TCA (Krebs Cycle) Flashcards

1
Q

TCA cycle names

A

krebs, TCA, citric acid

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2
Q

final pathway of TCA

A

catabolism of carbs, AA, and FA converge and their carbon skeletons being converted to CO2

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3
Q

catabolic pathway of TCA

A

breakdown of some AA provides certain TCA cycle intermediates

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4
Q

anabolic pathways of TCA

A

-some TCA intermediates feed into biosynthetic pathways, such as the synthesis of certain amino acids

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5
Q

what provides the most energy?

A

terminal oxidation of all biomolecules

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6
Q

what carries the energy from the terminal oxidation of all biomolecules for the production of ATP in the ETC

A

NADH and FADH2

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7
Q

oxidative phosphorylation in TCA

A

ETC couple the oxidation of the reduced carriers produced by the TCA cylce with the production of ATP

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8
Q

Where is the TCA cycle located?

A

mitochondrial matric, in close proximity to the ETC

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9
Q

linear metabolic pathway

A

starts with 1 metabolite and ends up with a different one (glycolysis)

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10
Q

cycle metabolic pathway

A

starts with a certain metabolite that undergoes multiple steps forming different intermediates but in the end the same initial metabolite is regenerated. There is no net loss or gain of intermediates

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11
Q

reactions required prior the TCA cycle

A

oxidative decarboxylation of pyruvate

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12
Q

oxidative decarboxylation of pyruvate

A
  1. transported into the mitochondria
  2. converted into acetyl CoA by pyruvate dehydrogenase complex (PDH)
  3. during the reactions 1 C atom is released as CO2 and NADH is produced
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13
Q

Pyruvate dehydrogenase complex (PDH)

A
  • protein aggregate of 3 separate enzymes

- 5 different coenzymes

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14
Q

What are the 3 different enzymes that make up PDH?

A

E1, E2, E3

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15
Q

what are the 5 coenzymes associated with PDH

A
  • thiamine triphosphate, TPP
  • lipoamide
  • CoA
  • FAD
  • NAD+
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16
Q

thiamine pyrophosphate

A
  • PDH coenzyme

- from thiamine, vit B1

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17
Q

lipoamide

A
  • PDH coenzyme

- synthesized in human cells

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18
Q

CoA

A
  • PDH coenzyme

- pantothenic acid, Vit B5

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19
Q

FAD

A
  • PDH coenzyme

- from riboflavin, vit B2

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20
Q

NAD+

A
  • PDH coenzyme

- from nicotinamide, vit B3/niacin

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21
Q

regulation of PDH

A
  • phosphorlyation deactivates

- dephosphorylation activates

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22
Q

PDH kinase and phophatase can be allosterically activated or inhibited by…

A
  • substrate activation

- product inhibition

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23
Q

Active PDH

A
  • pyruvate
  • NAD+
  • ADP
  • Ca2+
  • CoA
24
Q

deactive PDH

A
  • Acetyl CoA
  • NADH
  • ATP
25
Q
  1. synthesis of citrate from acetyl CoA and oxaloacetate
A
  • condensation
  • form citrate
  • enzyme: citrate synthase
  • IRREVERSIBLE
26
Q

enzyme ofsynthesis of citrate from acetyl CoA and oxaloacetate

A

citrate synthase

27
Q

citrate synthase

A
  • enzyme for the synthesis of citrate from acetyl CoA and oxaloacetate
  • regulated simply by substrate activation or product inhibition
28
Q

citrate

A
  • precursor for FA synthesis

- inhibitor for PFK1 (feedback inhibitor)

29
Q
  1. isomerization of citrate
A

-enzyme: Aconitase

30
Q

Aconitase

A
  • enzyme for isomerization of citrate
  • Fe-S protein
  • potentially inhibited by fluoroacetate which results in citrate accumulation (suicide inhibition)
31
Q
  1. oxidative decarboxylation of isocitrate
A
  • irreversible
  • rate limiting
  • yields 1st NADH
  • releases 1 CO2
  • enzyme: isocitrate dehydrogenase
32
Q

isocitrate dehydrogenase

A
  • enzyme for oxidative decarboxylation of isocitrate
  • regulated allosterically
  • inhibitors: ATP and NADH
  • activators: ADP and Ca2+
33
Q

a-ketoglutarate

A

alos produces from the metabolism of glutamate

34
Q
  1. oxidative decarboxylation of alpha-ketogluatarate
A
  • irreversible
  • yields second NADH
  • releases 1 CO2
  • enzyme:a-ketoglutarate dehydrogenase complex
35
Q

a-ketoglutarate dehydrogenase complex

A
  • multiple copies of 3 enzymes
  • coenzymes: TPP, lipoic acid, FAD, NAD+, CoA
  • inhibitors: its products
  • activators: Ca2+
36
Q

Succinyl CoA

A

also produced from propionyl CoA derived from FA metabolism,

37
Q

vitamin deficiencies

A
  • a-ketoglutarate dehydrogenase and PDH both require multiple coenzymes derived from vitamins
  • deficiency of niacin or thiamine can cause serious central nervous system problems
38
Q

arsenic poisoning

A
  • a-ketoglutarate dehydrogenase complex and PDH both require lipoic acid
  • forms stable thiol with the -SH in lipoic acid making it unavailable
  • affects the brain causing neurological disturbances and death
39
Q
  1. cleavage of succinyl CoA
A
  • cleaves high-energy thirster bonds (used to make ATP)
  • GDP-GTP via substrate level phosphorylation
  • GTP readily converted to ATP
  • releases CoA
  • enzyme: succinate thiokinase
40
Q
  1. oxidation of succinate to fumarate
A
  • 2 H-atoms are transferred to FAD to produce FADH2

- enzyme: succinate dehydrogenase

41
Q

what enzyme is embedded in the inner mitochondrial membrane (complex II of ETC)?

A

succinate dehydrogenase

42
Q
  1. hydration of fumarate
A
  • produces malate

- enzyme: fumarase

43
Q

malate also produced in

A
  • urea cycle
  • purine synthesis
  • Phe and Tyr catabolism
44
Q
  1. oxidation of malate
A
    • free energy change
  • driven toward OAA by the next highly exergonic rxn
  • produces final NADH
  • enzyme: malate dehydrogenase
45
Q

what step produces the final NADH?

A

oxidation of malate

46
Q

oxaloacetate produced also by

A

transamination of aspartic acid

47
Q

what are the 3 irreversible steps?

A
  • synthesis of citrate
  • oxidative decarboxylatiion of isocitrate
  • oxidative decarboxylation of a-ketoglutarate
48
Q

What is the rate limiting step of TCA cycle?

A

oxidative decarboxylation of isocitrate

49
Q

what are the enzymes of the irreversible steps of the TCA?

A
  • citrate synthase
  • isocitrate dehydrogenase
  • a-ketoglutarate dehydrogenase complex
50
Q

What intermediates get consumed or produced in TCA?

A

none

51
Q

how many NADH produced in TCA?

A

3

52
Q

how many FADH2 produced in TCA?

A

1

53
Q

how many GTP produced in TCA?

A

1, by substrate level phosphorylation

54
Q

total ATP molecules/glucose molecules in glycolysis and TCA

A

38 (TCA runs twice)

55
Q

what step has substrate level phosphorylation in TCA?

A

cleavage of succinyl CoA

enzyme: succinate thiokinase

56
Q

what step produces the first NADH in TCA?

A

oxidative decarboxylation of isocitrate, the rate limiting step

57
Q

What step yields the second NADH in TCA?

A

oxidative decarboxylation og a-ketoglutarate