chapt04 holes lecture animation[1]

Edited by Brenda HolmesMSN/Ed, RNAssociate Professor

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South Arkansas Community College

Chapter 4Cellular Metabolism

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• Metabolic processes – all chemical reactions that occur in the body

There are two (2) types of metabolic reactions:

• Anabolism• Larger molecules are made from smaller ones• Requires energy

• Catabolism• Larger molecules are broken down into smaller ones• Releases energy

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• Consists of two processes:• Anabolism• Catabolism

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• Anabolism provides the materials needed for cellular growth and repair

• Dehydration synthesis • Type of anabolic process• Used to make polysaccharides, triglycerides, and proteins• Produces water

CH2OH

H H

OH

O

H OH

Monosaccharide +

HHO

H

OH

H H

OH

O

H OH

Monosaccharide

HHO

H

OH

H H

OH

O

H OH

Disaccharide

H2O

Water+

HHO

H H H

OH

O

H OH

HO

H

OH

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CH2OH CH2OH CH2OH

Amino acid

N

H

H

C C

H

R

Dipeptide molecule ++

Peptide bond

Amino acid

N

H

H

C C

HH

H

RH

O

N

H

H

C C

H

RH

O

N

H

C C OH

R

H

OO

N

H

H

C C

H

R

N

H

C C OH

R

H

OO

Water

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O O

H2O

6

H C

H

Glycerol 3 fatty acid molecules+

OH HO

H C OH HO

H C

C

C

COH HO

H

O

O

C

C

C

O

O

O

H C

H

Fat molecule (triglyceride) +

H C

H C O

O

O

H

3 watermolecules

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

H2O

H2O

H2O

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O

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• Catabolism breaks down larger molecules into smaller ones

• Hydrolysis• A catabolic process• Used to decompose carbohydrates, lipids, and proteins• Water is used to split the substances• Reverse of dehydration synthesis

CH2OH

H H

OH

O

H OH

Monosaccharide +

HHO

H

OH

H H

OH

O

H OH

Monosaccharide

HHO

H

OH

H H

OH

O

H OH

Disaccharide

H2O

Water+

HHO

H H H

OH

O

H OH

HO

H

OH

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CH2OH CH2OH CH2OH

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Amino acid

N

H

H

C C

H

R

Dipeptide molecule ++

Peptide bond

Amino acid

N

H

H

C C

HH

H

RH

O

N

H

H

C C

H

RH

O

N

H

C C OH

R

H

OO

N

H

H

C C

H

R

N

H

C C OH

R

H

OO

Water

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O O

H2O

H C

H

Glycerol 3 fatty acid molecules+

OH HO

H C OH HO

H C

C

C

COH HO

H

O

O

C

C

C

O

O

O

H C

H

Fat molecule (triglyceride) +

H C

H C O

O

O

H

3 watermolecules

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

(CH2)14 CH3

H2O

H2O

H2O

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O

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• Enzymes• Control rates of metabolic reactions• Lower activation energy needed to start reactions• Most are globular proteins with specific shapes• Not consumed in chemical reactions• Substrate specific• Shape of active site determines substrate

Product molecule

Active site

(a) (b) (c)

Substrate molecules

Unalteredenzymemolecule

Enzyme-substratecomplex

Enzymemolecule

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• Metabolic pathways• Series of enzyme-controlled reactions leading to formation of a product• Each new substrate is the product of the previous reaction

• Enzyme names commonly:• Reflect the substrate• Have the suffix – ase• Examples: sucrase, lactase, protease, lipase

Substrate1

Enzyme A Substrate2

Enzyme B Substrate3

Enzyme C Substrate4

Enzyme DProduct

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• Cofactors • Make some enzymes active• Non-protein component• Ions or coenzymes

• Coenzymes• Organic molecules that act as cofactors• Vitamins

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• Factors that alter enzymes:• Heat• Radiation• Electricity• Chemicals• Changes in pH

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• Limited number of regulatory enzymes

• Negative feedback

Inhibition

Substrate1

Substrate2

Enzyme B Substrate3

Enzyme C Substrate4

Enzyme DProduct

Rate-limitingEnzyme A

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• Energy is the capacity to change something; it is the ability to do work • Common forms of energy:

• Heat• Light• Sound• Electrical energy• Mechanical energy• Chemical energy

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• Each ATP molecule has three parts:• An adenine molecule• A ribose molecule• Three phosphate molecules in a chain

• Third phosphate attached by high-energy bond

• When the bond is broken, energy is transferred • When the bond is broken, ATP becomes ADP

• ADP becomes ATP through phosphorylation

• Phosphorylation requires energy release from cellular respiration

Energy transferredand utilized bymetabolicreactions whenphosphate bondis broken

Energy transferredfrom cellularrespiration usedto reattachphosphate

PP P

P

P P P

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• Chemical bonds are broken to release energy

• We burn glucose in a process called oxidation

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• Occurs in a series of reactions:1. Glycolysis2. Citric acid cycle (aka TCA or Kreb’s Cycle)3. Electron transport system

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• Produces:• Carbon dioxide• Water• ATP (chemical energy)• Heat

• Includes:• Anaerobic reactions (without O2) - produce little ATP• Aerobic reactions (requires O2) - produce most ATP

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• Series of ten reactions• Breaks down glucose into 2 pyruvic acid molecules• Occurs in cytosol• Anaerobic phase of cellular respiration• Yields two ATP molecules per glucose molecule

Summarized by three main phases or events:1. Phosphorylation2. Splitting3. Production of NADH and ATP

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Event 1 - Phosphorylation• Two phosphates added to glucose• Requires ATP

Event 2 – Splitting (cleavage)• 6-carbon glucose split into two 3-carbon molecules

Phase 1priming

Phase 2cleavage

Phase 3oxidation andformation ofATP and releaseof high energyelectrons

2 ADP

2 NADH + H+

2 NAD+

2 NADH + H+

2 NAD+

P

ATP

PP

P

Glyceraldehydephosphate

Glucose

Dihydroxyacetonephosphate

2

4 ADP

ATP4

Fructose-1,6-diphosphate

O2

2 Pyruvic acid

2 Lactic acidTo citric acid cycleand electron transportchain (aerobic pathway)

Carbon atom

PhosphateP

P

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O2

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Event 3 – Production of NADH and ATP

• Hydrogen atoms are released• Hydrogen atoms bind to NAD+ to produce NADH• NADH delivers hydrogen atoms to electron transport system if oxygen is available• ADP is phosphorylated to become ATP• Two molecules of pyruvic acid are produced• Two molecules of ATP are generated

Phase 1priming

Phase 2cleavage

Phase 3oxidation andformation ofATP and releaseof high energyelectrons

2 ADP

2 NADH + H+

2 NAD+

2 NADH + H+

2 NAD+

P

ATP

PP

P

Glyceraldehydephosphate

Glucose

Dihydroxyacetonephosphate

2

4 ADP

ATP4

Fructose-1,6-diphosphate

O2

2 Pyruvic acid

2 Lactic acidTo citric acid cycleand electron transportchain (aerobic pathway)

Carbon atom

PhosphateP

P

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O2

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• If oxygen is not available:• Electron transport system cannot accept new electrons from NADH• Pyruvic acid is converted to lactic acid• Glycolysis is inhibited• ATP production is less than in aerobic reactions

Phase 1priming

Phase 2cleavage

Phase 3oxidation andformation ofATP and releaseof high energyelectrons

2 ADP

2 NADH + H+

2 NAD+

2 NADH + H+

2 NAD+

P

ATP

PP

P

Glyceraldehydephosphate

Glucose

Dihydroxyacetonephosphate

2

4 ADP

ATP4

Fructose-1,6-diphosphate

O2

2 Pyruvic acid

2 Lactic acidTo citric acid cycleand electron transportchain (aerobic pathway)

Carbon atom

PhosphateP

P

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O2

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• If oxygen is available: • Pyruvic acid is used to produce acetyl CoA• Citric acid cycle begins• Electron transport system functions• Carbon dioxide and water are formed• 34 molecules of ATP are produced per each glucose molecule

ATP2

ATP2

Glucose

Pyruvic acid Pyruvic acid

Acetyl CoA

CO2

2 CO2

Citric acid

O2

H2O

2e– + 2H+

Electron transport chain

ATP32-34

Cytosol

Mitochondrion

High energyelectrons (e–) andhydrogen ions (H+)

High energyelectrons (e–) andhydrogen ions (h+)

Oxaloaceticacid

High energyelectrons (e–) and hydrogen ions (H+)

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• Begins when acetyl CoA combines with oxaloacetic acid to produce citric acid• Citric acid is changed into oxaloacetic acid through a series of reactions• Cycle repeats as long as pyruvic acid and oxygen are available

• For each citric acid molecule: • One ATP is produced• Eight hydrogen atoms are transferred to NAD+ and FAD• Two CO2 produced

Citric acid cycle

ADP +ATP

Pyruvic acid from glycolysis

Citric acid

(start molecule)

Acetyl CoA

(replenish molecule)

Acetic acid

Oxaloacetic acid

(finish molecule)

Isocitric acid

CO2

CO2

CO2

Succinyl-CoASuccinic acidFAD

FADH2

Fumaric acid

Malic acid

Cytosol

Mitochondrion

NADH + H+

NAD+

NADH + H+

NAD+

NADH + H+

NAD+

CoA

CoA

CoA

CoA

P

NADH + H+

NAD+

P

CoA

Carbon atom

Phosphate

Coenzyme A

-Ketoglutaric acid

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ATPADP +ATP synthase

Electron transport chain

Energy

P

2H+ + 2e–

2e–

2H+

NADH + H+

NAD+

2H+ + 2e–

FADH2

FAD

O2

H2O

Energy

Energy

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• NADH and FADH2 carry electrons to the ETS• ETS is a series of electron carriers located in cristae of mitochondria• Energy from electrons transferred to ATP synthase• ATP synthase catalyzes the phosphorylation of ADP to ATP• Water is formed

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Glycolysis

Cyt

oso

lM

ito

cho

nd

rio

n

ATP2

Glucose

High-energy electrons (e–)

High-energy electrons (e–)

High-energy electrons (e–)

2e– and 2H+

ATP2

H2OO2

ATP32–34

CO2

Pyruvic acidPyruvic acid

2 CO2

Acetyl CoA

Citric acidOxaloacetic acid

1

3

4

2

Glycolysis

The 6-carbon sugar glucose is broken down in thecytosol into two 3-carbon pyruvic acid molecules witha net gain of 2 ATP and release of high-energyelectrons.

Citric Acid Cycle

The 3-carbon pyruvic acids generated by glycolysisenter the mitochondria. Each loses a carbon(generating CO2 and is combined with a coenzyme toform a 2-carbon acetyl coenzyme A (acetyl CoA). Morehigh-energy electrons are released.

Each acetyl CoA combines with a 4-carbon oxaloaceticacid to form the 6-carbon citric acid, for which the cycleis named. For each citric acid, a series of reactions removes 2 carbons (generating 2 CO2’s), synthesizes1 ATP, and releases more high-energy electrons.The figure shows 2 ATP, resulting directly from 2turns of the cycle per glucose molecule that entersglycolysis.

Electron Transport Chain

The high-energy electrons still contain most of thechemical energy of the original glucose molecule.Special carrier molecules bring the high-energyelectrons to a series of enzymes that convert much ofthe remaining energy to more ATP molecules. Theother products are heat and water. The function ofoxygen as the final electron acceptor in this last step iswhy the overall process is called aerobic respiration.

Electrontransport

chain

Citric acidcycle

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• Carbohydrate molecules from foods can enter:• Catabolic pathways for energy production• Anabolic pathways for storage

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• Excess glucose stored as: • Glycogen (primarily by liver and muscle cells)• Fat• Converted to amino acids

Hydrolysis

Monosaccharides

Energy + CO2 + H2O Glycogen or Fat Amino acids

Carbohydratesfrom foods

Catabolicpathways

Anabolicpathways

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High energyelectrons carried

by NADH and FADH2

Breakdown of simplemolecules to acetylcoenzyme Aaccompanied byproduction of limitedATP and high energyelectrons

H2O

2e– and 2H+

Waste products

–NH2

CO2

CO2

Citricacidcycle

Electrontransport

chain

Amino acids

Acetyl coenzyme A

Simple sugars(glucose)

Glycerol Fatty acids

Proteins(egg white)

Carbohydrates(toast, hashbrowns)

Food

Fats(butter)

Pyruvic acid

ATP

ATP

Breakdown of largemacromoleculesto simple molecules

Glycolysis

1

2

3

ATP

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© Royalty Free/CORBIS.

½ O2

High energyelectrons carried

by NADH and FADH2

Complete oxidationof acetyl coenzyme Ato H2O and CO2 produceshigh energy electrons(carried by NADH andFADH2), which yield muchATP via the electrontransport chain

Breakdown of simplemolecules to acetylcoenzyme Aaccompanied byproduction of limitedATP and high energyelectrons

H2O

2e– and 2H+

Waste products

–NH2

CO2

CO2

Citricacidcycle

Electrontransport

chain

Amino acids

Acetyl coenzyme A

Simple sugars(glucose)

Glycerol Fatty acids

Proteins(egg white)

Carbohydrates(toast, hashbrowns)

Food

Fats(butter)

Pyruvic acid

ATP

ATP

Breakdown of largemacromoleculesto simple molecules

Glycolysis

1

2

3

ATP

© Royalty Free/CORBIS.

½ O2

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• Instruction of cells to synthesize proteins comes from a nucleic acid, DNA

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• Gene – segment of DNA that codes for one protein

• Genetic information – instructs cells how to construct proteins; stored in DNA

• Genome – complete set of genes

• Genetic Code – method used to translate a sequence of nucleotides of DNA into a sequence of amino acids

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DNA Profiling Frees A Prisoner

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• Two polynucleotide chains• Hydrogen bonds hold nitrogenous bases together• Bases pair specifically (A-T and C-G)• Forms a helix• DNA wrapped about histones forms chromosomes

G C

G

G

A

T

C

C

A

P

G C P

TP

P

C G

P

GP

C P

AP P

P

Thymine (T)

Cytosine (C)

Adenine (A)

Guanine (G)

Nucleotide strand

Globularhistoneproteins

Metaphasechromosome

Segmentof DNAmolecule

Chromatin

(a) Hydrogen bonds

(b)

(c)

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• Hydrogen bonds break between bases• Double strands unwind and pull apart• New nucleotides pair with exposed bases• Controlled by DNA polymerase

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C

C

A T

C

C G

G

C

C

GCG

A

A

T

T

C G

C

A T

Newly formedDNA molecules

Region ofreplication

Original DNAmolecule

G

G

G

G

G

G

GG

G

C C

C

C

C G

A

A

AT

T

A

A

T

T

T

T

T A

A

A

T A

AT

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Nucleic Acid Amplification

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• Specification of the correct sequence of amino acids in a polypeptide chain• Each amino acid is represented by a triplet code

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• Transfer RNA (tRNA):• Carries amino acids to mRNA• Carries anticodon to mRNA• Translates a codon of mRNA into an amino acid

• Ribosomal RNA (rRNA):• Provides structure and enzyme activity for ribosomes

• Messenger RNA (mRNA):• Making of mRNA (copying of DNA) is transcription

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• Messenger RNA (mRNA):• Delivers genetic information from nucleus to the cytoplasm

• Single polynucleotide chain

• Formed beside a strand of DNA

• RNA nucleotides are complementary to DNA nucleotides (exception – no thymine in RNA; replaced with uracil)

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DNA RNA

SG

SC

S

S

S

S

C

G

T

A

S

S

S

S

G

C

A

U

Dire

ctio

n o

f “r

ead

ing

” co

de

P

P

P

P

P

P

P

P

P

P

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43

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MessengerRNA

1 DNAinformationis copied, ortranscribed,into mRNAfollowingcomplementarybase pairing

2 mRNA leavesthe nucleusand attachesto a ribosome

3 Translation begins as tRNA anticodonsrecognize complementary mRNA codons,thus bringing the correct amino acids intoposition on the growing polypeptide chain

4 As the ribosomemoves along themRNA, more aminoacids are added

5 At the end of the mRNA,the ribosome releasesthe new protein

6

Amino acidsattached to tRNA

Polypeptidechain

CytoplasmDNAdoublehelix

DNAstrandspulledapart

Transcription(in nucleus)

Translation(in cytoplasm)

Nucleus

C

Codon 1

Codon 2

Codon 3

Codon 4

Codon 5

Codon 6

Codon 7

GG

GG

G

AA

A

U

UC

CC

C

C

C

GGG

AMethionine

Glycine

Amino acidsrepresented

Serine

Alanine

Threonine

Alanine

Glycine

DNAstrand

MessengerRNA

AT

A

A

T

T

T

A TA T

A T

A T

A T

U A

U A

U A

G C

C

G CG C

G C

G CG C

G C

G

G

C

C

G C

C GU AC GC

G

G

GG

G

G

GG

G

G

C

CC

C

C

C

C

CC

C

A

A

A

A

A

T

T A

A T

A T

A T

A T

C G

G C

G C

G C

T A

T A

T A

C G

A TG C

T AC G

T AC G

C G

G C

A T

T AC G

G C

T

T

G

C G

C G

C G

C G

C GC G

C G

C G

Nuclearpore

tRNA moleculescan pick up anothermolecule of thesame amino acidand be reused

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G C

C G

A

G

G

C

U

C

T

C

C

G

A

G

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Next amino acid

Anticodon

Codons

Growingpolypeptidechain

1

1

2

2

3

3

4

4

5

5

6

6

7

CU G G

Ribosome

1

1

2

2

3

37

4

4

5

5

6 7

CCC G U

CU G C G U

Next amino acid

Anticodon

Codons

1

1

2

2

3

3

4

4

5

5

6

6

7

Peptide bond

CU G C G U

C CG C GU

6

MessengerRNA

TransferRNA

Nextamino acid

1

1

2

2

3

3

4

4

5

5

6 7

6 7

UCG GA AA A A AG G G G G G G GC C C C C C CU U

UCG GA AA A A AG G G G G G G GC C C C C C CU U

UCG GA AA A A AG G G G G G G GC C C C C C CU U

UCG GA AA A A AG G G G G G G GC C C C C C CU U

The transfer RNA moleculefor the last amino acid addedholds the growing polypeptidechain and is attached to itscomplementary codon on mRNA.

A second tRNA bindscomplementarily to thenext codon, and in doingso brings the next aminoacid into position on the ribosome.A peptide bond forms, linkingthe new amino acid to thegrowing polypeptide chain.

The tRNA molecule thatbrought the last amino acidto the ribosome is releasedto the cytoplasm, and will beused again. The ribosomemoves to a new position atthe next codon on mRNA.

A

A new tRNA complementary tothe next codon on mRNA bringsthe next amino acid to be addedto the growing polypeptide chain.

2

1

3

4

MessengerRNA

TransferRNA

Nextamino acid

TransferRNA

MessengerRNA

TransferRNA

Growingpolypeptidechain

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MicroRNAs and RNA Interference

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• Only about 1/10th of one percent of the human genome differs from person to person

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• Mutations – change in genetic information

• Result when:• Extra bases are added or deleted• Bases are changed

• May or may not change the protein

Code forglutamicacid

Mutation

Dir

ec

tio

n o

f “r

ea

din

g”

cod

e

Code forvaline

(a) (b)

S

S

S

C

T

A

P

P

P

S

S

S

C

T

T

P

P

P

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• Repair enzymes correct the mutations

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• Occurs from inheriting a mutation that then alters an enzyme• This creates a block in an otherwise normal biochemical pathway

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The Human Metabolome

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Important Points in Chapter 4:Outcomes to be Assessed

4.1: Introduction

Define metabolism.

Explain why protein synthesis is important.

4.2: Metabolic Processes

Compare and contrast anabolism and catabolism.

Define dehydration synthesis and hydrolysis.

4.3: Control of Metabolic Reactions

Describe how enzymes control metabolic reactions.

List the basic steps of an enzyme-catalyzed reaction.

Define active site.

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Important Points in Chapter 4:Outcomes to be Assessed

Define a rate-limiting enzyme and indicate why it is important in a metabolic pathway.

4.4: Energy for Metabolic Reactions

Explain how ATP stores chemical energy and makes it available to a cell.

State the importance of the oxidation of glucose.

4.5: Cellular Respiration

Describe how the reactions and pathways of glycolysis, the citric acid cycle, and the electron transport chain capture the energy in nutrient molecules.

Discuss how glucose is stored, rather than broken down.

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Important Points in Chapter 4:Outcomes to be Assessed

4.6: Nucleic Acids and Protein Synthesis

Define gene and genome.

Describe the structure of DNA, including the role of complementary base pairing.

Describe how DNA molecules replicate.

Define genetic code.

Compare DNA and RNA.

Explain how nucleic acid molecules (DNA and RNA) carry genetic information.

Define transcription and translation.

Describe the steps of protein synthesis.

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Important Points in Chapter 4:Outcomes to be Assessed

4.7: Changes in Genetic Information

Compare and contrast mutations and SNPs.

Explain how a mutation can cause a disease.

Explain two ways that mutations originate.

List three types of genetic changes.

Discuss two ways that DNA is protected against mutation.

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Quiz 4

Complete Quiz 4 now!

Read Chapter 5.