Lecture 21: Citric Acid Cycle

Question 1

Committed step

Answer 1

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

Question 2

Aerobic oxidation

Answer 2

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

Question 3

Citric acid cycle

Answer 3

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

Question 4

Compartmentation

Answer 4

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

Question 5

Oxidation of pyruvate to acetyl-CoA

Answer 5

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

Question 6

Coenzyme A

Answer 6

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

Question 7

Pyruvate dehydrogenase

Answer 7

Oxidizes pyruvate to acetyl-CoA

Question 8

Pantothenic acid

Answer 8

Vitamin B5

Question 9

Acetyl-CoA

Answer 9

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

Question 10

Pyruvate dehydrogenase phosphatase

Answer 10

Dephosphorylates PDH and activates PDH

Question 11

Pyruvate dehydrogenase kinase

Answer 11

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

Question 12

Step 1 of TCA: Citrate synthase

Answer 12

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

Question 13

Step 2 of TCA: Aconitate

Answer 13

Isomerization of citrate to isocitrate by dehydration-hydration

Question 14

Step 3 of TCA: Isocitrate dehydrogenase

Answer 14

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

Question 15

Step 4 of TCA: alpha-ketoglutarate dehydrogenase complex

Answer 15

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

Question 16

Step 5 of TCA: Succinyl-CoA synthetase

Answer 16

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

Question 17

Step 6 of TCA: Succinate dehydrogenase

Answer 17

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

Question 18

Coenzyme Q

Answer 18

Ubiquinone

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

Question 19

Step 7 of TCA: Fumarase

Answer 19

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

Question 20

Step 8 of TCA: Malate dehydrogenase

Answer 20

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

Question 21

TCA reducing elements

Answer 21

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

Question 22

Citrate accumulation

Answer 22

Inhibits phosphofructokinase

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

Question 23

Regulation of TCA

Answer 23

Allosteric feedback inhibition
Allosteric activation by ADP
Production inhibition

Question 24

Citric acid cycle intermediates

Answer 24

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

Question 25

Citrate

Answer 25

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

Question 26

Glutamate dehyrogenase

Answer 26

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

Question 27

Anaplerotic carboxylation

Answer 27

Conversion of pyruvate to oxaloacetate by pyruvate carboxylase

Question 28

Glucogenic

Answer 28

Metabolites that can be converted to glucose through gluconeogenesis

Question 29

Ketogenic

Answer 29

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

Question 30

Reciprocal regulation of pyruvate dehydrogenase and pyruvate carboxylase

Answer 30

Inhibition of pyruvate dehydrogenase

Activation of pyruvate carboxylase