7 REV 1406 Lecture

79
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CHAPTER 7 LECTURE SLIDES Prepared by Brenda Leady University of Toledo

Transcript of 7 REV 1406 Lecture

Page 1: 7 REV 1406 Lecture

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CHAPTER 7LECTURE

SLIDES

Prepared by

Brenda LeadyUniversity of Toledo

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Cellular respiration

Process by which living cells obtain energy from organic molecules and release waste products

Primary aim to make ATP and NADH Nutrients are broken down and re-arranged into

high energy molecules.

Metabolism: all the chemical processes of the body (cell)

When we breath we take in the oxygen needed for cellular respiration)

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Cellular respiration

Anaerobic respiration Without oxygen consumption.

Aerobic respiration uses oxygenO2 consumed and CO2 released

Focus on glucose but other organic molecules also used.

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Glucose metabolism

C6H12O6 + 6O2 → 6CO2 + 6H2O

ATP, NADH, FADH2

4 metabolic pathways

1. Glycolysis

2. Breakdown of pyruvate to an acetyl group

3. Citric acid cycle

4. Oxidative phosphorylation

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1

2 pyruvate

2 pyruvate

C C C C C C

C C C2

2

2 acetyl

C C C2

C C2

2 pyruvate

2 CO2

2 CO2

2 CO2

3

4 CO2

C C2

2 acetyl

Cytosol

2 NADH

2 NADH

+2 ATP

Via chemiosmosis

6 NADH 2 FADH2

Glycolysis:Glucose

Outer mitochondrialmembrane

Breakdown ofpyruvate:

2CO2 + 2acetyl

Citric acidcycle:

Via substrate-levelphosphorylation

Via substrate-levelphosphorylation

Mitochondrialmatrix

Inner mitochondrial membrane

+2 ATP +30–34 ATP

4 Oxidativephosphorylation:The oxidation of NADHand FADH2 via theelectron transportchain provides energyto make more ATPvia the ATP synthase.O2 is consumed.

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Stage 1: Glycolysis

Glycolysis can occur with or without oxygen.

Steps in glycolysis nearly identical in all living species

10 steps in 3 phases1. Energy investment (2 ATP)2. Cleavage3. Energy liberation

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3 phases of glycolysis1. Energy investment

Steps 1-3 2 ATP hydrolyzed to create fructose-1,6 bisphosphate

2. Cleavage Steps 4-5 6 carbon molecule broken into two 3 carbon molecules of

glyceraldehyde-3-phosphate3. Energy liberation

Steps 6-10 Two glyceraldehyde-3-phosphate molecules broken down into

two pyruvate molecules producing 2 NADH and 4 ATP Net yield in ATP of 2

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Glycolysis occurs in the cytosol

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C C C C C C

Glucose

OHH

HOHH

OH

O HH

HO

CH2OH

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ATP ATP

C C C C C C C C C C C C

Energy investment phase

Step 2 Step 3Step 1

GlucoseFructose-1,6-bisphosphate

OHH

HOHH

OH

O HH

HO

CH2OH

HHO

OH

OH

H

H

OCH2 PP O CH2O

Phase 1

2 ATP are hydrolyzed and the P- from the ATP is attached to the glucose

This phase raises the free energy level of the glucose which allows later Rxns to be exergonic.

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C CCATP

C C C C C C C C C C C C

C CC

Cleavage phase

Energy investment phase Step 4 Step 5

Step 2 Step 3Step 1

Glucose Fructose-1,6-bisphosphate

OHH

HOHH

OH

O HH

HO

CH2OH

ATPH

HO

OH

OH

H

H

OCH2 PP O CH2O

P

CHOH

C

H

O

CH2O

P

CHOH

H

OC

CH2O

Two molecules ofglyceraldehyde-3-phosphate

The cleavage phase (steps 4-5) breaks the six carbon molecule into 2 three carbon molecules

(glyceraldehyde-3-phsphate)

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C CC

Pi

ATP ATP

NADH ATP ATP

NADH ATP ATP

C C C C C C C C C C C C

C CC C CC

C CC

C O

C O

O–

CH3

C O

C O

O–

CH3

Cleavage phaseEnergy investment phase

Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Step 10

Energy liberation phaseSteps 6-10Liberates energy to produce energy intermediates

Step 2 Step 3Step 1

Glucose Fructose-1,6-bisphosphate

OHH

HOHH

OH

O HH

HO

CH2OH

HHO

OH

OH

H

H

OCH2 PP O CH2O

P

CHOH

C

H

O

CH2O

Pi

Two moleculesof pyruvate

P

CHOH

H

OC

CH2O

Two molecules ofglyceraldehyde-3-phosphate

Step 6, glyceraldehyde-3-phosphate is oxidized to yield NADH. (x2)Steps 7 and 10, 4 ATP are made by substrate level phosphorolation.

Glycolysis Net yield is 2 ATP and 2 NADH and

2 pyruvate molecules.

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ATP

OHH

HOHH

OH

O HH

HO

Glucose

CH2OH

Glycolysis

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ATP ADP

OHH

HOHH

OH

O HH

HO

OCH2P

Hexokinase

OHH

HOHH

OH

O HH

HO

Glucose

CH2OH

Glucose-6-phosphate

1. Glucose is phosphorylated by ATP.

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ATP ADPATP

Hexokinase

GlucoseOHH

HOHH

OH

O HH

HO

CH2OH

Glucose-6-phosphate

Phosphogluco–isomerase

Fructose-6-phosphateOHH

HOHH

OH

O HH

HO

OCH2P

HO

OH

OH

H

HH

OCH2P

CH2OHO

2. Glucose-6-phosphate is rearranged into fructose-6-phosphate

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ATP ADPATP ADP

Hexokinase Aldolase

- -OHH

HOHH

OH

O HH

HO

Glucose

CH2OH

Glucose-6-phosphate

Phosphogluco–isomerase

Fructose-6-phosphate

Phosphofructo–kinase

Fructose-1,6-bisphosphateOHH

HOHH

OH

O HH

HO

OCH2P

OH H

HOOH

HH

OCH2P

CH2OHO

HO

OH

OH

H

HH

OCH2P PCH2OO

3. Fructose-6-phosphate is phosphorylated to make fructose-1,6-bisphosphate (ATP is used)

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ATP ADPATP ADP

OHH

HOHH

OH

O HH

HO

OCH2P

Hexokinase Aldolase

- -

Isomerase

OHH

HOHH

OH

O HH

HO

Glucose

CH2OH

Glucose-6-phosphate

Phosphogluco–isomerase

Fructose-6-phosphate

Phosphofructo–kinase

Fructose-1,6-bisphosphate

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (X2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

HO

OH

OH

H

HH

OCH2P

CH2OHO

HO

OH

OH

H

HH

OCH2P PCH2OO

4. Fructose-1,6-bisphosphate is cleaved into Dihydroxyacetone and

Glyceraldehyde-3-phosphate

Dihydroxyacetone is isomerized into another glyceraldehyde-3-phosphate the result is 2 glyceraldehyde-3-phosphate

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Isomerase

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

5. The Dihydroxyacetone phosphateis Isomerized into Glyceraldehyde-3-phosphate.

(X2)

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2 NADH

2 NADH

6 NADH

GlucoseGlycolysis:

2

2

+2 ATP

2 pyruvate 2

2 FADH2

Break-down ofpyruvate

+2 ATP

Citric acidcycle

+30–34 ATP

Oxidativephosphorylation

ATP ADPATP ADP

OHH

HOHH

OH

O HH

HO

OCH2P

CO2

CO2

Hexokinase Aldolase

- -

Isomerase

OHH

HOHH

OH

O HH

HO

Glucose

CH2OH

Glucose-6-phosphate

Phosphogluco–isomerase

Fructose-6-phosphate

Phosphofructo–kinase

Fructose-1,6-bisphosphate

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (× 2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

CO2

HO

OH

OH

H

HH

OCH2P

CH2OHO

HO

OH

OH

H

HH

OCH2P PCH2OO

19

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Isomerase

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (× 2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

2 Pi

2 NAD+ +2 H+

2 NADH

Unstable phosphate bond

Glyceraldehyde-3-phosphatedehydrogenase

~

P

CHOH

OOCP

CH2O

1, 3 -bisphosphoglycerate( × 2 )

6. Glyceraldehyde-3-phosphate is oxidized to 1,3-

bisphosphoglycerate with the production of NADH

The phosphate group is destabilized making it ready for exergonic reaction

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2 ATP

Isomerase

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (× 2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

2 ADP

2 Pi

2 NAD+ +2 H+

2 NADH

Unstable phosphate bond

Glyceraldehyde-3-phosphatedehydrogenase

~

P

CHOH

OOCP

CH2O

1, 3 -bisphosphoglycerate( × 2 )

Phosphoglycero–kinase

P

CHOH

OC

O

CH2O

3-phosphoglycerate( × 2 )

7. A phosphate is removed from 1,3-bisphosphoglycerate to produce 3-phosphoglycerate.

The phosphate is transferred to ADP to make ATP. (x2, yield 2 ATP)

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2 ATP

Isomerase

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (× 2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

2 ADP

2 Pi

2 NAD+ +2 H+

PHCO

OC

O–

CH 2OH

2 NADH

Phosphoglycero–mutase

Unstable phosphate bond

Glyceraldehyde-3-phosphatedehydrogenase

~

P

CHOH

OOCP

CH2O

1, 3 -bisphosphoglycerate( × 2 )

Phosphoglycero–kinase

P

CHOH

OC

O

CH2O

3-phosphoglycerate( × 2 )

2-phosphoglycerate( × 2 )

8. The phosphate group is moved in 3-phosphoglycerate to form 2-phosphoglycerate

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2 ATP

Isomerase

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (× 2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

2 ADP

2 Pi

2 NAD+ +2 H+

PHCO

OC

O–

CH 2OH

~PCO

OC

O–

CH2

2 NADH

Phosphoglycero–mutase

Enolase

Unstable phosphate bondUnstable phosphate bond

Glyceraldehyde-3-phosphatedehydrogenase

~

P

CHOH

OOCP

CH2O

1, 3 -bisphosphoglycerate( × 2 )

Phosphoglycero–kinase

P

CHOH

OC

O

CH2O

3-phosphoglycerate( × 2 )

2-phosphoglycerate( × 2 )

2 H2O

Phosphoenolpyruvate( × 2 )

9. A water molecule is removed from 2-phosphoglycerate to form Phosphoenolpyruvate.

The phosphate group is destabilized in the process.

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2 ATP2 ATP

Isomerase

P

CHOH

H

C O

CH2O

Glyceraldehyde-3-phosphate (× 2)

Dihydroxyacetonephosphate

C O

OCH2P

CH2OH

2 ADP 2 ADP

2 Pi

2 NAD+ +2 H+

PHCO

OC

O–

CH 2OH

~PCO

OC

O–

CH2

OC

O–

CH3

OC

2 NADH

Phosphoglycero–mutase

Enolase Pyruvate kinase

Unstable phosphate bondUnstable phosphate bond

Glyceraldehyde-3-phosphatedehydrogenase

~

P

CHOH

OOCP

CH2O

1, 3 -bisphosphoglycerate( × 2 )

Phosphoglycero–kinase

P

CHOH

OC

O

CH2O

3-phosphoglycerate( × 2 )

2-phosphoglycerate( × 2 )

2 H2O

Phosphoenolpyruvate( × 2 )

Pyruvate( × 2 )

10. A phosphate is removed from Phosphoenolpyruvate to form Pyruvate.

The phosphate is transferred to ADP.

The end products of glycolysis is 2 pyruvate, 2 H+, 2 NADH, 2 ATP and 2 H2O

2 H2O

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Control of glycolyis Feedback inhibition occurs when ATP

concentrations in the cell are high.

ATP binds to the allosteric site in fructokinase preventing the action of this enzyme (step 3).

This prevents the further breakdown of glucose inhibiting the overproduction of ATP.

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Stage 2: Breakdown of pyruvate to an acetyl group In eukaryotes, pyruvate is transported to the

mitochondrial matrix Broken down by pyruvate dehydrogenase Molecule of CO2 removed from each pyruvate Remaining acetyl group attached to CoA to

make acetyl CoA 1 NADH is made for each pyruvate

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H+

OC

O–

CH3

OC

NADH+

NAD++ +CoA SH

CO2

Acetyl CoA

Outermembranechannel

H+/pyruvatesymporter

Pyruvatedehydrogenase

O

CoA

C

S

CH3

+

OC

O–

CH3

OC

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Pyruvate travels through a channel in the outer membrane and through an H+/pyruvate Symporter in the inner membrane to reach the matrix

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H+

OC

O–

CH3

OC

NADH+

NAD++ +CoA SH

CO2

Acetyl CoA

Outermembranechannel

H+/pyruvatesymporter

Pyruvatedehydrogenase

O

CoA

C

S

CH3

+

OC

O–

CH3

OC

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Pyruvate is oxidized to an acetyl group (CO2 and NADH is made).The acetyl group is transferred to a coenzyme-A Acetyl CoA

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Stage 3: Citric acid cycle(Acetyl CoA)

Metabolic cycleParticular molecules enter while others leave,

involving a series of organic molecules regenerated with each cycle

Acetyl is removed from Acetyl CoA and attached to oxaloacetate to form citrate or citric acid

Series of steps releases 2CO2, 1ATP, 3NADH, and 1 FADH2

Oxaloacetate is regenerated to start the cycle again

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Citric acid cycle

GTP

ATP

5

NADH

CO2

CO2

3

4

CCCCC

1

2

CCCC

NADH

8

CCCC7

CCCC

FADH2

6

CCCC

+2 ATP

2 CO2

2 NADH

2 NADH

6 NADH 2 FADH2

2 CO2

2 CO2

+2 ATP

2 pyruvate

CCCC

+30–34 ATP

CCCCCCCCCCCC

NADH

Acetyl CoA

Oxaloacetate

Citrate

Glycolysis:Glucose

Break-down ofpyruvate

Oxidativephosphorylation

O

C S CoAH2C

Citricacidcycle

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The citric acid cycle is “cyclic” because it involves a series of organic moleculesthat are regenerated after the turn of the cycle.

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Acetyl CoA

CoA—SH

C C

C C C C C C

COO–

CH2

C

CH2

COO–

COO–HO

CoA

C

S

O

CH+

Citrate

1

H2O

Citratesynthetase

2A

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1. An acetyl group from acetyl CoA is attached to oxaloacetate to form citrate

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Acetyl CoA

CoA—SH

C C

C C C C C C

C C C C C C

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

CoA

C

S

O

CH+

Citrate

Isocitrate

Aconitase

1

2B

H2O

Citratesynthetase

2A

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2. Citrate is rearranged to an isomer called isocitrate

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Acetyl CoA

CoA—SH

NAD+

NADH

C C

C C C C C C

C C C C C C C C C C C

CO2

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

COO–

CH2

CH2

C

COO–

O

+

CoA

C

S

O

CH+

Citrate

Isocitrate α-Ketoglutarate

Aconitase

1

2B

3

H2O

Citratesynthetase

2A

Isocitratedehydro-genase

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3. Isocitrate is oxidized to a-ketogluterate.(CO2 is released and NADH is formed)

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Acetyl CoA

CoA—SH

NAD+

NAD+

NADH

NADH

CoA—SH

C C

C C C C C C

C C C C C C C C C C C CO2

CO2

C C C C

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

COO–

CH2

CH2

C

COO–

O

+

COO–

CH2

CH2

C

S

O

CoA

+

CoA

C

S

O

CH+

Citrate

Isocitrate α-Ketoglutarate

Succinyl-CoA

Aconitase

1

2B

34

H2O

Citratesynthetase

2A

Isocitratedehydro-genase

α-Ketoglutaratedehydrogenase

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4. A-ketogluterate is oxidized as it combines with CoA to form succinyl CoA. (CO2 is released and NADH is formed)

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C C C C

ATPAcetyl CoA

CoA—SH

GTP

ADP

GDP + Pi

CoA—SH

NAD+

NAD+

NADH

NADH

CoA—SH

C C

C C C C C C

C C C C C C C C C C C CO2

CO2

C C C C

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

COO–

CH2

CH2

C

COO–

O

+

COO–

CH2

CH2

C

S

O

CoA

+

CoA

C

S

O

CH+

Citrate

Isocitrate α-Ketoglutarate

Succinyl-CoA

Aconitase

1

2B

34

H2O

Citratesynthetase

Succinyl-CoAsynthetase

2A

Isocitratedehydro-genase

α-Ketoglutaratedehydrogenase

COO–

COO–

CH2

CH2

Succinate

5

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5. Succinyl CoA is broken down to CoA and succinate.This drives the formation of GTP from GDP and P.(GTP can donate a phosphate to ADP to form ATP)

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ATPAcetyl CoA

CoA—SH

GTP

ADP

GDP + Pi

CoA—SH

NAD+

NAD+

NADH

NADH

CoA—SH

C C

C C C C C C

C C C C C C C C C C C CO2

CO2

C C C C

C C C C

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

COO–

CH2

CH2

C

COO–

O

+

COO–

CH2

CH2

C

S

O

CoA

+

COO–

COO–

CH

HC

CoA

C

S

O

CH+

Citrate

Isocitrate α-Ketoglutarate

Succinyl-CoA

Aconitase

Fumarase

Fumarate

1

2B

34

7

H2O

Citratesynthetase

Succinyl-CoAsynthetase

2A

Isocitratedehydro-genase

α-Ketoglutaratedehydrogenase

FADFADH2

C C C CCOO–

COO–

CH2

CH2

Succinate

Succinatedehydrogenase

6

5

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6. Succinate is oxidized to fumerate.(FADH2 is made)

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C C C C

ATPAcetyl CoA

CoA—SH

GTP

ADP

GDP + Pi

CoA—SH

NAD+

NAD+

NADH

NADH

CoA—SH

C C

C C C C C C

C C C C C C C C C C C CO2

CO2

C C C C

C C C CC C C C

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

COO–

CH2

CH2

C

COO–

O

+

COO–

CH2

CH2

C

S

O

CoA

+

COO–

COO–

CH

HC

COO–

COO–

CHHO

CH2

CoA

C

S

O

CH+

Citrate

Isocitrate α-Ketoglutarate

Succinyl-CoA

Aconitase

Fumarase

FumarateMalate

1

2B

34

78

H2O

Citratesynthetase

Succinyl-CoAsynthetase

H2O

2A

Isocitratedehydro-genase

α-Ketoglutaratedehydrogenase

FADFADH2

COO–

COO–

CH2

CH2

Succinate

Succinatedehydrogenase

6

5

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7. Fumerate combines with water to form malate.

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ATPAcetyl CoA

CoA—SH

GTP

ADP

GDP + Pi

CoA—SH

Citric acid cycle

NAD+

NADH

NAD+

NAD+

NADH

NADH

CoA—SH

C C

C C C C C C

C C C C C C C C C C C CO2

CO2

C C C C

C C C CC C C C

C C C C

COO–

CH2

C

CH2

COO–

COO–HO

COO–

CH2

HC

CHHO

COO–

COO–

COO–

CH2

CH2

C

COO–

O

+

COO–

CH2

CH2

C

S

O

CoA

+

COO–

COO–

CH

HC

COO–

COO–

CHHO

CH2

COO–

COO–

CO

CH2

CoA

C

S

O

CH+

Citrate

Isocitrate α-Ketoglutarate

Succinyl-CoA

Aconitase

Fumarase

FumarateMalate

Oxaloacetate

1

2B

34

78

H2O

Citratesynthetase

Succinyl-CoAsynthetase

H2O

2A

Isocitratedehydro-genase

α-Ketoglutaratedehydrogenase

Malatedehydro-genase

FADFADH2

C C C CCOO–

COO–

CH2

CH2

Succinate

Succinatedehydrogenase

6

5

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Malate is oxidized to Oxaloacetate.(the cycle can begin again)

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Control of the citric acid cycle Competitive inhibition

Oxaloacitate is a competitive inhibitor of succinate dehydrogenase (catalizes step 6)

When the oxaloacitate level becomes too high, succinate dehydrogenase is inhibited and the citric acid cycle slows down.

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On to the oxidative phosphorylation

Up to this point we have yielded 6 molecules of CO2, 4 molecules of ATP, 10 molecules of NADH and 2 molecules of FADH2

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Stage 4: Oxidative phosphorylation

High energy electrons are removed from NADH and FADH2 to make ATP

Typically requires oxygen Oxidative process involves electron

transport chain Phosphorylation occurs by ATP synthase

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Oxidation: ETC

Electron transport chains (ETC) Is a Group of protein and small organic molecules

embedded in the inner mitochondrial membrane

These proteins and molecules can accept and donate electrons in a linear manner in a series of redox reactions.

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Electrons are transferred to components with increasing electronegativity.

The end of the line is Oxygen which is the most electronegative. (final electron acceptor)

Movement of these electrons generates a H+ (proton) electrochemical gradient/ proton-motive force The transfer of the electrons is highly exergonic

and free energy can be harnessed to pump H+ across the inner mitochondrial membrane creating a proton electrochemical gradient.

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The hydrogens (protons) flow through an enzyme (ATP Synthase) down its concentration gradient.

ATP Synthase harnesses free energy from the flow of protons to attach phosphates to ADP generating ATP.

Kinetic energy of the H+ gradient is converted to chemical bond energy of ATP

This process is called chemiosmosis.

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45

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

NAD+

c

I

III

II

IV

H2O

Q

Matrix

+

NADH dehydrogenase

Ubiquinone

Cytochrome b-c1

Cytochrome c

Cytochrome oxidase

ATP synthase

Succinatereductase

Inner mitochondrialmembrane

ATPsynthesis

Electrontransportchain

Intermembranespace

movement

e– movement

KEYH+

NADH

FAD + 2

H+

H+H+

H+

H+

H+

H+

H+

H+

H+

H+H+

H+

H+

H+

H+

H+

H- -

FADH2

ADP + Pi

H+

2 H+ + ½ O2

ATP

MatrixIntermembranespaceMembrane proteins

and components accept and Transfer e- in a highly Exergonic Rxn. Which is used to drive H+ against its Concentration gradient.

The flow of H+ through theATP synthase enzyme provides free energy for the phosphorolation of ADP to ATP.

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Phosphorylation by ATP synthase

Lipid bilayer of inner mitochondrial membrane relatively impermeable to H+

H+ can only pass through ATP synthase Harnesses the free energy release to

synthesize ATP from ADP Chemiosmosis - chemical synthesis of ATP

as a result of pushing H + across a membrane

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47

NADH oxidation and ATP synthesis Oxidation of NADH and FADH results in

electrochemical gradient used to synthesize ATP (FADH donates H+ to the succinate reductase enzyme)

30-34 ATP molecules per glucose molecule broken down into CO2 and H2O

Rarely achieve maximal amountNADH used in anabolic pathwaysH+ gradient used for other purposes

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ATP synthase

Enzyme Energy conversion- H+ electrochemical

gradient or proton motive force converted to chemical bond energy in ATP

Racker and Stoeckenius confirmed ATP uses an H+ electrochemical gradient

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YIELDS

Glycolyis: 2 ATP

Citric Acid Cycle: 2 ATP

Oxidative Phosphorylation: 30-34 ATP

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ATP synthase

A Rotary machine that makes ATP as it spins

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51

ATP synthase

Vesicle

Bacteriorhodopsin(light-driven H+ pump)

ADPPi

No H+ gradient

Light rays

H+ gradient

ATP

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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52

H+

a

b

cc

c

H+

Matrix

Intermembranespace

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

ATPADP + PiH+ passes through the c unitCausing the Y unit to rotateClockwise. Each 120 deg. turnCauses a conformational changeThat attaches P to ADP.

Conf. 1: ADP and P bindConf. 2: ADP and P are bondedConf 3: ATP is released

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Chemicals can inhibit e- flow along ETC

Cyanide: inhibits cytochrome oxidase

This shuts down the ETC preventing cells from making enough ATP for survival

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Yoshida and Kinosita deomonstrate that the γ subunit of the ATP synthase spins

Masasuke Yoshida, Kazuhiko Kinosita, and colleagues set out to experimentally visualize the rotary nature of the ATP synthase

Released membrane embedded portion and adhered it to a slide

Visualize γ subunit using fluorescence Added ATP to make reaction run backward Rotated counterclockwise to hydrolyze ATP

Rotate clockwise to synthesize ATP

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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Experimental level Conceptual level

No ATP added

ATP Rotation

ATP added

No rotation observed.

Rotation was observed as shown below. This is a time-lapse view of the rotation in action.

Control:

Linker proteins

33 complex

Slide

+ ATP: counterclockwiserotation

Fluorescencemicroscope

Fluorescentactinfilament

ATPATP

Add linker proteinsand fluorescentactin filaments.

Add purifiedcomplex.

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Cancer cells usually favor glycolysis Many disease associated with alterations in

carbohydrate metabolism Warburg effect- cancer cells preferentially use

glycolysis while decreasing oxidative phosphorylation Used to diagnose cancers in PET scans Glycolytic enzymes overexpressed in 80% of all types

of cancers Caused by genetic and environmental factors-

mutations and low oxygen

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58

Other organic molecules

Focus on glucose but other carbohydrates, proteins and fats also used for energy

Enter into glycolysis or citric acid cycle at different points

Utilizing the same pathways for breakdown increases efficiency

Metabolism can also be used to make other molecules (anabolism)

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Amino Acids and Fats

Can enter the later stages of glycolysis, the citric acid cycle or at different points along the pathway after being modified.

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Amino Acids and Fats

Some breakdown products of proteins enter into the later stages of glycolysis or enter the citric acid cycle.

Ex. Acetyl groups from some amino acids can be removed and attached to CoA to become Acetyl CoA which enters the citric acid cycle.

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Amino Acids and Fats

Fats can be broken down to glycerol and 2 fatty acids (acyls).

Glycerol can be modified into glyceraldehyde-3-phosphate and enter glycolysis at step 5.

The 2 fatty acetyl tails can be removed and combined with CoA Acetyl-CoA then enter the citric acid cycle

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Amino Acids and Fats

After modification proteins and fats use the same enzymes and pathways.

By using the same pathways and enzymes cellular metabolism is more efficient

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63

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Proteins Carbohydrates Fats

Sugars

Pyruvate

Acetyl CoA

Aminoacids

Glycolysis:Glucose

Glyceraldehyde-3-phosphate

Citricacidcycle

Oxidativephosphorylation

Glycerol Fattyacids

© The McGraw-Hill Companies, Inc./Ernie Friedlander/Cole Group/Getty Images

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7.3 Anaerobic metabolism

For environments that lack oxygen or during oxygen deficits

2 strategies

1. Use substance other than O2 as final electron acceptor in electron transport chain

2. Produce ATP only via substrate-level phosphorylation

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Other acceptors

E. coli uses nitrate (NO3

-) under anaerobic conditions

Makes ATP via chemiosmosis even under anaerobic conditions

Nitrate is the final acceptor instead of O2

65

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

NADH

NAD+ +

Ubiquinone

Cytochrome b

Nitrate reductase

ATP

ATP synthase

Cytoplasm

NADH dehydrogenase

H+

Extracellularfluid

+ PiADP

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

NO2– + H2O

NO3– + 2 H+

H+ movement

KE Y

e– movement

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Fermentation : Breakdown of organic molecules to produce energy without oxygen.

Many organisms can only use O2 as final electron acceptor

Make ATP via glycolysis only:

The problem: Glycolysis needs NAD (to continue) and generates NADH NADH produces free radicals in high concentrations We need to reduce the NADH to NAD

66

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The solution

Muscle cells produce lactate (lactic acid) The pyruvate is converted to lactate.

The electrons to reduce pyruvate to lactate are derived from oxidation of NADH which produces NAD.

Once oxygen is restored the lactate is converted back to pyruvate for energy or may be converted to glucose by the liver.

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Yeast cells make ethanol

The pyruvate is broken down to CO2 and acetaldhyde.

The acetaldehyde is reduced to ethanol by oxidation of NADH to NAD

Fermentation produces far less ATP (2 ATP per

glucose molecule) than oxidative phosphorylation (34-38 ATP).

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69

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

(a) Production of lactic acid (b) Production of ethanol

2 lactate (secreted from the cell)

2 H1

2 NAD+ + 2 H+ 2 NADH

2 ATP

2 ethanol (secreted from the cell) 2 acetaldehyde

2 H+

2 pyruvate

2 NAD+ + 2 H+ 2 NADH

GlycolysisGlucose

2 pyruvate

2 ATP

GlycolysisGlucose

O

OC

O—

C

CH3

O

H OHC

C

O—

CH3

+ 2 Pi2 ADP

O

OC

O—

C

CH3

2 CO2

H OHC

H

CH3

OC

H

CH3

(weights): © Bill Aron/Photo Edit; (wine barrels): © Jeff Greenberg/The Image Works

+ 2 Pi2 ADP

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END HERE

SKIP SECTION 7.3

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71

Secondary Metabolism

Primary metabolism- essential for cell structure and function

Secondary metabolism- synthesis of secondary metabolites that are not necessary for cell structure and growth

Secondary metabolites unique to a species or group

Roles in defense, attraction, protection, competition

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4 categories

Phenolics Antioxidants with intense flavors and smells

Alkaloids Bitter-tasting molecules for defense

Terpenoids Intense smells and colors

Polyketides Chemical weapons

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1. Identify the 4 steps of glucose metabolism. 2. What is the purpose for changing

glucose into fructose1,6 bisphosphate? 3. Where do the Phosphates come from

for the above reaction?

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4. The citric acid cycle is controlled by

____________. 5. The equation, C6H12O6+ 6O2 6CO2+ 6H2O (ATP + Heat), describes which

of the following processes?  A.  photosynthesis B.  cell respiration C.  cell fermentation D.  glycolysis E.  anaerobic metabolism

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6.What is produced from pyruvate in muscle cells under anaerobic conditions?

Which of the following processes will occur in the presence or absence of oxygen?  A.  glycolysis B.  electron transport chain C.  oxidative phosphorylation D.  cellular respiration E.  citric acid cycle