1 24.1The Citric Acid Cycle Chapter 24 Metabolism and Energy Production

2 The citric acid cycle: Operates under aerobic conditions only. Oxidizes the two-carbon acetyl group in acetyl CoA to CO 2. Produces reduced coenzymes NADH and FADH 2 and one ATP directly. Citric Acid Cycle

3 Citric Acid Cycle Overview In the citric acid cycle: Acetyl (2C) bonds to oxaloacetate (4C) to form citrate (6C). Oxidation and decarboxylation convert citrate to oxaloacetate. Oxaloacetate bonds with another acetyl to repeat the cycle.

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5 Oxaloacetate combines with the two-carbon acetyl group to form citrate. Reaction 1 Formation of Citrate Citrate synthase

6 Reaction 2 Isomerization to Isocitrate Citrate isomerizes to isocitrate. The tertiary –OH group in citrate is converted to a secondary –OH that can be oxidized.

7 Summary of Reactions 1 and 2

8 Reaction 3 Oxidative Decarboxylation (1) A decarboxylation removes a carbon as CO 2 from isocitrate. The –OH group is oxidized to a ketone releasing H + and 2e - that form reduced coenzyme NADH.  -Ketoglutarate

9 In a second decarboxylation, a carbon is removed as CO 2 from  -ketoglutarate. The 4-carbon compound bonds to coenzyme A providing H + and 2e - to form NADH.  -Ketoglutarate Reaction 4 Oxidative Decarboxylation (2)  -Ketoglutarate dehydrogenase

10 Summary Reactions 3 and 4

11 Reaction 5 Hydrolysis The hydrolysis of the thioester bond releases energy to add phosphate to GDP and form GTP, a high energy compound.

12 In this oxidation, two H are removed from succinate to form a double bond in fumarate. FAD is reduced to FADH 2. Reaction 6 Dehydrogenation

13 Summary of Reactions 5 and 6

14 Reaction 7 Hydration of Fumarate Water is added to the double bond in fumarate to form malate.

15 Reaction 8 Dehydrogenation Another oxidation forms a C=O double bond. The hydrogens from the oxidation form NADH + H +.

16 Summary of Reactions 7 and 8

17 In the citric acid cycle: Oxaloacetate bonds with an acetyl group to form citrate. Two decarboxylations remove two carbons as 2CO 2. Four oxidations provide hydrogen for 3NADH and one FADH 2. A direct phosphorylation forms GTP. Summary of Products in the Citric Acid Cycle

18 Acetyl CoA + 3NAD + + FAD + GDP + P i + 2H 2 O 2CO 2 + 3NADH + 2H + + FADH 2 + HS-CoA + GTP Overall Chemical Reaction for the Citric Acid Cycle

19 Regulation of Citric Acid Cycle Low levels of ATP stimulate the formation of acetyl CoA for the citric acid cycle. High ATP and NADH levels decrease the formation of acetyl CoA and slow down the citric acid cycle.

20 The citric acid cycle: Increases its reaction rate when low levels of ATP or NAD + activate isocitrate dehydrogenase. Slows when high levels of ATP or NADH inhibit citrate synthetase (first step in cycle). Regulation of Citric Acid Cycle