Lecture 21: Citric Acid Cycle Flashcards Preview

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Flashcards in Lecture 21: Citric Acid Cycle Deck (30):
1

Committed step

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

2

Aerobic oxidation

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

3

Citric acid cycle

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

4

Compartmentation

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

5

Oxidation of pyruvate to acetyl-CoA

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

6

Coenzyme A

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

7

Pyruvate dehydrogenase

Oxidizes pyruvate to acetyl-CoA

8

Pantothenic acid

Vitamin B5

9

Acetyl-CoA

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

10

Pyruvate dehydrogenase phosphatase

Dephosphorylates PDH and activates PDH

11

Pyruvate dehydrogenase kinase

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

12

Step 1 of TCA: Citrate synthase

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

13

Step 2 of TCA: Aconitate

Isomerization of citrate to isocitrate by dehydration-hydration

14

Step 3 of TCA: Isocitrate dehydrogenase

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

15

Step 4 of TCA: alpha-ketoglutarate dehydrogenase complex

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

16

Step 5 of TCA: Succinyl-CoA synthetase

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

17

Step 6 of TCA: Succinate dehydrogenase

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

18

Coenzyme Q

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

19

Step 7 of TCA: Fumarase

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

20

Step 8 of TCA: Malate dehydrogenase

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

TCA reducing elements

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

Citrate accumulation

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

23

Regulation of TCA

Allosteric feedback inhibition
Allosteric activation by ADP
Production inhibition

24

Citric acid cycle intermediates

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

Citrate

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

26

Glutamate dehyrogenase

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

27

Anaplerotic carboxylation

Conversion of pyruvate to oxaloacetate by pyruvate carboxylase

28

Glucogenic

Metabolites that can be converted to glucose through gluconeogenesis

29

Ketogenic

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

30

Reciprocal regulation of pyruvate dehydrogenase and pyruvate carboxylase

Inhibition of pyruvate dehydrogenase
Activation of pyruvate carboxylase