TCA cycle Flashcards

1
Q

Where does TCA cycle occur ?

A

Mitochondria

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2
Q

Provides 90% of the energy used by aerobic cells ?

A

TCA cycle

Final common pathway for oxidation of carbs, fatty acids and AA.

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3
Q

Pyruvate is transported in the mitochondria via ?

A

Proton symporter

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4
Q

What multienzyme complex present in the the mitochondria catalyzes pyruvate –> Acetyl-CoA ?

A

Pyruvate dehydrogenase complex (PDH)

E1, E2 & E3

3 complement enzymes present.

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5
Q

PDH complex requires what 5 coenzymes ?

A

Thiamine pyrophosphate (vit B1)
Lipoic acid
CoA (B5)
FAD (B2)
NAD (B3)

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6
Q

Activators of Pyruvate dehydrogenase complex?

A

Insulin, High AMP/ATP, high NAD/NADH

PDH is active in the DEphosophorylated state.

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7
Q

Inhibitors of Pyruvate dehydrogenase complex ?

A

High ratios of : Acetyl CoA/CoA, ATP/ADP or NADH/NAD

Activates the Kinases which inactivates PDH complex

Acetyl-CoA î when fasting (FA breakdown to spare CHO) you are already getting Acetyl-CoA from fat (other source). Glucose not converted to pyruvate therefore and can be spared for tissues who exclusively use glucose to function (brain).

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8
Q

Any enzyme under the influence of insulin will be active in the :

A

DE phosphorylated state.

Insulin removes the P (involves a phosphatase)

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9
Q

Any enzyme under the influence of glucagon will be active in what state ?

A

Phosphorylated state

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10
Q

Impact of Ca2+ on PDH complex ?

A

î activity

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11
Q

How do NADH (reducing equivalents) produced by glycolysis enter the mitochondria ?

A

Malate shuttle

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12
Q

What modification does Pyruvate goes through resulting in production of Acetyl-CoA?

A

Oxidative decarboxylation

with 5 cofactors present

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13
Q

PDH complex deficiency results in :

A

Lactic Acidosis

This enzyme deficiency results in an inability to convert pyruvate to Acetyl-CoA, causing pyruvate to be shunted to lactate via lactate dehydrogenase.
No specific treatment, dietary restriction of CHO and supplementation with thiamine may reduce sx.

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14
Q

Rare progressive neurodegenerative disease caused by defect in mitochondrial ATP production primarly as a result of mutation in genes that code for proteins of PDH complex, the electron transport chain or ATP synthase?

A

Leigh syndrome.

Both nuclear and mitochondrial DNA can be affected.

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15
Q

2 carbon entering the cycle as Acetyl-CoA are balanced by :

A

2 CO2 exiting the cycle

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16
Q

Which reaction uses FAD (riboflavin) as cofactor in the TCA cycle ?

A

Succiniate dehydrogenase

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17
Q

Acetyl-CoA to Citrate is catalyzed by what enzyme ?

A

Citrate synthase

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18
Q

Citrate synthase that catalyzes the first rx is inhibited by ?

A

Citrate (its own product)

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19
Q

3 fates of Citrate

A
  1. Enter TCA cycle (primary fate)
  2. Converted back to Acetyl-CoA in the cytosol and used as a substrate for FA synthesis.
  3. Inhibition of PFK-1 (puts glycolysis on pause)
20
Q

Citrate can regulate what enzyme of glycolysis ?

A

PFK-1

21
Q

Aconitase catalyzes what reaction?

A

Citrate to isocitrate

Isocitrate is a iron-sulfur protein (Fe-S)

22
Q

Yields the first NADH & CO2 molecules produced by the TCA cycle?

A

Isocitrate dehydrogenase

23
Q

2 regulatory enzymes of the TCA cycle

Rate limiting

A

Isocitrate dehydrogenease
a-ketaglutarate dehydrogenase

24
Q

2 enzymes of TCA cycle involved in CO2 production ?

A

Isocitrate dehydrogenase
a-ketoglutarate dehydrogenase

25
Q

Allosteric inhibitors of isocitrate dehydrogenase

A

ATP
NADH

26
Q

Allosteric activators of isocitrate dehydrogenase

A

ADP
Ca2+

27
Q

What do both PDH complex and a-ketoglutarate dehydrogenase complex have in common?

A

5 coenzymes

28
Q

Enzyme involved in substrate level phosphorylation of the TCA cycle and utilizes GDP to convert it to GTP.

The only step in the TCA cycle that directly yields a compound with high phosphoryl-transfer potential.

A

Succinyl CoA synthetase (succinate thiokinase)

Succinyl CoA to succinate + GTP

29
Q

Succinate dehydrogenase converts :

A

Succinate to fumarate

30
Q

Only enzyme of the TCA present in the inner mitochondrial membrane ?

A

Succinate dehydrogenase (functions as complex 2)

Uses FAD as a coenzyme

Other enzymes of the TCA cycle are located in the matrix.
Uses FAD rather than NAD because the reducing power of succinate is not sufficient to reduce NAD.

31
Q

What catalyzes the reaction of malate being oxidized to oxaloactetate ?

A

Malate dehydrogenase

Yields a NADH

32
Q

Which enzyme participates both in the electron transport chain and the TCA cycle ?

A

Succinate dehydrogenase (complex 2 of the electron transport chain).

33
Q

3 steps where NADH is formed in the TCA cycle :

A

Isocitrate dehydrogenase
a-ketoglutarate dehydrogenase
Malate dehydrogenase

34
Q

How many ATP produced for each Acetyl-CoA entering the TCA cycle?

A

10 /12 ATP

35
Q

Can we make glucose from Acetyl CoA?

A

Glucose to fat YES (via citrate)
Fat to glucose NO (because of oxidative decarboxylation)

Because Acetyl CoA 2Cs are released as 2CO2 during oxidative decarboxylation (2 enzymes that release CO2).

36
Q

ATP produced for aerobic glycolysis, anaerobic glycolyis & TCA cycle :

A

38
2
10/12

37
Q

Because the TCA cycle functions in both oxidative and synthetic processes, it is :

A

Amphibolic

38
Q

Thiamine pyrophosphate is the prosthetic group of 3 important enzymes :

A

Pyruvate dehydrogenase
a-ketoglutarate dehydrogenase
Transketolase

39
Q

In what condition are the plasma levels of pyruvate and a-ketoglutarate higher than normal, especially after the ingestion of glucose?

A

Beriberi

Thiamine deficiency

Low transketolase activity of red blood cells in beriberi is an easily measurable and reliable dx indicator for the disease.

40
Q

Enzymes that require lipoic acid and thus can be inhibited by Arsenic

A

Glyceraldehyde-3-phosphate dehydrogenase (Glycolysis)
PDH complex
a-ketoglutarate dehydrogenase
branched chain a-keto acid dehydrogenase

41
Q

Forms a complex with thiol (-SH) groups of lipoic acid, making that compound unavailable to serve as a coenzyme causing pyruvate and subsequently lactate to accumulate :

A

Arsenic poisoining

a-ketoglutarate level

Neurologic disturbances and death as a consequence.

42
Q

Fluoroacetate competitive inhibitor of :

A

Aconitase

43
Q

Arsenite competitive inhibitor of:

A

a-ketoglutarate

44
Q

Malonate competitive inhibitor for :

A

Succinate dehydrogenase

45
Q

In what condition are the plasma levels of pyruvate and a-ketoglutarate higher than normal, especially after the ingestion of glucose?

A

Beriberi

Thiamine deficiency

Low transketolase activity of red blood cells is an easily measurable and reliable dx indicator for the disease.