1 Metabolism Metabolic Pathways 160712

7/31/2019 1 Metabolism Metabolic Pathways 160712

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Metabolism(The Acquisition and Utilization of Free Energy)

Catabolism: exergonic oxidation

Anabolism: endergonic processes


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(Oxidation)

(Biosynthesis)

(Exergonic)

(Endergonic)


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Function of ATP

Cells make use of ATP for:

Chemical workATP supplies energy tosynthesize macromolecules, and therefore theorganism

Transport workATP supplies energy needed to

pump substances across the plasma membrane Mechanical workATP supplies energy for

cellular movements


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Redox Reactions


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The electron transfer reaction:

NAD+ + 2e + H+ NADH.

It may also be written as:

NAD+ + 2e + 2H+ NADH + H+

N

R

H

C

NH2

O

N

R

C

NH2

OH H

+2e

+H

+

NAD+

NADH

NAD (Nicotinamide Adenine Dinucleotide)Electron transfer from NADH providesfree energy

(NAD+/NADH)


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FAD accepts 2e+ 2H+ in going to its reduced state:

FAD + 2e + 2H+

FADH2

C

C

C

H

C

C

H

C

N

C

C

N

N

C

NH

C

H3C

H3C

O

O

CH2

HC

HC

HC

H2C

OH

OPOPO

O

O-

O

O-

Ribose

OH

OH

Adenine

C

C

C

H

C

C

H

C

N

C

C

H

N

N

H

C

NH

C

H3C

H3C

O

O

CH2

HC

HC

HC

H2C

OH

OPOPO

O

O-

O

O-

Ribose

OH

OH

AdenineFA FAD

2e

+2H+

dimethylisoalloxazin

FAD (Flavin Adenine Dinucleotide)


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Metabolic Networks

Reactions:

Pathways:

Networks:

A B

A B C D

A B C E

D


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Metabolic Pathways

A> B


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Metabolic Pathways

A> B > C > D > E


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Metabolic Pathways

A> B > C > D > E

F > G > H


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Metabolic Pathways

A> B > C > D > E

F > G > H

e2e1

e5

e4

e6 e7

e3


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Metabolic Pathways

A> B > C > D > E

F > G > H

e2e1

e5

e4

e6 e7

e3


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Metabolic Pathways

A> B > C > D > E

F > G > H

e2e1

e5

e4

e6 e7

S

PCell membrane

e3


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Properties of Metabolic Pathways

Irreversible (overall): reversibility of individualsteps

Separate Anabolic and Catabolic Pathways First Committed (Exergonic) Step: others

close to equilibrium

Regulation (usually first committed step):

often rate-limiting Compartamentation: transport


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Feedback inhibition

Enzyme modulators

No enzyme

Enzyme isolation Energy availability - ATP

Control of Metabolic Pathways


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Example of Metabolic Regulation


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A Summary of the Pathways of Catabolism and Anabolism

C t b li Th B kd f M t i t


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Catabolism: The Breakdown of Macro-nutrients


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Glycolysis

Phosphorylation

Pyruvate Anaerobic respiration

Lactate production

2 ATPs produced

Energy Production

ATP

Overview of aerobic pathways for ATP Production


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Glycolysis

Event 1 - Phosphorylation

two phosphates

added to glucose

requires ATP

Event 2Splitting (cleavage)

6-carbon glucose split

into two 3-carbon

molecules

4-14


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Glycolysis

Event 3Production of NADH and

ATP

hydrogen atoms are released

hydrogen atoms bind to NAD

+

toproduce NADH

NADH delivers hydrogen atoms

to electron transport chain if

oxygen is available

ADP is phosphorylated tobecome ATP

two molecules of pyruvic acid

are produced

4-15


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Glycolysis Summary

Inputs:

Glucose

2 NAD+ 2 ATP

4 ADP + 2 P

Outputs:

2 pyruvate

2 NADH 4 ADP

2 ATP (net gain)


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Anaerobic Reactions

If oxygen is not available -

electron transport chaincannot accept NADH

pyruvic acid is converted to

lactic acid

glycolysis is inhibited

ATP production declines

4-16


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Fermentation

In the absence of oxygen, the end-product

of glycolysis, pyruvate, is used in

fermentation.During glycolysis, all the NAD+ becomes

saturated with electrons (NADH). When this

happens, glycolysis will stop.

2 NADH and 2 ATP produced.

Pyruvate is used as the electron acceptor

resetting the NAD+ for use in glycolysis.


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Fermentation2 Types

Animals add extracted

electrons to pyruvate

forming lactate.

Reversible when oxygen

becomes available.

Muscle fatigue

Yeasts, single-celled fungi,

produce ethanol.

Present in wine & beer.

Alcoholic fermentation


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Pyruvate

Ethanol

+

lactate

+

acetate

+

succinate

+

carbon dioxide

+ hydrogen

+

formate

Ethanol

+ 2,3-butanediol +

formate

+

lactate

+

carbon dioxide

+

hydrogen

Lacta

te

Ethanol

+

carbon

dioxide

Propiona

te +

carbon dioxide

+ hydrogen +

acetate

Butyrate

+

butanol

+ isopropanol +

acetone

+

carbon dioxide

fermentation

Escherichia Enterobacter Lactobacillus Saccharomyces Propioni-bacterium Clostridium


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Glycolysis takes place in the cytoplasm of almost all cells.


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Aerobic Reactions

If oxygen is available

pyruvic acid is used to produce

acetyl CoA

citric acid cycle begins

electron transport chain functions

carbon dioxide and water are formed

36 molecules of ATP produced perglucose molecule

4-17

Citric Acid Cycle


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Citric Acid Cycle


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Citric acid cycle


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Citric acid cycle inputs and outputs

per glucose molecule

Inputs:

2 acetyl groups

6 NAD+

2 FAD

2 ADP + 2 P

Outputs:

4 CO2

6 NADH

2 FADH2

2 ATP


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Aerobic Respiration

In aerobic respiration, ATP forms as electrons

are harvested, transferred along the electron

transport chain and eventually donated to O2

gas.

Oxygen is required!

Glucose is completely oxidized.

C6H12O6 + 6O2 6CO2 + 6H2O + energy

Glucose Oxygen Carbon Water (heat or ATP)

Dioxide


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Mitochondria Inner Structure


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Organization of cristae


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Using Electrons to Make ATP

NADH & FADH2 contain

energized electrons.

NADH molecules carry their

electrons to the inner

mitochondrial membrane where

they transfer electrons to a

series of membrane bound

proteinsthe electron

transport chain.


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Producing ATP- Chemiosmosis

A strong gradient withmany protons outside thematrix and few inside is setup.

Protons are driven back

into the matrix.

They must pass throughspecial channels thatwill drive synthesis of

ATP. Oxidative

phosphorylation


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Energy Yield from Glucose

Metabolism Per glucose molecule, there is a net gain of

two ATP from glycolysis, which occurs in

the cytoplasm by substrate-levelphosphorylation.

The citric acid cycle, occurring in the matrix

of mitochondria, adds six more ATP, also bysubstrate-level phosphorylation.


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Most ATP is produced by the electron transport

system and chemiosmosis.

Per glucose molecule, ten NADH and two FADH2take electrons to the electron transport system;

three ATP are formed per NADH and two ATP per

FADH2

.

Electrons carried by NADH produced during

glycolysis are shuttled to the electron transport

chain by an organic molecule.

Energy Yield from Glucose

Metabolism


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Accounting of energy yield per glucose

molecule breakdown


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Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2 6CO2 + 2 ADP + 36 ATP + 6 H2O


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Metabolism of Proteins

Proteins digested in the gut into amino acidswhich are then absorbed into blood andextracellular fluid.

Excess proteins can serve as fuel likecarbohydrates and fats.

Nitrogen is removed producing carbon skeletonsand ammonia.

Carbon skeletons oxidized.


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Metabolism of Proteins

Ammonia is highly

toxic, but soluble.

Can be excreted by

aquatic organismsas ammonia.

Terrestrial organisms

must detoxify it first.


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Glycogensynthesis

Liver storage

Glucose toglycogen

Gluconeogenesis

Amino acidsGlycerol

Lactate

Synthetic (Anabolic) pathways

Figure 4-29: Gluconeogenesis


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Lipogenesis

Lipid synthesis


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Lipid Synthesis


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Alfonse, Biochemistry makes my head hurt!!


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1 Metabolism Metabolic Pathways 160712