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
step 2 of TCA cycle
**citrate** → **isocitrate** catalyzed by aconitase (because hydroxl group is not in proper location of oxidative decarboxylation)
26
step 3 of TCA cycle
**isocitrate** + NAD+ → **a-ketoglutarate** + **NADH** + H+ + **CO2** catalyzed by isocitrate dehydrogenase (rate-limiting step) (first of 4 redox rxns) (NAD+ → NADH)
27
step 4 of TCA cycle
**a-ketoglutarate** + NAD+ + CoA → **Succinyl CoA** + **NADH** + H+ + **CO2** via a-ketoglutarate dehydrogenase complex
28
step 5 of TCA cycle
**succinyl CoA** + GDP ⇔ **Succinate** + **GTP** + CoA catalyzed by succinyl CoA synthetase
29
succinyl CoA contains a
high energy thioester bond
30
succinyl CoA synthetase is the only step that yields
a high energy phopho-transfer compount (ATP or **GTP**) (substrate level phosphorylation)
31
succinyl CoA synthetase isozymic forms: 1. form that produces GTP is used in: 2. form that produces ATP is used in:
1. tissues that perform many anabolic reactions (liver) 2. tissues that perofrm large amount of cellular respiration (skeletal and heart muscle)
32
step 6 of TCA cycle
**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
succinate dehydrogenase is located
in the inner mitochondrial membrane directly associated with ETC
34
step 7 of TCA cycle
**fumarate** → **L-malate** catalyzed by fumarase
35
step 8 of TCA cycle
**L-malate** + NAD+ → **Oxaloacetate** + **NADH** + H+ catalyzed by malate dehydrogenase
36
high [acetyl CoA] directly inhibits
PDH/PDC complex subunit E2 (**pyruvate** + NAD+ → **acetyl CoA** + NADH → **TCA cycle**)
37
NADH inhibits
PDH/PDC complex subunit E3 (**pyruvate** + NAD+ → **acetyl CoA** + **NADH** → TCA cycle) (ATP levels also inhibit PDH/PDC)
38
high [pyruvate] and high [ADP] activate
PDH/PDC activity
39
phosphatases are stimulated by
Ca2+ which increases to initiate muscle contraction
40
insulin can stimulate
fatty acid synthesis by activating phosphatases and increasing the conversion of pyruvate to acetyl CoA (a precursor for fatty acids)
41
activators of PDH/PDC
Ca2+, Mg2+ (via allosteric activation) ADP, CoA, NAD+, pyruvate insulin in adipose tissue, catecholamiens in cardiac muscle
42
inhibitors of PDH/PDC
acetyl CoA, NADH acetyl CoA, ATP arsenite
43
citrate synthase prevents
the wasteful hydrolysis of acetyl CoA (first control site of TCA cycle)
44
oxaloacetate binds to citrate synthase first, then the enzyme
undergoes configurational changes to accept acetyl CoA
45
second control site of TCA cycle
isocitrate dehydrogenase (allosterically stimulated by ADP) (NADH inhibits by directly displacing NAD+)
46
third control site of TCA cycle
a-ketoglutarate dehydrogenase (this complex is similar to PDH/PDC) (allosterically inhibited by its products- succinyl CoA and NADH)
47
buildup of citrate (due to regulation of isocitrate dehydrogenase) can be transported
to the cytosol and signal PFK to halt glycolysis
48
a-ketoglutarate that builds up from enzyme inhibition can be used for
synthesis of amino acids and purine bases
49
why is the TCA cycle anaplerotic
"fill up" rxns provide intermediates to replenish TCA cycle
50
2 major anaplerotic reactions 1. degradation of amino acids 2. carboxylation of pyruvate
1. degradation of amino acids: * Gln, Pro, His, Arg → replenishes a-ketoglutarate * Thr, Met, Ile, Val → replenishes succinyl CoA * Phe, Tyr, Asp → Fumurate 2. carboxylation of pyruvate * pyruvate (ATP + PC) → replenishes oxaloacetate
51
TCA cycle under fasting conditions
oxaloacetate → malate → gluconeogenesis → glucose
52
when energy needs are met, TCA cycle intermediates are
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
anaplerotic rxns are required during
states of low energy