Presentation is loading. Please wait.

Presentation is loading. Please wait.

BC368: Biochemistry of the Cell II Citric Acid Cycle Chapter 16 March 12, 2015.

Similar presentations


Presentation on theme: "BC368: Biochemistry of the Cell II Citric Acid Cycle Chapter 16 March 12, 2015."— Presentation transcript:

1 BC368: Biochemistry of the Cell II Citric Acid Cycle Chapter 16 March 12, 2015

2 3 stages of respiration  Production of acetyl-CoA (e.g., during glycolysis and the bridging reaction)  Oxidation of acetyl-CoA via the citric acid cycle  Electon transport and oxidative phosphorylation to produce lots of ATP Fig 16-1

3  Glycolysis takes place in the cytosol  The citric acid cycle takes place in the mitochondrial matrix Mitochondrial Architecture

4 The Bridging Reaction H + +

5 The Bridging Reaction Fig 16-2

6 The Bridging Reaction  E 1 : orange  E 2 : green  E 3 : yellow

7 Fig 16-6 Pyruvate dehydrogenase complex 1. Decarboxylation2. Oxidation 3. Acetyl group to CoA4. Restore enzyme Fig 16-6

8 Pyruvate dehydrogenase complex Fig 16-6 Step 1. Decarboxylation

9 Step 1: Decarboxylation  TPP is derived from vitamin B1  Common for decarboxylation reactions  Carries carbon groups transiently Fig 14-15

10 Fig 16-6 Pyruvate dehydrogenase complex Fig 16-6 Step 2. Oxidation, with reduction of E 2

11 Step 2: Oxidation  Hydroxyethyl group is oxidized to acetyl group, transferred to lipoamide of E2, which is reduced.

12 of interest here Lipoic Acid “Swinging Arm”  Swinging arm acyl group carrier  Transfers intermediates between different enzyme sites

13 The Marsh Test

14 Fig 16-6 Pyruvate dehydrogenase complex Fig 16-6 Step 3. Transfer to CoA

15 Step 3: Transfer to CoA  Acetyl group is transferred to coenzyme A by E2.

16 Coenzyme A  Derived from Vitamin B5 (pantothenic acid)  “Activates” the acetyl group Fig 16-3

17 Fig 16-6 Pyruvate dehydrogenase complex Fig 16-6 Step 4. Restoring the enzyme

18 Fig 16-6 Step 4: Restoring the enzyme  FAD of E3 reoxidizes dihydrolipoamide.  NAD + reoxidizes FADH 2.

19 FAD/FADH 2  Derived from Vitamin B2 (riboflavin)  1 or 2 electron acceptor

20 NAD + /NADH  Derived from Vitamin B3 (niacin)  2 electron acceptor

21 Fig 16-6 Pyruvate dehydrogenase complex Fig 16-6

22 Coenzyme A Acetyl group is activated in two ways:  Carbonyl carbon is activated for attack by nucleophiles  Methyl carbon is more acidic Fig 16-3

23 The Citric Acid Cycle

24

25 Reaction 1: Condensation

26 Citrate synthase mechanism Fig 16-9 1. deprotonation of methyl group of acetyl-CoA

27 2. enolate attacks carbonyl of OA, forming citroyl-CoA Citrate synthase mechanism Fig 16-9

28 3. hydrolysis of thioester releases citrate and CoA Citrate synthase mechanism Fig 16-9

29 Reaction 2: Isomerization

30 A symmetric molecule that acts asymmetric! Chemically, these carbons are identical!

31 A symmetric molecule that acts asymmetric! Chemically, these carbons are identical! So both these products should be formed

32 A symmetric molecule that acts asymmetric! Chemically, these carbons are identical! So both these products should be formed

33 Prochiral molecules can act chiral!

34 Reaction 3: Oxidative Decarboxylation

35 Reaction 4: Oxidative Decarboxylation

36 Reaction 5: Substrate-level phosphorylation

37 Succinyl-CoA synthetase reaction  Hydrolysis of CoA-SH drives phosphorylation of succinate within the enzyme-substrate complex  Succinate transfers its phosphate group to the enzyme  Enzyme phosphorylates GDP

38 Reactions 6, 7, and 8  Oxidation  Hydration  Oxidation

39 Summary of TCA Fig 16-14

40 Regulation  Irreversible reactions are regulated  In general, energy charge is key: AMP/NAD + activate ATP/NADH inhibit  Product inhibition Fig 16-19

41 Anaplerotic Reactions Fig 16-16

42 Anaplerotic Reactions  Example: pyruvate carboxylase, which uses a biotin (vitamin B7) cofactor to carry CO 2

43 Daniel plans to enter the Mr. Colby contest and wants to get jacked. He has begun adding raw eggs to his diet and is up to a dozen a day. Unfortunately, he has been experiencing lactic acidosis during his weight training and hypoglycemia between meals. What’s up with Daniel? Case Study

44 K D ≈ 10 -15 M Case Study

45 Pyruvate carboxylase Carboxyl group of bicarbonate is “activated” by phosphorylation

46 Pyruvate carboxylase “Activated” CO 2 is passed to biotin cofactor with loss of Pi

47 Pyruvate carboxylase CO 2 is passed to second active site for rxn with pyruvate

48 CO 2 is released for reaction with pyruvate to form OA. Pyruvate carboxylase

49 Glyoxylate cycle Fig 16-22  Plants and some microorganisms can convert acetyl-CoA to oxaloacetate for net gain of carbon and net synthesis of TCA intermediates

50 Intersection with TCA Fig 16-24  Glyxoylate pathway runs simultaneously with TCA but in a different compartment.

51 Coordinated regulation Fig 16-25  Isocitrate is a branch point; its fate depends on relative activities of isocitrate dehydrogenase (TCA) and isocitrate lyase (glyoxylate cycle).

52 Vania can’t believe that she feels so lousy. Even though it is St. Patrick’s Day weekend and she’s been up all night partying, she’s never felt this bad before. Her head is pounding, and she feels tired, weak, dizzy, and sick to her stomach. She would drink some water, but she lost her Nalgene bottle last week somewhere, and the walk to the dining hall is just way too far. Case Study 1. What is wrong with Vania? 2. What are the consequences of dehydration on metabolism? 3. What are the metabolic breakdown products of ethanol? 4. What role do these metabolic products play in the citric acid cycle? 5. What would you recommend to Vania?


Download ppt "BC368: Biochemistry of the Cell II Citric Acid Cycle Chapter 16 March 12, 2015."

Similar presentations


Ads by Google