Chapter 4

Chapter 4

Energy and Cellular Metabolism

About this Chapter

• Energy in biological systems• Chemical reactions• Enzymes• Metabolism• ATP production• Synthetic pathways

Figure 4-1

Energy: Biological Systems

• Energy transfer in the environment

Photosynthesistakes place in

plant cells, yielding:

Radiantenergy

Energy lostto environment

Heatenergy

Energy stored inbiomolecules

Sun

Respirationtakes place in

human cells, yielding:

Energy for work

Energy storedin biomolecules

H2O

+

+

Transfer of radiantor heat energy

Transfer of energyin chemical bonds

KEY

CO2

CO2

CO2 +

H2ON2

Energy: Capacity to Do Work

• Chemical work• Making and breaking of chemical bonds

• Transport work• Moving ions, molecules, and larger particles• Can create concentration gradients

• Mechanical work• Used for movement

Kinetic and Potential Energy

Figure 4-2

Thermodynamic Energy

• First law of Thermodynamics• Total amount of energy in the universe is

constant• Second law of Thermodynamics• Processes move from state of order to disorder

Figure 4-3

Chemical Reactions: Overview

• Activation energy is the energy that must be put into reactants before a reaction can proceed

• A + B C + D

Chemical Reactions: Exergonic and endergonic

Figure 4-4

KEY

Activation energy

Activation energy

Net freeenergychange

C+D

A+B G+H


E+F

Reactants

Activation of reaction

Reaction process

Products

(a) Exergonic reactions (b) Endergonic reactions

Chemical Reactions: Coupling

Figure 4-5

Enzymes: Overview

• Isozymes • Catalyze same reaction, but under different

conditions• May be activated, inactivated, or modulated• Coenzymes vitamins• Chemical modulators temperature and pH

Enzymes: Lower activation energy

Figure 4-6

KEY


Activation energy

C+D

ReactantsActivation of reactionReaction processProducts

A+B

Enzymes: Law of Mass Action

Figure 4-9a

Enzymes: Law of Mass Action

Figure 4-9b

Enzymes: Types of Reactions

Table 4-4

Figure 4-10

Metabolism: Overview

• A group of metabolic pathways resembles a road map

Metabolism: Cell Regulation

1. Controlling enzyme concentrations2. Producing allosteric and covalent modulators3. Using different enzymes for reversible

reactions4. Isolating enzymes within organelles5. Maintaining optimum ratio of ATP to ADP


Figure 4-11

Feedback inhibition

enzyme 3enzyme 2enzyme 1


Figure 4-12

H2OCO2 PO4 PO4

(a)

Carbonic acid Glucose 6-phosphate

Glucose + +Glucose

Glucose 6-phosphate

(c)(b)

carbonicanhydrase

carbonicanhydrase

glucose 6-phosphatase

hexokinasehexokinase

+

Figure 4-13

ATP Production: Overview

• Overview of aerobic pathways for ATP production

Glycerol

Fatty acids

Aminoacids

Aminoacids

Aminoacids

CO2

ADP

Cytosol

Mitochondrion

ATP

ADP

GLYCOLYSIS

Pyruvate

Acetyl CoA

Glucose

H2OO2

High-energy electronsand H+

ELECTRON TRANSPORT SYSTEMATP

ADP

CITRICACID

CYCLEATP

High-energyelectrons

Acetyl CoA

Citric acidcycle

Figure 4-14

ATP Production: Glycolysis

Glucose + 2 NAD+ + 2 ADP + P

2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H20

Glucose 6-phosphate

Fructose 6-phosphate

Fructose 1,6-bisphosphate

Dihydroxyacetonephosphate

ATP

ADP

ATP

ADP

This sectionhappens twicefor each glucosemolecule that begins glycolysis

= Carbon= Oxygen= Phosphate group

(side groups not shown)

Glyceraldehyde 3-phosphate

1, 3-Bisphosphoglycerate

3-Phosphoglycerate

2-Phosphoglycerate

Phosphoenol pyruvate

Pyruvate

ADP

Glucose

H2O

NADH

KEY

ATP

ATP

NAD+

ADP

Figure 4-15

ATP Production: Pyruvate Metabolism

• Pyruvate can be converted into lactate or acetyl CoA

PyruvateAcetyl CoA

H and –OH not shown

= Carbon= Oxygen

= Coenzyme A

KEY

Acetyl CoA

Acyl unit

CoA

CoA

Cytosol

Mitochondrialmatrix

Pyruvate

Pyruvate

Lactate

NAD+

CO2

NADH

NADH

NAD+Anaerobic Aerobic

CITRIC ACIDCYCLE

CoA

Figure 4-16

ATP Production: Citric Acid Cycle

• Acetyl CoA enters the citric acid cycle producing3 NADH, 1 FADH2, and 1 ATP

KEY

High-energyelectrons

Acetyl CoA

Citric acidcycle

Fumarate (4C)

Malate (4C)

Oxaloacetate (4C)

H2O

Side groups not shown

FADH2

NADH

NAD+

Acetyl CoACoA

CoA

CoA

= Carbon= Oxygen= Coenzyme A

Citrate (6C)

a Ketoglutarate (5C)

Succinyl CoA (4C)Succinate (4C)

ATP

CO2

CO2

NADH

NADHFAD

NAD+

ADP

CITRIC ACID CYCLE

CoA

GDP + PiGTP

CoA

NAD+

Isocitrate (6C)

CoA

ATP Production: Electron Transport

Figure 4-17

H+

H+

H+H+

Mitochondrialmatrix

Matrix pool of H+

4e–

e–

Innermitochondrial

membrane

ADP+ Pi

CITRICACID

CYCLE

High-energy electrons

O2 +2 H2O

ATP

H+H+

Cytosol

Outermitochondrial

membrane

High-energy electronsfrom glycolysis

H+

Intermembranespace

Energy released during metabolism is captured by high-energy electrons carried by NADH andFADH2.

Energy from high-energy electrons moving along the electron transport system pumps H+ from the matrix into the intermembrane space.

Electrons at the end of theelectron transport system are back to their normal energy state. They combine with H+ and oxygen to form water.

Potential energy captured inthe H+ concentration gradient is converted to kinetic energy when H+ ions pass through theATP synthase. Some of the kinetic energy is captured as ATP.

1

1 2 3 4

2

3

4ATP

synthase

ELECTRON TRANSPORT SYSTEM


Figure 4-17, step 1

Mitochondrialmatrix

e–

Innermitochondrial

membrane

CITRICACID

CYCLE


Cytosol

Outermitochondrial

membrane


Intermembranespace


1

1



Figure 4-17, steps 1–2

H+

H+H+

Mitochondrialmatrix

e–

e–

Innermitochondrial

membrane

CITRICACID

CYCLE


H+H+

Cytosol

Outermitochondrial

membrane


H+

Intermembranespace



1

1 2

2




H+

H+H+

Mitochondrialmatrix

Matrix pool of H+

4e–

e–

Innermitochondrial

membrane

CITRICACID

CYCLE


O2 +2 H2O

H+H+

Cytosol

Outermitochondrial

membrane


H+

Intermembranespace




1

1 2 3

2

3


H+

H+

H+H+

Mitochondrialmatrix

Matrix pool of H+

4e–

e–

Innermitochondrial

membrane

ADP+ Pi

CITRICACID

CYCLE


O2+2 H2O

ATP

H+H+

Cytosol

Outermitochondrial

membrane


H+

Intermembranespace




Potential energy captured inthe H+ concentration gradient is converted to kinetic energy when H+ ions pass through theATP synthase. Some of the kinetic energy is captured as ATP.

1

1 2 3 4

2

3

4ATP

synthase




NADH and FADH2 ATP by oxidative phosphorylation

ATP Production: Energy Yield

Figure 4-18

2 Acetyl CoA

Citric acidcycle

NADH ATP CO2FADH2

2*+4

–2

2 2

NADH ATP CO2FADH2

2 4

–2

–2

6 2 2

26-28

30-32ATP

6H2O

6CO2

2ATP

0NADH4

AEROBIC METABOLISM C6H12O6 + 6 O2 6 CO2 + 6 H2O ANAEROBIC METABOLISM C6H12O6 2 C3H6O3 (Lactic acid)

* Cytoplasmic NADH sometimes yield only 1.5 ATP/NADH instead of 2.5 ATP/NADH.

TOTALS

TOTALS

GLYCOLYSIS

ELECTRON TRANSPORTSYSTEM

2 Pyruvate

1 Glucose

High-energy electronsand H+

6 O2

2 Pyruvate

2 Lactic acid

1 GlucoseGLYCOLYSIS

ATP Production: Large Biomolecules

• Glycogenolysis• Glycogen• Storage form of glucose in liver and skeletal

muscle• Converted to glucose or glucose 6-phosphate

Figure 4-20

ATP Production: Protein Catabolism and Deamination

(a) Protein catabolism

NADH + H+NAD + H2O

H2OHydrolysis ofpeptide bond

Peptide

Protein or Peptide

Amino acid

Deamination

NH3

Organic acid

Ammonia

Amino acid

(b) Deamination

Glycolysis orcitric acid cycle

NH4+

H+

UreaAmmonia Ammonium

(c)+

+

NH3

ATP Production: Lipolysis

Figure 4-21

Triglyceride

Fatty acid

Cytosol

Lipases digest triglyceridesinto glycerol and 3 fatty acids.

Glycerol becomes aglycolysis substrate.

b-oxidation chops 2-carbonacyl units off the fatty acids.

Glucose

Glycerol

GLYCOLYSIS

Pyruvate

Mitochondrialmatrix

CoA

CoAAcetyl CoA

CO2

CITRICACID

CYCLE

Acyl units become acetylCoA and can be used in the citric acid cycle.

Acyl unit

b-oxidation

11

22

3

3

44

Synthesis: Gluconeogenesis

Figure 4-22

Pyruvate

Glucose

Liver, kidney

GLYCEROL

AMINO ACIDS

AMINO ACIDS

Glucose 6-phosphate

GLUCONEOGENESIS

Glucosesynthesis

LACTATE

Synthesis: Lipids

Figure 4-23

CoA

Fatty acidsynthetase

Glycerol

Fatty acids

Triglyceride

GLYCOLYSIS

Glucose

Acylunit

Glycerol can be made from glucose through glycolysis.

Two-carbon acyl units from acetyl CoAare linked together by fatty acid synthetase to form fatty acids.

One glycerol plus 3 fatty acidsmake a triglyceride.

Pyruvate

Acetyl CoA

1

2

3

1 32

Synthesis: Lipids

Figure 4-23, steps 1

CoA

Glycerol

GLYCOLYSIS

Glucose

Acylunit


Pyruvate

Acetyl CoA

1

1

Synthesis: Lipids



Glycerol

Fatty acidsAcylunit

Two-carbon acyl units from acetyl CoAare linked together by fatty acid synthetase to form fatty acids.

2

2

CoA

GLYCOLYSIS

Glucose

Acylunit


Pyruvate

Acetyl CoA

1

1

Synthesis: Lipids


CoA


Glycerol

Fatty acids

Triglyceride

GLYCOLYSIS

Glucose

Acylunit


One glycerol plus 3 fatty acidsmake a triglyceride.

Pyruvate

Acetyl CoA

1

2

3

1 32 Two-carbon acyl units from acetyl CoAare linked together by fatty acid synthetase to form fatty acids.

Synthesis: DNA to Protein

Figure 4-25

1 GENE ACTIVATION

TRANSCRIPTION

mRNA PROCESSING

TRANSLATION

POST-TRANSLATIONALMODIFICATION

Gene Regulatory proteins

Constitutivelyactive

Induction

Alternativesplicing

ProcessedmRNA

Interference

mRNA

Protein chain

Repression

Regulatedactivity

siRNA

mRNA “silenced”

• rRNA in ribosomes• tRNA• Amino acids

Folding andcross-links

Assembly intopolymeric proteins

Addition of groups: • sugars • lipids • -CH3 • phosphate

Cleavage intosmaller peptides

Cytoplasm

Nucleus

2

3

4

5



1 GENE ACTIVATION



Induction Repression

Regulatedactivity

Cytoplasm

Nucleus



1 GENE ACTIVATION

TRANSCRIPTION



Induction

mRNA

Repression

Regulatedactivity

Cytoplasm

Nucleus

2



1 GENE ACTIVATION

TRANSCRIPTION

mRNA PROCESSING



Induction

Alternativesplicing

ProcessedmRNA

Interference

mRNA

Repression

Regulatedactivity

siRNA

mRNA “silenced”

Cytoplasm

Nucleus

2

3



1 GENE ACTIVATION

TRANSCRIPTION

mRNA PROCESSING

TRANSLATION



Induction

Alternativesplicing

ProcessedmRNA

Interference

mRNA

Protein chain

Repression

Regulatedactivity

siRNA

mRNA “silenced”


Cytoplasm

Nucleus

2

3

4



1 GENE ACTIVATION

TRANSCRIPTION

mRNA PROCESSING

TRANSLATION

POST-TRANSLATIONALMODIFICATION



Induction

Alternativesplicing

ProcessedmRNA

Interference

mRNA

Protein chain

Repression

Regulatedactivity

siRNA

mRNA “silenced”


Folding andcross-links

Assembly intopolymeric proteins

Addition of groups: • sugars • lipids • -CH3

• phosphate

Cleavage intosmaller peptides

Cytoplasm

Nucleus

2

3

4

5

Protein: Transcription

Figure 4-26

RNA polymerase binds to DNA.

The section of DNA that containsthe gene unwinds.

RNA bases bind to DNA,creating a single strand of mRNA.

mRNA and the RNA polymerasedetach from DNA, and the mRNAgoes to the cytoplasm.

RNApolymerase

RNApolymerasemRNA strand released

mRNAtranscript

RNApolymerase

DNA

Sensestrand

Antisensestrand

Site ofnucleotide assembly

Leaves nucleusafter processing

LengtheningmRNA strand

RNA bases

1

2

3

4

Protein: Transcription

Figure 4-27

Introns removedIntrons removed

Transcribed sectionPromoter

DNA

UnprocessedmRNA

Exons for protein #1 Exons for protein #2

Gene

Antisense strand

Sensestrand

TRANSCRIPTION

Protein: Transcription and Translation

Figure 4-28

1

Translation

Termination

Outgoing “empty” tRNA

tRNA

mRNA

Amino acid

Ribosomalsubunits

Completedpeptide

Growingpeptidechain

mRNA Ribosome

Incoming tRNAbound to anamino acid

Anticodon

Transcription

mRNA processing

Attachment of ribosomal subunits

RNApolymerase

DNA

Nuclearmembrane

2

3

4

5



1

RNApolymerase

DNA

Nuclearmembrane

Transcription



1

RNApolymerase

DNA

Nuclearmembrane

2

Transcription

mRNA processing



1

RNApolymerase

DNA

Nuclearmembrane

2

3

Transcription

mRNA processing




1


tRNA

Amino acid

Growingpeptidechain

mRNA Ribosome


Anticodon

RNApolymerase

DNA

Nuclearmembrane

2

3

4 Translation

Transcription

mRNA processing




1

Translation

Termination


tRNA

mRNA

Amino acid

Ribosomalsubunits

Completedpeptide

Growingpeptidechain

mRNA Ribosome


Anticodon

Transcription

mRNA processing


RNApolymerase

DNA

Nuclearmembrane

2

3

4

5

Protein: Post-Translational Modification

• Protein folding• Cross-linkage• Cleavage• Addition of other molecules or groups• Assembly into polymeric proteins

Figure 4-29

Protein: Post-Translational Modification and the Secretory Pathway

mRNA is transcribed from thegenes in the DNA.

mRNA leaves the nucleusand attaches to cytosolicribosomes, initiating translation and protein synthesis.

Some proteins are released byfree ribosomes into the cytosolor are targeted to specific organelles.

Ribosomes attached to therough endoplasmic reticulumdirect proteins destined forpackaging into the lumen of the RER.

Proteins are modified as theypass through the lumen ofthe ER.

Transport vesicles move theproteins from the ER to theGolgi complex.

Gogli cisternae migrate fromthe cis-face toward the cellmembrane.

Some vesicles bud off thecisterna and move in aretrograde fashion.

At the trans-face, some vesicles bud off to form lysosomes.

Other vesicles becomesecretory vesicles that releasetheir contents outside the cell.

Cytosolicprotein

Endoplasmicreticulum

Transport vesicle

RetrogradeGolgi-ERtransport

Cis-Golgi complex

Lysosome orstorage vesicle Trans-Golgi

complex

Secretoryvesicle

Cellmembrane Extracellular space

Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

6

4

2

7

8

10

9

5

6

7

8

10

9


Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore



1

1





Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

2






Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

2







Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

4

2








Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

4

2

5









Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

6

4

2

5

6










Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

6

4

2

7

5

6

7











Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

6

4

2

7

8

5

6

7

8












Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

6

4

2

7

8

9

5

6

7

8

9












Other vesicles becomesecretory vesicles that releasetheir contents outside the cell.

Cytosolicprotein


Transport vesicle


Cis-Golgi complex


complex

Secretoryvesicle


Cytosol

Cisterna

Nucleus

mRNA

DNA

Ribosome

Growingamino-acid

chain

Targetedproteins

Peroxisome

Mitochondrion

Nuclearpore

1

1

2

3

3

4

5

6

4

2

7

8

10

9

5

6

7

8

10

9

Summary

• Energy• Chemical• Transport• Mechanical

• Kinetic energy• Potential energy

Summary

• Chemical reactions• Reactants• Products• Reaction rate

• Free energy and activation energy • Exergonic versus endergonic reactions• Reversible versus irreversible reactions

Summary

• Enzymes• Definition • Characteristics• Law of mass action• Type of reactions

Summary

• Metabolism• Catabolic versus anabolic reactions• Control of metabolic pathways• Aerobic versus anaerobic pathways

Summary

• ATP production• Glycolysis• Pyruvate metabolism• Citric acid cycle• Electron transport chain

• Glycogen, protein, and lipid metabolism

Summary

• Synthetic pathways• Gluconeogenesis • Lipid synthesis• Protein synthesis• Transcription• Translation• Post-translational modification

Documents

Chapter 4