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Flashcards in TCA (Krebs Cycle) Deck (57):
1

TCA cycle names

krebs, TCA, citric acid

2

final pathway of TCA

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

3

catabolic pathway of TCA

breakdown of some AA provides certain TCA cycle intermediates

4

anabolic pathways of TCA

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

5

what provides the most energy?

terminal oxidation of all biomolecules

6

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

NADH and FADH2

7

oxidative phosphorylation in TCA

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

8

Where is the TCA cycle located?

mitochondrial matric, in close proximity to the ETC

9

linear metabolic pathway

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

10

cycle metabolic pathway

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

11

reactions required prior the TCA cycle

oxidative decarboxylation of pyruvate

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oxidative decarboxylation of pyruvate

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

13

Pyruvate dehydrogenase complex (PDH)

-protein aggregate of 3 separate enzymes
-5 different coenzymes

14

What are the 3 different enzymes that make up PDH?

E1, E2, E3

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what are the 5 coenzymes associated with PDH

-thiamine triphosphate, TPP
-lipoamide
-CoA
-FAD
-NAD+

16

thiamine pyrophosphate

-PDH coenzyme
-from thiamine, vit B1

17

lipoamide

-PDH coenzyme
-synthesized in human cells

18

CoA

-PDH coenzyme
-pantothenic acid, Vit B5

19

FAD

-PDH coenzyme
-from riboflavin, vit B2

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NAD+

-PDH coenzyme
-from nicotinamide, vit B3/niacin

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regulation of PDH

-phosphorlyation deactivates
-dephosphorylation activates

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

-substrate activation
-product inhibition

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Active PDH

-pyruvate
-NAD+
-ADP
-Ca2+
-CoA

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deactive PDH

-Acetyl CoA
-NADH
-ATP

25

1. synthesis of citrate from acetyl CoA and oxaloacetate

-condensation
-form citrate
-enzyme: citrate synthase
-IRREVERSIBLE

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enzyme ofsynthesis of citrate from acetyl CoA and oxaloacetate

citrate synthase

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citrate synthase

-enzyme for the synthesis of citrate from acetyl CoA and oxaloacetate
-regulated simply by substrate activation or product inhibition

28

citrate

-precursor for FA synthesis
-inhibitor for PFK1 (feedback inhibitor)

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2. isomerization of citrate

-enzyme: Aconitase

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Aconitase

-enzyme for isomerization of citrate
-Fe-S protein
-potentially inhibited by fluoroacetate which results in citrate accumulation (suicide inhibition)

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3. oxidative decarboxylation of isocitrate

-irreversible
-rate limiting
-yields 1st NADH
-releases 1 CO2
-enzyme: isocitrate dehydrogenase

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isocitrate dehydrogenase

-enzyme for oxidative decarboxylation of isocitrate
-regulated allosterically
-inhibitors: ATP and NADH
-activators: ADP and Ca2+

33

a-ketoglutarate

alos produces from the metabolism of glutamate

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4. oxidative decarboxylation of alpha-ketogluatarate

-irreversible
-yields second NADH
-releases 1 CO2
-enzyme:a-ketoglutarate dehydrogenase complex

35

a-ketoglutarate dehydrogenase complex

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

36

Succinyl CoA

also produced from propionyl CoA derived from FA metabolism,

37

vitamin deficiencies

-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

arsenic poisoning

-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

5. cleavage of succinyl CoA

-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

6. oxidation of succinate to fumarate

-2 H-atoms are transferred to FAD to produce FADH2
-enzyme: succinate dehydrogenase

41

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

succinate dehydrogenase

42

7. hydration of fumarate

-produces malate
-enzyme: fumarase

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malate also produced in

-urea cycle
-purine synthesis
-Phe and Tyr catabolism

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8. oxidation of malate

-+ free energy change
-driven toward OAA by the next highly exergonic rxn
-produces final NADH
-enzyme: malate dehydrogenase

45

what step produces the final NADH?

oxidation of malate

46

oxaloacetate produced also by

transamination of aspartic acid

47

what are the 3 irreversible steps?

-synthesis of citrate
-oxidative decarboxylatiion of isocitrate
-oxidative decarboxylation of a-ketoglutarate

48

What is the rate limiting step of TCA cycle?

oxidative decarboxylation of isocitrate

49

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

-citrate synthase
-isocitrate dehydrogenase
-a-ketoglutarate dehydrogenase complex

50

What intermediates get consumed or produced in TCA?

none

51

how many NADH produced in TCA?

3

52

how many FADH2 produced in TCA?

1

53

how many GTP produced in TCA?

1, by substrate level phosphorylation

54

total ATP molecules/glucose molecules in glycolysis and TCA

38 (TCA runs twice)

55

what step has substrate level phosphorylation in TCA?

cleavage of succinyl CoA
enzyme: succinate thiokinase

56

what step produces the first NADH in TCA?

oxidative decarboxylation of isocitrate, the rate limiting step

57

What step yields the second NADH in TCA?

oxidative decarboxylation og a-ketoglutarate