Lecture 21: Citric Acid Cycle Flashcards

1
Q

Committed step

A

First irreversible reaction in a pathway who’s product cannot enter other pathways
Formation of fructose-1,6-bisphosphate

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2
Q

Aerobic oxidation

A

Mitochondrial conversion of pyruvate to acetyl-CoA and oxidation in TCA cycle

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3
Q

Citric acid cycle

A

TCA cycle, Krebs cycle
Oxidizes acetyl-CoA to CO2 and reduces NAD and FAD to NADH and FADH
No mitochondria, no TCA
Each round generates 3NADH, one GH2 and one GTP or ATP

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4
Q

Compartmentation

A

Allows additional regulation of metabolic pathways though regulation of their location/transport
Brings metabolites of one pathway into closer vicinity: faster reaction, less risk of unwanted side reactions

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5
Q

Oxidation of pyruvate to acetyl-CoA

A

Catalyses by pyruvate dehydrogenase
Requires NAD, TPP, FAD, CoA-SH and lipoic acid
Acetyl-CoA cannot be converted to glucose ever

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6
Q

Coenzyme A

A

Derivative of ADP: pantothenic acid linked to it via phosphate ester bond
Mercaptoethylamine is attached to pantothenic acid
Thiol group forms thioester bonds

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7
Q

Pyruvate dehydrogenase

A

Oxidizes pyruvate to acetyl-CoA

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8
Q

Pantothenic acid

A

Vitamin B5

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9
Q

Acetyl-CoA

A

Coenzyme A with a thioester bond to acetate
Thioester of coenzyme A and acetic acid
Oxidation in TCA cycle
Precursor for many larger metabolites

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10
Q

Pyruvate dehydrogenase phosphatase

A

Dephosphorylates PDH and activates PDH

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11
Q

Pyruvate dehydrogenase kinase

A

Phosphorylates PDH and inactivates PDH
Regulated allosterically:
Inactivated by acetyl CoA and activated by pyruvate and ADP

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12
Q

Step 1 of TCA: Citrate synthase

A

Condensation of oxaloacetate with acetyl-CoA to citrate, 2CO2 released
Irreversible
Product inhibition through citrate
Feedback inhibition by NADH and succinyl-CoA

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13
Q

Step 2 of TCA: Aconitate

A

Isomerization of citrate to isocitrate by dehydration-hydration

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14
Q

Step 3 of TCA: Isocitrate dehydrogenase

A

Oxidative decarboxylation of isocitrate to alpha-ketoglutarate
Irreversible
Redox reaction
Several forms of IDH: in many cancers, one of isoforms is mutated and works backwards

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15
Q

Step 4 of TCA: alpha-ketoglutarate dehydrogenase complex

A
Oxidative decarboxylation to succinyl-CoA
Similar to PDH complex
Irreversible reaction
Multi enzyme complex
Works in similar way as PDH
Thiamine as cofactor
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16
Q

Step 5 of TCA: Succinyl-CoA synthetase

A

Hydrolysis of CoA ester generates succinate and GTP (GTP can easily be converted to ATP)
Reversible
Succinate is a symmetrical molecule

17
Q

Step 6 of TCA: Succinate dehydrogenase

A

Reversible, redox
Succinate dehydrogenase generates ubiquinol
Fumarate formation
Reduces FAD to FADH2, deoxidation of FADH2 to Q: QH2

18
Q

Coenzyme Q

A

Ubiquinone

Accepts two electrons (H-) in stepwise manner to become ubiquinol

19
Q

Step 7 of TCA: Fumarase

A

Catalyzes hydration of fumarate to malate
Reversible
No change in oxidation state

20
Q

Step 8 of TCA: Malate dehydrogenase

A

Regenerates oxaloacetate from malate
Reversible reaction, redox
Different isoforms of malate dehydrogenase for mitochondrial and cytosolic enzyme
TCA is mitochondria and uses NAD to make NADH

21
Q

TCA reducing elements

A

NADH and FADH2 generated in the citric acid cycle are used to fuel ATP production in mitochondria
1NADH = 2.4 ATP
1FADH2 = 1QH2 = 1.5 ATP
The amount of ATP generates depends on efficiency of oxidative phosphorylation

22
Q

Citrate accumulation

A

Inhibits phosphofructokinase

Occurs when too much acetyl-CoA enters the TCA cycle and not enough NADH is used

23
Q

Regulation of TCA

A

Allosteric feedback inhibition
Allosteric activation by ADP
Production inhibition

24
Q

Citric acid cycle intermediates

A

Important precursors for many amino acids
Can enter gluconeogenesis through oxaloacetate
All citric acid cycle intermediates are glucogenic
More intermediates: more reactions can occur in parallel
Can be replenished

25
Q

Citrate

A

Intermediate in the conversion of acetyl-CoA to fatty acids and cholesterol

26
Q

Glutamate dehyrogenase

A

Catalyzes the reversible conversion of ketoglutarate and glutamate
Can be cataplerotic or anaplerotic

27
Q

Anaplerotic carboxylation

A

Conversion of pyruvate to oxaloacetate by pyruvate carboxylase

28
Q

Glucogenic

A

Metabolites that can be converted to glucose through gluconeogenesis

29
Q

Ketogenic

A

Metabolites that cannot be converted to glucose through gluconeogenesis
Acetyl-CoA

30
Q

Reciprocal regulation of pyruvate dehydrogenase and pyruvate carboxylase

A

Inhibition of pyruvate dehydrogenase

Activation of pyruvate carboxylase