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Biochemistry > citric acid cycle > Flashcards

citric acid cycle Flashcards

1
Q

TCA cycle - a biochemical hub of the intermediary metabolism:

  1. oxdizing carbons fuels for harvesting:
  2. it is ____ (e.g. catabolism and anabolism)
  3. source of precursors for
  4. takes place inside ____
A
  1. high energy electrons
  2. amphibolic
  3. biosynthesis
  4. mitochondria
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2
Q

other names of TCA cycle

A

Tricarboxylic acid cycle (TCA)

citric acid cycle

krebs cycle

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3
Q

precursor stage 1 of TCA

A

fats, polysaccharides, and proteins are reduced to fatty acids and glycerol, glucose and other sugars, and amino acids

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4
Q

precursor stage 2 of TCA

A

fatty acids and glycerols, glucose and other sugars, and amino acids are all converted to Acetyl CoA (common currency)

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5
Q

1 mol of NADH =

A

2.5 moles ATP

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6
Q

1 mol of FADH2 =

A

1.5 moles ATP

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7
Q

1 mol of GTP =

A

1 mol ATP

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8
Q

TCA cycle overview: oxidation of 2-carbon units to produce:

A

2 CO2 molecules

1 GTP

High energy electrons (3 NADH and 1 FADH2)

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9
Q

how is glucose converted into acetyl CoA?

A

glucose (6C) –oxidation–> 2 pryuvate (3C) –decarboxylation–> 2 Acetyl CoA (2C)

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10
Q

how are lipids converted into acetyl CoA?

A

TAG –> fatty acids –betaoxidation–> acetyl CoA (2C)

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11
Q

how are proteins converted to Acetyl CoA?

A

breakdown into various amino acids –> acetyl CoA

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12
Q

how is pyruvate converted to acetyl CoA?

A
  1. decarboxylation
  2. oxidation
  3. transfer acetyl group to CoA (by coupling with NAD+ –> NADH rxn)
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13
Q

aerobic glycolysis coupled with oxidative phosphorylation:

  1. pyruvate must enter:
  2. pyruvate utilizes:
  3. ______ catalyzes the decarboxylation of pyruvate
A
  1. the mitochondira
  2. mitochondrial pyruvate carrier (MPC)
  3. pyruvate dehydrogenase complex (PDC) or (PDH)
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14
Q

pyruvate dehydrogenase reaction:

  1. requires 3 enzymes:
  2. requires 5 coenzymes: catalytic cofactors and stoichiometric cofactors
A
  1. E1 (TPP), E2(Lipoic acid), E3(FAD)

2.

catalytic cofactors:

  • thiamine pyrophosphate (TPP/Vitamin B1)
  • lipoic acid
  • FAD

stoichiometric cofactor:

  • CoA
  • NAD+
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15
Q

phosphorylated version of PDC/PDH is

A

inactive

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16
Q

dephosphorylated version of PDC/PDH is

A

active

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17
Q

overall reaction of pyruvate –> Acetyl CoA

A

pyruvate + NAD+ + CoA → Acetyl CoA + CO2 + NADH + H+

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18
Q

high [aceytl CoA] directly inhibits

A

E2

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19
Q

accumulation of ADP and pyruvate activates phosphatases which dephosphorylates ____

A

PDH/PDC (making it active)

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20
Q

increased levels of acetyl CoA will inhibit

A

PDH/PDC

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21
Q

the TCA cycle occurs under

A

aerobic conditions and procuces more energy from glucose than glycolysis

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22
Q

the TCA cycle takes place in the

A

mitochondria

23
Q

what enzyme links glycolyis to the TCA cycle

A

pryuvate dehydrogenase (PDH/PDC)

24
Q

first step of TCA cycle

A

4-carbon oxaloacetate + 2-carbon acetyl CoA +H2O → citrate

catalyzed by citrate synthase

25
Q

step 2 of TCA cycle

A

citrate → isocitrate

catalyzed by aconitase

(because hydroxl group is not in proper location of oxidative decarboxylation)

26
Q

step 3 of TCA cycle

A

isocitrate + NAD+ → a-ketoglutarate + NADH + H+ + CO2

catalyzed by isocitrate dehydrogenase

(rate-limiting step) (first of 4 redox rxns)

(NAD+ → NADH)

27
Q

step 4 of TCA cycle

A

a-ketoglutarate + NAD+ + CoA → Succinyl CoA + NADH + H+ + CO2

via a-ketoglutarate dehydrogenase complex

28
Q

step 5 of TCA cycle

A

succinyl CoA + GDP ⇔ Succinate + GTP + CoA

catalyzed by succinyl CoA synthetase

29
Q

succinyl CoA contains a

A

high energy thioester bond

30
Q

succinyl CoA synthetase is the only step that yields

A

a high energy phopho-transfer compount (ATP or GTP) (substrate level phosphorylation)

31
Q

succinyl CoA synthetase isozymic forms:

  1. form that produces GTP is used in:
  2. form that produces ATP is used in:
A
  1. tissues that perform many anabolic reactions (liver)
  2. tissues that perofrm large amount of cellular respiration (skeletal and heart muscle)
32
Q

step 6 of TCA cycle

A

succinate + FAD → Fumarate + FADH2

catalyzed by succinate dehydrogenase

(FADH2 is not released from the enzyme, but electrons are passed directly to Co-Q in the ETC

33
Q

succinate dehydrogenase is located

A

in the inner mitochondrial membrane directly associated with ETC

34
Q

step 7 of TCA cycle

A

fumarate → L-malate

catalyzed by fumarase

35
Q

step 8 of TCA cycle

A

L-malate + NAD+ → Oxaloacetate + NADH + H+

catalyzed by malate dehydrogenase

36
Q

high [acetyl CoA] directly inhibits

A

PDH/PDC complex subunit E2

(pyruvate + NAD+ → acetyl CoA + NADH → TCA cycle)

37
Q

NADH inhibits

A

PDH/PDC complex subunit E3

(pyruvate + NAD+ → acetyl CoA + NADH → TCA cycle)

(ATP levels also inhibit PDH/PDC)

38
Q

high [pyruvate] and high [ADP] activate

A

PDH/PDC activity

39
Q

phosphatases are stimulated by

A

Ca2+ which increases to initiate muscle contraction

40
Q

insulin can stimulate

A

fatty acid synthesis by activating phosphatases and increasing the conversion of pyruvate to acetyl CoA (a precursor for fatty acids)

41
Q

activators of PDH/PDC

A

Ca2+, Mg2+ (via allosteric activation)

ADP, CoA, NAD+, pyruvate

insulin in adipose tissue, catecholamiens in cardiac muscle

42
Q

inhibitors of PDH/PDC

A

acetyl CoA, NADH

acetyl CoA, ATP

arsenite

43
Q

citrate synthase prevents

A

the wasteful hydrolysis of acetyl CoA

(first control site of TCA cycle)

44
Q

oxaloacetate binds to citrate synthase first, then the enzyme

A

undergoes configurational changes to accept acetyl CoA

45
Q

second control site of TCA cycle

A

isocitrate dehydrogenase

(allosterically stimulated by ADP) (NADH inhibits by directly displacing NAD+)

46
Q

third control site of TCA cycle

A

a-ketoglutarate dehydrogenase

(this complex is similar to PDH/PDC)

(allosterically inhibited by its products- succinyl CoA and NADH)

47
Q

buildup of citrate (due to regulation of isocitrate dehydrogenase) can be transported

A

to the cytosol and signal PFK to halt glycolysis

48
Q

a-ketoglutarate that builds up from enzyme inhibition can be used for

A

synthesis of amino acids and purine bases

49
Q

why is the TCA cycle anaplerotic

A

“fill up” rxns provide intermediates to replenish TCA cycle

50
Q

2 major anaplerotic reactions

  1. degradation of amino acids
  2. carboxylation of pyruvate
A
  1. degradation of amino acids:
  • Gln, Pro, His, Arg → replenishes a-ketoglutarate
  • Thr, Met, Ile, Val → replenishes succinyl CoA
  • Phe, Tyr, Asp → Fumurate
  1. carboxylation of pyruvate
    * pyruvate (ATP + PC) → replenishes oxaloacetate
51
Q

TCA cycle under fasting conditions

A

oxaloacetate → malate → gluconeogenesis → glucose

52
Q

when energy needs are met, TCA cycle intermediates are

A

drawn for biosynthesis of other molecules

(citrate leaves mitochondria and forms fatty acids and sterols)

(a-ketoglutarate → glutamate → other amino acids → purines)

(succinyl CoA → porphyrins, heme, chlorophyll)

(oxaloacetate → asparate → other amino acids, purines/pyrimidines)

53
Q

anaplerotic rxns are required during

A

states of low energy

Biochemistry (32 decks)

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