Exam 1 Ch 17 Flashcards

1
Q

How many reactions and enzymes in the citric acid cycle

A

8

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2
Q

What does the citric acid cycle do

A

oxidizes acetyl-CoA

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3
Q

what does it yield

A

o 2× CO 2
o 3× NADH
o 1× FADH 2
o 1× ATP or GTP

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4
Q

Where are the enzyems located

A

Mitochondion matrix

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5
Q

What do the intermediates of the kreb TCA cycle serve as

A

precursors for other biosyntehsis pathways

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6
Q

Is acetyl-CoA a high or low energy compound

A

High

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7
Q

Whaat enzyme catalyzes the synth of acetyl-CoA

A

pyruvate dehydrogenase which is an oxidoreductase

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8
Q

How many subunits in PDH

A

Human: 5 (heterotetramer)
E. coli: 3 (homodimers)

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9
Q

List the five cofactors of pyruvate

A

Thiamine pyrophosphate
Lipoic acid
Coenzyme A (CoA)
Flavin adenine dinucleotide (FAD)
Nicotinamide adenine dinucleotide (NAD+)

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10
Q

What is a cosubstrate

A

cofactor that is temporarily and loosely bound to the enzyme

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11
Q

What is a prosthetic group?

A

Tightly bound to enzyme

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12
Q

Which of the five cofactors are cosubstrates

A

Coenzme A (CoA) and
Nicotinamide adenine dinucleotide (NAD+)

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13
Q

What are the prosthetic cofactors

A

thiamine pyrophosphate (TPP)
lipoic acid
flavin adenine dinucleotide (FAD)

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14
Q

How many of the 8 reactions in the citric acid cycle are irreversible

A

3.

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15
Q

What’s the input of the TCA cycle

A

acetyl-CoA

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16
Q

Catalyzed by pyruvate dehydrogenase (PDH)
o E. coli PDH has 3 different subunits

A
  1. Pyruvate Dehydrogenase (E1 ) 24 copies
  2. Dihydrolipoyl Transacetylase (E2 ) 24 copies
  3. Dihydrolipyl Dehydrogenase (E3 ) 12 copies
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17
Q

SYnthesis of acetal CoA Contains five catalyzed reactions

A
  1. Pyruvate decarboxylation
  2. Lipoamide acetylation
  3. CoA acetylation
  4. Thiol-Disulfide Exchange
  5. Hydride Transfer
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18
Q

What happens in reaction one of TCA cycle?

A

Acetylation of oxaloacetate by acetyl-CoA. Three sequential reactions
1. Reversible Acetyl-CoA tautomerization
2. Reversible nucleophilic addition of Acetyl-CoA to Oxaloacetate
3. Irreversible hydrolysis of Citryl-CoA to Citrate & CoA

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19
Q

What are the Three sequential reactions of reaction 1

A

Three sequential reactions
1. Reversible Acetyl-CoA tautomerization
2. Reversible nucleophilic addition of Acetyl-CoA to Oxaloacetate
3. Irreversible hydrolysis of Citryl-CoA to Citrate & CoA

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20
Q

What is the enzyme in reaction one of TCA and classification and cofactor

A

Citrate Synthase. Transferase, homodimeric. CoA cofactor (cosubsttrate)

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21
Q

What is reaction 2 of TCA

A

Isomerization of citrate to isocitrate.

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22
Q

What is the enzyme of reaction 2 and class and cofactor

A

Aconitase. Lyase. monomeric. cluster cofactor.

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23
Q

What are the reactions in the second reaction of the tca cycle

A

Dehydration of citrate to cis-aconitate, Hydration of cis-aconitate to isocitrate. Both reversible

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24
Q

What happens in reaction 3

A

Oxidative decarboxylation of isocitrate

25
What is the enzyme in reaction 3 and class and cofactor
Isocitrate dehydrogenase homodimeric oxidoreductase Mg2+ or Mn2+
26
What reaections does reaction 3 consist of
Two sequential irreversible reactions 1. Dehydrogenation of Isocitrate to Oxalosuccinate 2. Decarboxylation of Oxalosuccinate to α-Ketoglutarate`
27
What happens in reaction 4
α-Ketoglutarate Oxidative Decarboxylation
28
what is reaction 4 catalyzed by
oxoglutarate dehydrogenase. It's similar to pyruvate dehydrogenase and is a multienzyme complex. Consists of 1. Oxoglutarate Dehydrogenase (oxidoreductase) o Thiamine Pyrrophosphate (TPP) cofactor 2. Dihydrolipoyl Succinyltransferase (transferase) o Cofactors: Lipoic acid, CoA (cosubstrate) 3. Dihydrolipoyl Dehydrogenase (oxidoreductase) o Cofactors: FAD, NAD+ (cosubstrate)
29
Reaction 5
Substrate-level Phosphorylation of GDP
30
Enzymes in reaction 5
* Catalyzed by Succinyl-CoA Synthetase (SCS)  Heterodimeric  Classified as a ligase  CoA cofactor
31
Reaction 5 reactions
1. Phosphorylation of Succinyl-CoA via SN2 2. Phosphorylation of active site His 3. Phosphorylation of GDP
32
Reaction 6
Dehydrogenation of Succinate to Fumarate
33
Reaction 6 enzymes
* Catalyzed by Succinate Dehydrogenase (SDH, Complex II)  Heterotetramer  Classified as an oxidoreductase  Cross-linked FAD & [4Fe-4S] cluster cofactors
34
reaction 6 reactions
Three reversible reactions 1. Proton abstraction of Succinate 2. Hydride transfer to FAD 3. Electron transfer to Ubiquinone
35
Reaction 7
Hydration of Fumarate to Malate
36
reaction 7 enzymes
* Catalyzed by Fumurase (Fumarate Hydratase)  Homodimer (Class I), Homotetramer (Class II)  Classified as a lyase  No cofactors
37
Reaction 7 reactions
Two reversible reactions 1. Nucleophilic addition of Hydroxide to Fumarate 2. Protonation of Malate
38
Reaction 8
Dehydrogenation of Malate to Oxaloacetate
39
Reaction 8 enzymes
* Catalyzed by Malate Dehydrogenase (MDH)  Homodimeric (two isozymes)  Classified as an oxidoreductase  NAD cofactor (cosubstrate)
40
reaction 8 reactions
Two reversible reactions 1. Hydride transfer to NAD+ 2. Deprotonation by His
41
TCA Cylce Enzymes
1. Citrate Synthase 2. Aconitate Hydratase (Aconitase) 3. Isocitrate Dehydrogenase 4. Oxoglutarate Dehydrogenase 5. Succinyl-CoA Synthetase 6. Succinate Dehydrogenase (Complex II) 7. Fumarate Hydratase (Fumarase) 8. Malate Dehydrogenase
42
1. Citrate Synthase
Transferase
43
2. Aconitate Hydratase
lyase
44
3.Isocitrate Dehydrogenase
oidoreductase
45
4.Oxoglutarate Dehydrogenase
Multienyme complex
46
5. Succinyl-CoA Synthetase
ligase
47
Succinate Dehydrogenase
Oxidoreductase
48
Fumarate hydratase
lyase
49
Malate Dehydrogenase
oxidoreductase
50
enzyme class of : 1. Citrate Synthase 2. Aconitate Hydratase (Aconitase) 3. Isocitrate Dehydrogenase 4. Oxoglutarate Dehydrogenase 5. Succinyl-CoA Synthetase 6. Succinate Dehydrogenase (Complex II) 7. Fumarate Hydratase (Fumarase) 8. Malate Dehydrogenase
Enzymes of the Citric Acid Cycle 1. Citrate Synthase  transferase 2. Aconitate Hydratase (Aconitase)  lyase 3. Isocitrate Dehydrogenase  oxidoreductase 4. Oxoglutarate Dehydrogenase  multi-enzyme complex 5. Succinyl-CoA Synthetase  ligase 6. Succinate Dehydrogenase (Complex II)  oxidoreductase 7. Fumarate Hydratase (Fumarase)  lyase 8. Malate Dehydrogenase  oxidoreductase
51
List what is made at each step of the TCA cycle. What is the molecule turned into
Start with Acetyl-CoA Citrate Isocitrate alpha-ketoglutarate succinyl-CoA Succinate Fumarate Malate Oxaloacetate
52
List the enzymes in each step
Citrate synthase Aconitase Isocitrate dehydrogenase Alpha-ketoglutarate dehydrogenase complex Succinyl-CoA synthase Succinate dehydrogenase Fumarase Malate dehydrogenase
53
List the products of each step
Citrate to Isocitrate: nothing Isocitrate to alpha ketoglutarate: NADH, CO2 Alpha-ketoglutarate to succinyl-CoA: CoA into cycle, NADH and Co2 out of cycle Succinyl-CoA to Succinate: GTP, CoA Succinate to Fumarate: FADH2 Fumarate to Malate: H2O Malate to Oxaloacetate: NADH
54
Name parts of cycle that create NADH
Isocitrate to alpha-ketoglutarate Alpha-ketoglutarate to succinhyl-CoA Succinate to Fumarate Malate to Oxaloacetate
55
Name part of cycle that makes GTP
Succinyl-COA to Succinate
56
What is PDH (pyruvate dehydrogenase) regulated by?
Product inhibition and covalent modification. high levels of NADH and acetyl CoA inhibit PDH and drive the reverse reaction of E3 and E2
57
How is the flux of TCA cycle regulated
it is controlled through several enzymes via Substrate availability Product inhibition competitive feedback allosteric modulation 1. Substrate availability  Pyruvate, Acetyl-CoA 2. Product inhibition  NADH 3. Competitive feedback inhibition  Succinyl-CoA competes with Acetyl-CoA 4. Allosteric modulation  ADP, Ca 2+ activators  ATP inhibitor
58
How are TCA cylce metabolites replenished?
Anaplerotic (replenishing) reactions Gluconeogenesis- oxaloacetate Acetyl-CoA synthesis- acetyl-CoA Amino acids- oxoglutarate