TCA Cycle Flashcards

1
Q

where does the citric acid cycle?

A

in mito

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2
Q

the oxidation of 2 carbon units will produce?

A

2 CO2 molecules
1 GTP
high nrg e-‘s ( NADH, FADH2)

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3
Q

characteristics of acetyl CoA

A

active form of acetate

obtained from 2 nrg nutrients – carbs, lipids, proteins

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4
Q

formation of acetyl coA from pyruvate

A

decarboxylation
oxidation
transfer acetyl group to CoA

rxns are coupled to preserve nrg to drive formation of NADH and acetyl CoA

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5
Q

MPC

A

mitochondrial pyruvate carrier

pyruvate uses to get into mito for aerobic glycolysis

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6
Q

PDC

A

pyruvate dehydrogenase complex

catalyzes the decarboxylation of pyruvate

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7
Q

pyruvate dehydrogenase rxn

A

requires 3 enzymes
—-E1, E2, E3

5 coenzymes

  • –catalytic cofactors
    1. thiamine pyrophosphate
    2. lipoic acid
    3. FAD
  • –stoichiometric cofactors
    4. CoA
    5. NAD+

PDH links glycolysis to TCA

converts pyruvate to acetyl CoA

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8
Q

pyruvate dehydrogenase regulation

A

regulated by

  • -allosteric interactions
  • -reverse phosphorylation

high [acetyl coA] inhibits E2

  • products increase
  • phosphorylation of E2
  • accumulation of ADP and pyruvate activate phosphatases
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9
Q

the TCA occurs under ?

A

aerobic conditions

and produces more nrg from glucose than glycolysis

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10
Q

first step of TCA

A

condensation of 4-carbon oxaloacetate and 2-carbon acetyl group of acetyl coA

oxaloacetate reacts w/ acetyl coA + water = citrate and CoA

catalyzed by citrate synthase

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11
Q

citrate isomerizes …….

A

to isocitrate

hydroxyl group of citrate is not in proper location for oxidative decarboxylation

dehydra/hydration moves -OH via enzyme aconitase

intermediate product
cis-aconitase

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12
Q

aconitase

A

used to move the -OH group on citrate

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13
Q

isocitrate dehydrogenase

A

1st of 4 redox rxns

unstable intermediate = oxalosuccinate
—loses CO2 while bound to enzyme

**rate limiting step
isocitrate —-> a-ketoglutarate

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14
Q

a-ketoglutarate dehydrogenase

A

similar to pyruvate dehydrogenase

decarboxylate an a-ketoacid
and
creates a thioester linkage w/ CoA

rxn
a-ketoglutarate —> succinyl CoA

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15
Q

succinyl CoA synthetase

A

this is only step that directly yields a high nrg phosphor compound (GTP/ATP)

2 isozymic forms

  • –1. in liver, produce GTP
  • –2. in skeletal and heart muscles, produce ATP

rxn
succinyl CoA –> succinate

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16
Q

succinate dehydrogenase

A

catalyzes formation of fumarate while generating FADH2

located in inner mito memb - directly assoc w/ ETC

FADH2 is not released from enzyme but the e-‘s are passed to Co-Q in ETC

rxn
succinate —> fumarate

17
Q

fumarase

A

catalyzes the hydration of fumarate to form L-malate

fumarate –> L-Malate

18
Q

malate dehydrogenase

A

final step

  • -oxidation of malate has + G nrg
  • -enzyme specifically recognizes L-malate

rxn is driven by the consumption of its products

  1. oxaloacetate – by citrate synthase
  2. NADH – by ETC
19
Q

list the rxns of the TCA

A
  1. oxaloacetate —> citrate
  2. —> isocitrate
  3. —> a-ketoglutarate
  4. —> succinyl CoA
  5. —> succinate
  6. —> fumarate
  7. —> L-Malate
  8. —> oxaloacetate
20
Q

list the enzymes of TCA in order

A
citrate synthase
aconitase
isocitrate dehydrogenase
a-ketoglutarate dehydro
succinyl CoA synthetase
succinate dehydrogenase
fumarase
malate dehydrogenase
21
Q

list the byproducts of the rxns in the TCA

A
  1. H2O + S-CoA = CoA
  2. NAD+ = NADH + CO2 + H+
  3. NAD+ + CoA = NADH, CO2, H+
  4. GDP + Pi = GTP + CoA
  5. FAD = FADH2
  6. H2O in
  7. NAD+ = H+, NADH
22
Q

citric acid cycle regulation

A

high [acetyl coA] directly inhibits PDH complex subunit E2

nrg charge of cell dictates PDH complex activity
—high nrg = neg feedback

23
Q

TCA regulation – insulin

A

can stim fatty acid synthesis by activating phosphatases and increasing the conversion of pyruvate to acetyl CoA

which is the precursor for fatty acids

24
Q

TCA regulation – citrate synthase step

A

citrate synthase prevents wasteful hydrolysis of acetyl coA

oxaloacetate binds to the enzyme first, then the enzyme changes configuration to bind acetyl coA

25
Q

TCA regulation – isocitrate dehydrogenase step

A

allosterically stim by ADP
–enhances enzyme affinity for substrate

rxn product NADH also inhibits by directly displacing NAD+

control here leads to build up of citrate
which transports to cytosol
signals phosphofructokinase
glycolysis halts

26
Q

TCA - regulation – a-ketoglutarate dehydrogenase complex step

A

complex similar to PDH

similar to PDH in regulation
–allosterically inhibited by its products = succinyl coA and NADH

control causes a-ketoglutarate to build up from enzyme inhibition
–can then instead be used for synthesis of AA and purine bases

27
Q

why is TCA cycle Anaplerotic ?

A

Anaplerotic rxns provide intermediates for replenishing TCA cycle

2 major Anaplerotic rxns

  • –degradation of AA
  • –carboxylation of pyruvate
28
Q

TCA intermediates used in anabolic functions

A

when nrg needs are met by other means, intermediates are drawn for biosynthesis of other molecules in dif pathways

cycle will restart by formation of oxaloacetate from pyruvate when lactic acid builds up in muscle