Pyruvate Oxidationand the Krebs CycleCourtney, Chelsey, Morgan, GSchilbeG, Tessa

Pyruvate Oxidation

Pyruvate Oxidation

● Pyruvate is a glucose molecule cut in half● Pyruvate oxidation is the second stage of

cellular respiration● One step process occurring in

mitochondrial matrix● This is the end product of glycolysis

Pyruvate Oxidation (cont.)

● Can be derived from lactate taken up from the environment or multicellular organisms from other cells

● Produced from a variety of amino acids● Can be converted to acetyl coenzyme A● This conversion is irreversible● There are three changes to pyruvate

The Changes1. A CO2 portion is removed2. NAD+ is reduced by two Hydrogen atoms

obtained from food3. Coenzyme A is attached to the remaining

acetic acid portion

Activation

The pyruvate oxidation process starts off because a multienzyme complex catalyzes the following three changes.

Reactants and Products Equation: 2 pyruvate + 2 NAD+ + 2 CoA -> 2 acetyl-CoA + 2 NADH + 2 H+ +2 CO2

Reactants: 2 pyruvate, 2 NAD+, 2 CoAProducts: 2 acetyl-CoA, 2 NADH, 2 H+, 2 CO2

Converts Pyruvate/ pyruvic acid into Acetyl-CoAWhich takes places two times for every glucose molecule

Acetyl - CoA

● Used for lipid synthesis, animals cannot use to synthesize amino acids or carbohydrates

● This means that this conversion is an important step

● Removes the fully oxidized carbon while extracting some energy

● Prepares molecule for the remaining process

Reactions of the Pyruvate Dehydrogenase Complex

● First step: an oxidative decarboxylation reaction

● This is carried out by a very large enzyme complex called the pyruvate dehydrogenase complex (located in the mitochondrial matrix)

● This is irreversible and tightly regulatedPyruvate Dehydrogenase:2 pyruvate + 2 NAD+ + 2 CoA 2 acetyl-CoA + 2 NADH + 2 H+ +2 CO2

The Krebs Cycle

● step 3 in cellular respiration● 8 step, cyclic process● each step is catalyzed by a specific

enzyme● overall chemical equation for Krebs cycleoxaloacetate + acetyl-CoA + ADP + Pi + 3NAD+ + FAD

CoA + ATP + 3NADH + 3H+ + FADH2 + 2CO2 + oxaloacetate

The Krebs Cycle Diagram

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Krebs Cycle Steps● step 1: Acetic acid subunit of acetyl CoA is combined

with oxaloacetate to form molecule of citrate

● step 2:Citrate(6-C) is rearranged to isocitrate(6-C).

● step 3:Isocitrate (6-C) is converted to -ketoglutarate (5-C) by losing a CO2 and two hydrogen atoms that reduce NAD+to NADH.

● step 4:-ketoglutarate (5-C) is converted to succinyl-CoA (4-C). A CO2 is removed, coenzyme A is added, and two hydrogen atoms reduce NAD+ to NADH.

Krebs Cycle Steps● step 5:Succinyl CoA(4-C) is converted to succinate (4-

C). ATP is formed by substrate level phosphorylation, and coenzyme A is released.

● step 6: Succinate (4-C) is converted to fumarate (4-C). Two hydrogen atoms reduce FAD to FADH2.

● step 7: Fumarate (4-C) is converted to malate (4-C).

● step 8: Malate (4-C) is converted to oxaloacetate (4-C). Two hydrogen atoms reduce NAD+ to NADH.

Krebs Cycle

● original glucose molecule is entirely consumed● 6 carbon atoms leave process as 6 low-energy

CO2 molecules, which are disposed of as waste● original glucose molecule reduced to energy:

○ 4 ATP molecules2 from glycolysis2 from Krebs cycle

○ 12 reduced coenzymes2 NADH from glycolysis2 NADH from pyruvate oxidation6 NADH from Krebs cycle2 FADH2 from Krebs cycle

Reactants and Products

oxaloacetate + acetyl-CoA + ADP + Pi 3NAD+ + FAD CoA + ATP + 3NADH + 3H+ FADH2 + 2CO2 + oxaloacetate

Reactants: Acetyl Co-A, oxaloacetate, Citrate, Alpha ketoglutarate

Products: 6 NADH + H+, 2 FADH2, Carbon Dioxide, ATP

Krebs Cycle Simplified

Activation

● The Krebs cycle has to be carefully monitored to remain efficient

● Too fast: energy would be wasted producing ATP and reduced coenzymes

● Too slow: not enough energy released to support cell function

Activation Methods

● The Krebs cycle requires the products of pyruvate oxidation to start, so its rate can't surpass that stage's (substrate availability)

● Feedback inhibition is used for different stages○ NADH inhibits citrate synthase, isocitrate dehydrogenase and α-

ketoglutarate dehydrogenase○ succinyl-CoA competes with acetyl-CoA and inhibits α-ketoglutarate

dehydrogenase

Aerobic or Anaerobic

● Neither process uses O2 to function

● Both are still aerobic because their products (NADH and FADH2) move to the ETC which eventually uses O2(aerobic)

Sources● http://www.incolor.com/mcanaday/Krebs%20Phases.htm● http://wiki.pingry.org/u/ap-biology/index.php/Pyruvate_Oxidation_%

26_The_Citric_Acid_Cycle● http://course1.winona.edu/sberg/241f00/Lec-note/Respira.htm● http://www.livestrong.com/article/406081-why-is-the-krebs-cycle-an-

aerobic-process/● http://www.tamu.edu/faculty/bmiles/lectures/regulationtca.pdf● http://biochem.siu.

edu/bmb_courses/mbmb451b/lectures/mbmb451b_tcacycle.pdf● Nelson Biology 12, Chapter 2

Quiz

1. Pyruvate oxidation occurs in which of the following locations?

(a) cytoplasm

(c) inner mitochondrial membrane(b) mitochondrial matrix

Quiz

2. True or false CoA stands for Coenzyme A?

Answer: True

Quiz

3. How many pyruvate molecules does one glucose molecule yield after pyruvate oxidation?

Answer:Two

Quiz

4. What compound is both a reactant and a product in the Krebs cycle that makes it cyclic?

Answer: oxaloacetate

Quiz

5. Would you consider pyruvate oxidation aerobic or anaerobic?

Answer: aerobic

Quiz

6. What are all of glucose's carbons eventually released as during both processes?

Answer: CO2

Quiz

7. How many ATP are produced from the Krebs cycle?

Answer: 2

Quiz

8. Why is it important that the Krebs cycle doesn't proceed too slowly?

Answer: Not enough energy would be released to support cell function