Biochemistry - Pyruvate Dehydrogenase & the TCA Cycle Flashcards

1
Q

Where does conversion of pyruvate to acetyl-CoA happen?

A

Mitosol

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2
Q

Is the PDC reaction reversible or irreversible? Entirely?

A

Irreversible, but last 4 steps are reversible (first irreversible step makes the whole thing irreversible though)

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3
Q

What are the 3 enzymes of the PDC?

A

E1: pyruvate dehydrogenaseE2: dihydrolipoyl transcacetylase E3: dihydrolipoyl dehydrogenase

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4
Q

What is the cofactor in E1 of PDC? Vitamin precursor?

A

Thiamine pyrophosphate (TPP) = vitamin B1

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5
Q

What are the 2 cofactors in E2 of PDC? 2 names for 1st one? Vitamin precursor?

A
  1. Coenzyme A (panthothenic acid = B5)2. Lipoic acid
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6
Q

What are the 2 cofactors in E3 of PDC? Vitamin precursors?

A
  1. Flavin adenine dinucleotide (FAD) (riboflavin = B2)2. NAD (niacin = B3)
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7
Q

Of all of the cofactors used in PDC, which one is not considered a vitamin?

A

Lipoic acid

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8
Q

What are the 5 steps of pyruvate conversion to acetyl-CoA?

A
  1. E1: pyruvate decarboxylation: 2 Cs transfer to TPP (+ C=O reduced to C-OH) = hydroxyethyl TPP + CO22. E2: lipoic acid accepts 2Cs from TPP = LA acetylated form = acyl lipollysine3. E2: CoA accepts 2Cs from LA = Acetyl CoA + reduced LA4. E3: LA oxidized by FAD = oxidized LA (with disulfide bond) + FADH2 5. E3: FAHD2 oxidized by NAD+ + FAD + NADH
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9
Q

What are the 3 products of pyruvate conversion to acetyl CoA?

A
  1. Acetyl CoA2. NADH3. CO2
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10
Q

What are the 2 regulation mechanisms of the PDC?

A
  1. Product inhibition2. Covalent modification
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11
Q

Explain the product inhibition regulation of the PDC.

A

Acetyl CoA and NADH will drive the last 4 reactions of the PDC backward by competing with the binding sites on E2 and E3

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12
Q

Explain the covalent modification regulation of the PDC (inhibition and stimulation).

A

Inhibition: Build up of acetyl CoA and NADH will activate pyruvate dehydrogenase kinase, which will phosphorylate E1, inactivating itStimulation: Insulin will INDIRECTLY activate pyruvate dehydrogenase phosphatase which will dephosphorylate E1, activating it

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13
Q

What about CoA makes Acetyl CoA high in energy?

A

Very reactive thiol group (SH) in the beta-mercaptoethylamine end of CoA which binds the 2 carbons and contains a lot of energy

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14
Q

Can new TCA intermediates be made from acetyl-CoA?

A

NOPE

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15
Q

What are 4 ways to make TCA intermediates?

A
  1. Phosphoenolpyruvate conversion to oxaloacetate by PEPCK2. Pyruvate conversion to oxaloacetate by pyruvate carboxylase using ATP3. Pyruvate conversion to malate by malic enzyme2. Glutamate and aspartate conversion to alpha-ketoglutarate and oxaloacetate
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16
Q

What 5 steps of the TCA produces fuel (FADH2, NADH, ATP)?

A

3, 4, 5, 6, and 8

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17
Q

TCA step 1 enzyme?

A

Citrate synthase

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18
Q

TCA step 1 reactants/products?

A

Oxaloacetate + acetyl CoA + H2O = citrate + CoA-SH

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19
Q

How many Cs in citrate?

A

6

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20
Q

TCA step 1 ΔG°’? Why is this important?

A

Large negative ΔG°’ Important because oxaloacetate is present in very low concentrations in mitosol so it drives the reaction forward

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21
Q

TCA step 1: reversible or irreversible?

A

Irreversible

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22
Q

TCA step 2 enzyme?

A

Aconitase

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23
Q

TCA step 2 reactants/products?

A

Citrate –> cis-Aconitate + H2O–> Isocitrate

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24
Q

TCA step 2 ΔG°’?

A

Positive

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25
TCA step 2: reversible or irreversible?
Reversible
26
TCA step 1: cofactor?
Water
27
TCA step 2: cofactor?
Water
28
TCA step 3 enzyme?
Isocitrate dehydrogenase
29
TCA step 3 reactants/products?
Isocitrate + NAD+ --> NADH + H+ + alpha-Ketoglutarate + CO2
30
TCA step 3 ΔG°'?
Large negative
31
TCA step 3: reversible or irreversible?
Irreversible
32
TCA step 3: cofactor?
NAD+
33
How many Cs in isocitrate?
6
34
How many Cs in alpha-ketoglutarate?
5
35
TCA step 4 enzyme?
Alpha-Ketoglutarate dehydrogenase complex
36
TCA step 4 reactants/products?
alpha-Ketoglutarate + NAD+ + CoA --> Succinyl CoA + CO2 + NADH
37
TCA step 4 ΔG°'?
Large negative
38
TCA step 4: reversible or irreversible?
Irreversible
39
TCA step 4: cofactor?
NAD+ and CoA-SH
40
How many Cs in succinyl-CoA?
4
41
What is notable about the alpha-Ketoglutarate dehydrogenase complex
Similar to PDC
42
TCA step 5 enzyme?
Succinyl-CoA synthetase
43
TCA step 5 reactants/products?
Succinyl CoA + Pi + GDP --> Succinate + CoA + GTP
44
TCA step 5 ΔG°'?
Small negative
45
TCA step 5: reversible or irreversible?
Reversible
46
TCA step 5: cofactor?
GDP
47
How many Cs in succinate?
4
48
What 3 steps of the TCA are irreversible?
1, 3, and 4
49
TCA step 6 enzyme?
Succinate dehydrogenase
50
TCA step 6 reactants/products?
Succinate + FAD --> Fumarate + FADH2
51
TCA step 6 ΔG°'?
0
52
TCA step 6: reversible or irreversible?
Reversible
53
TCA step 6: cofactor?
FAD
54
How many Cs in fumarate?
4
55
TCA step 7 enzyme?
Fumarase
56
TCA step 7 reactants/products?
Fumarate + H2O --> L-malate
57
TCA step 7 ΔG°'?
Small negative
58
TCA step 7: reversible or irreversible?
Reversible
59
TCA step 7: cofactor?
Water
60
How many Cs in malate?
4
61
TCA step 8 enzyme?
Malate dehydrogenase
62
TCA step 8 reactants/products?
Malate + NAD+ --> oxaloacetate + NADH + H+
63
TCA step 8 ΔG°'?
Large positive
64
TCA step 8: reversible or irreversible?
Reversible
65
TCA step 8: cofactor?
NAD+
66
How many Cs in oxaloacetate?
4
67
Where is the enzyme of the step 4 of the TCA (succinate dehydrogenase) located?
Inner membrane of mito: complex II
68
How is the step 8 of the TCA driven forward?
Low concentrations of oxaloacetate
69
Describe Wernick's encephalopathy: 3 symptoms, 1 association, 1 cause?
- Ocular abnormalities, ataxia, global confusion- Associated with chronic alcohol abuse- Cause: Thiamine/vitamin B1 deficiency
70
Describe Pyruvate Dehydrogenase Complex Deficiency: type? onset? Symptoms type? 4 of them? Blood test? Cause?
- X-linked genetic disorder - Manifested in infancy or later childhood - Neural symptoms: intermittent ataxia, poor muscle tone, abnormal eye movements, or seizure - Elevated blood lactate with a normal pyruvate/lactate ratio- Cause: defect in pyruvate dehydrogenase
71
Describe Berberi. 5 symptoms and 1 cause?
Early manifestations include fatigue, irritability, sleep disturbance, abdominal pain, and anorexia.Cause: Thiamine=vitamin B1 deficiency
72
What is the net rxn of the TCA?
AcetylCoA + 3NAD+ + FAD + GDP + Pi + 3H2O → 2CO2 + CoA + 3NADH + FADH2 + GTP + 2H+
73
What 3 steps of the TCA require water as a cofactor?
1, 2, and 7
74
What 2 steps of the TCA produce CO2?
3 and 4
75
What kind of molecule is pyruvate?
Alpha-keto acid
76
What happens to them when alpha keto acids are formed?
Taken up by mito
77
What kind of molecule is acetyl-CoA? What is particular about these?
ThioesterVery unstable: high amount of energy
78
Delta G of pyruvate conversion to acetyl-CoA?
Large (-)
79
How is lipoic acid attached to E2?
Lys residue
80
What does the rate of oxidation of acetyl-CoA depend on?
Concentration of oxaloacetate
81
What's aspartate's role in biochemical reactions?
It can donate it's nitrogen to become fumarate or oxaloacetate
82
What happens to the acetyl-CoA when FA beta oxidation is high but gluconeogenesis using oxaloacetate is also high?
Too much acetyl CoA, can't enter TCA => ketogenesis
83
What do Wernicke encephalopathy, beriberi and pyruvate dehydrogenase complex deficiency have in common? Treatment for all three?
All have a deficient pyruvate dehydrogenase enzyme which causes neurological issues because the neurological cells do not have enough ATP. Treatment: ketogenic diet that tends to produce many ketone bodies for the brain
84
What TCA intermediate is the most oxidized?
Oxaloacetate
85
What are the 3 parts of CoA?
1. ADP2. Pantothenic acid (VB5)3. Beta-mercaptoethylamine (with SH group)
86
What does it mean for all of the cofactors used by the PDC to be essential nutrients?
We cannot synthesize them and obtain them from our diet