase activity

37
Q

chemiosmosis

transport of e-

A

NADH+2H+ + 1/2O2–> H2O+ NAD

38
Q

I Glucose produces

A
  • 38 ATP: 2 from glycolysis, 2 from TCA, 34 from ETC
39
Q

Uncoupling of ETC and OxPhos

A
  • thermogenin
  • will result in increased ADP and Pi in mitochondria
  • OxPhos produces ROS
40
Q

Drugs that inhibit Ox Phos

Oligomycin A (antibiotic)

A
  • selectively inhibits ATP synthase by blocking its proton pump
  • induces apoptosis
41
Q

Drugs that inhibit Ox Phos

2,4-Dinitrophenol

A
  • antiseptic, non-selective bioaccumulating pesticide
  • inhibits ox phos
  • disrupts proton gradient, causes uncoupling
42
Q

PDHC Deficiency

A
  • X-linked, neurodegenerative
  • Leigh Syndrome
  • Fumarase Deficiency
  • mutations of IDH
43
Q

Leigh Syndrome

A
44
Q

Fumarase Deficiency

A
45
Q
A