Chapter 4

Chapter 4, Metabolism

Section 1, Chapter 4

Cellular Metabolism

• Metabolism = Sum of all reactions in the body

Anabolism• Synthesizes smaller molecules into larger molecules• Provides materials for growth and repair• Consumes energy

Catabolism• Large molecules decompose into smaller molecules• Releases energy for cellular use

Metabolic reactions are of two types

ATP = energy

Dehydration Synthesis

• Type of anabolic reaction• Joins triglycerides, polysaccharides, and proteins• Water is formed from dehydration synthesis

Dehydration synthesis joining amino acids together

Dehydration Synthesis

• Synthesizes polysaccharides from monosaccharides

• Synthesizes proteins from amino acids

• Joins fatty acids to glycerol, forming form fats

• Synthesizes nucleic acids from nucleotides

Catabolism

• Reverse of Anabolism

• Breaks down molecules

• Releases energy from chemical bonds

• Example: Hydrolysis

Hydrolysis

• Type of Catabolic reaction• Reverse of dehydration synthesis• Requires water to break bonds

Hydrolysis

• Decomposes Polysaccharides into monosaccharides & disaccharides

• Decomposes proteins into amino acids

• Decomposes Fats into fatty acids & glycerol

• Decomposes Nucleic Acids into nucleotides

AnabolismCatabolism

Anabolism & Catabolism are reversible reactions

Enzymes control direction & rate of reactions

Enzyme Actions

Substrate

• Target molecule of an enzyme• Each enzyme acts on a specific substrate

Enzymes

• Are biological catalyst• They greatly reduce the activation energy required to start

a reaction.

Enzyme Characteristics

• Most all are Proteins

• Catalyze reactions - Increases the rate of reactions

• Reusable - Not consumed by reaction

• Specificity – Able to “recognize” a specific substrate

Enzyme Names

• Named for substrate they act upon

• Usually end with ____ ase.

• Examples:• Lipase: decomposes lipids• Protease: decomposes proteins• Nuclease: decomposes nucleic acids• ATP Synthase: synthesizes ATP molecules

a. Active site

• Region of enzyme that binds to substrate

b. Enzyme-Substrate Complex

• Enzyme temporarily binds to substrate

Enzyme releases product

• Enzyme is reused to join new substrates

Rates of reactions are limited by:

• The concentration of substrate

• The concentration of enzyme

• The efficiency of enzymes• Some enzymes handle 2-3 molecules per second• Other enzymes handle thousands per second

Metabolic Pathways• Complex series of reactions leading to a product

• Pathways are controlled by several enzymes

Example: Catabolic pathway for the breakdown of glucose

• The product of each reaction becomes the substrate of next reaction.

• Each step requires its own enzyme

• “Rate-Limiting Enzyme” • Least efficient enzyme in group • Rate-limiting enzyme is usually first in sequence

Metabolic Pathways

• Enzyme A = Rate-limiting Enzyme

Negative Feedback in Metabolic Pathway

• Product of reaction often inhibits the rate-limiting enzyme.

• Negative feedback prevents the overproduction of a product.

Cofactor

• Combines with and activates some enzymes• Exposes the active site of enzyme to substrate

• Cofactors are non-proteins

• Include ions (zinc, iron, copper) and coenzymes

Coenzymes = organic cofactors

• Coenzymes include Vitamins (Vitamin A, B, D)• Reusable – required in small amounts

Vitamins• Essential organic molecules that humans cannot

synthesize - must come from diet

• Many vitamins are coenzymes

• Vitamins can function repeatedly, so can be used in small amounts.

• Example: Coenzyme A

Energy for Metabolic Reactions

Energy: is the capacity to change something, or ability to do work.

Common forms of energy: HeatLightSoundChemical energyMechanical energyElectrical energy

Energy cannot be created or destroyed. Only transferred from one form to another

Fuel (chemical energy) +

Oxygen

= Kinetic Energy + CO2 + H2O

Think of a combustion engine

Cellular Respiration

• Cell Respiration: is the transfer of energy from food to make available for cellular use

• Energy is stored in the electrons of food molecules

• Oxidation: “controlled burning” of food molecules to release their energy

• Cellular respiration requires enzymes


Glucose (C6H12O6) + 6O2 → Energy for ATP + H2O + CO2

ATP

Energy from foods such as glucose is used to make ATP

End of Section 1, Chapter 4

Chapter 4, Metabolism…continued


Mitochondria

Mitochondria


Glucose (C6H12O6) + 6O2 → Energy for ATP + H2O + CO2

ATP

Energy from Chemical bonds

Energy forATP synthesis

Adenosine Triphosphate (ATP)Currency of Energy for cells

AdenosineTriphosphate

Adenosine Diphosphate (ADP)

AdenosineDiphosphate

ADP +

Phosphate+

Energy

ATP

hydrolysis

ADP

Energy released by hydrolyzing 3 rd phosphate group

Products:

Cell respiration regenerates ATP

Phosphorylation of ADP resynthesizes ATP

ATP provides energyFor metabolic reactions

Cell RespirationRegenerates ATP

Figure 4.8

Cell Respiration

Anaerobic• No oxygen required• Yields little energy• Yields 2 ATP per glucose

Aerobic• Requires oxygen• Much greater energy yield• Up to 38 ATP per glucose

glycolysis

Acetyl CoA synthesis

Citric Acid Cycle

Electron Transport Chain

4 Reactions of Cell Respiration

Glycolysis

• Series of 10 reactions

• Breaks down glucose into 2 Pyruvic Acid molecules

• Occurs in Cytoplasm of Cell

• Anaerobic Reaction (no oxygen required)

• Yields • 2 ATP (net gain) per glucose• 2 NADH molecule• 2 Pyruvic Acid molecules

• 2 Phosphates are added to end of glucose • Glucose is a 6-carbon sugar

• Primes glucose for further reactions

• Consumes 2 ATP

GlycolysisStep 1. Phosphorylation of glucose

GlycolysisStep 2. Lyse glucose

Glucose (6 carbon)

Pyruvic Acid(3 Carbon)


2 NADH4 ATP

• 6-Carbon glucose is split into 2 3-carbon Pyruvic Acid molecules• Produces 4 ATP total • Produces 2 NADH molecules

Glycolysis

+ 2 ATP net gain

- 2ATP consumed

+4 ATP produced

Products of Glycolysis• 2 ATP• 2 Pyruvic Acids• 2 NADH (electron carriers)

PRODUCTION OF NADH & FADH2

1. NAD+ + 2H

• NADH

1• F

ADH

2

2

• NADH & FADH2 carry electrons from food to electron transport chain• The transport of electrons provides energy for ATP synthesis

2 electrons attached to hydrogen

NADH + H+HH+

2. FAD + FADH22H

NADH & FADH2 carry electrons to the electron transport chain

2 electrons attached to NADH

2 electrons attached to FADH2

Products of Glycolysis• 2 ATP• 2 NADH (electron carriers)• 2 Pyruvic Acids

Pyruvic Acid(3 Carbon)If Oxygen is

available

If no Oxygen is available

(anaerobic)

Aerobic Pathway

AnaerobicPathway

Fate of pyruvic acid depends on oxygen availability

Oxygen required to accept electrons from

NADH & FADH2

No oxygen to receive electrons from NADH

AnaerobicPathway

NAD

2 electrons

Pyruvic Acid + Lactic Acid + NAD+H

Without Oxygen, NADH donates its electrons to pyruvic acid

Lactic Acid is formed as waste

This regenerates NAD+, which is used again for glycolysis

AnaerobicPathway

Anaerobic Respiration• Inefficient reaction; yields only 2 ATP • Consumes a great deal of glucose• Quick source of energy; for intense exercise


Once oxygen is available:Lactic Acid is converted back to glucose by the liver

Aerobic Respiration


mitochondria

If Oxygen is available, pyruvic acid can continue through aerobic respiration inside the mitochondria


Aerobic Pathways Include:1. Acetyl CoA synthesis2. Citric Acid Cycle3. Electron Transport Chain (ETC)

Mitochondria

Mitochondria• Powerhouse of cell• Synthesizes ATP• 2 layers

– Outer Membrane– Inner Membrane

• Cristae • highly folded inner membrane• Greatly increases surface area for reactions

Synthesis of Acetyl CoA

Pyruvic Acid is converted into Acetyl CoA

Acetyl CoA = substrate for Citric Acid Cycle

Synthesis of Acetyl CoAPyruvic Acid(3 Carbon)

Acetic Acid(2 Carbon)

CO2

(waste)

CoA

Acetyl CoA

(Enters Citric Acid Cycle)

(coenzyme A)

1 carbon is lost as CO2

Products from Acetyl CoA Synthesis

• 1 molecule of CO2

• Acetyl CoA

Citric Acid Cycle

Acetyl CoA + Oxaloacetic Acid → Citric Acid(2 carbons) (4 carbons) (6 carbons)

Citric Acid is converted back to Oxaloacetic acid through a series of 8-9reactions

Citric Acid = Start molecule of cycle

Oxaloacetic acid = end molecule of cycle

Begins when Acetyl CoA combines with Oxaloacetic Acid to form Citric Acid.

Acetyl CoA(2 carbons)

Oxaloacetic Acid(4 carbons)

+

Citric Acid(6 Carbons)

Oxaloacetic acidis regenerated

2CO2

(waste) Citric Acid Cycle

8-9 reactions

FAD

FADH2

3NAD+3 NADH

2 ATP

2ADP

• 2 ATP• 3 NADH = transports electrons to ETC• 1 FADH2 = transports electrons to ETC

• 2 CO2

Products of Citric Acid Cycle

Electron transport chain (ETC)

• Occurs on inner membrane of mitochondria• ATP synthase (enzyme): phosphorylates ADP → ATP• Involves a chain of 3 enzymes (protein complexes)• Produces 32-34 ATP per glucose• Requires Oxygen to accept electrons

Enzyme Complexes in ETC• Transport Complex Proteins

– 3 Membrane proteins on inner membrane of Mitochondria

– NADH & FADH2 transfer electrons to complex proteins

– Electrons are passed from one complex to the next complex

– Transfer of electrons releases energy to power ATP Synthase

• ATP Synthase– Phosphorylates ADP into ATP– Powered by Transport Complex Proteins

½ O2(final electron acceptor)

NADH

2 electrons

Complex I

Complex II

Complex III

ATP SynthaseADP + PATP

NAD+(reused)

2H+

energy

energy

energy

+ H2O

ETC

Without Oxygen to accept electrons, ETC would grind to a halt!

Decreasing energy

Products of Electron Transport Chain• H2O

• 32-34 ATP

Lipids & Proteins can also be broken down

for ATP synthesis

Most common entry point to aerobic respiration is into citric

acid cycle as acetyl coA

Summary of catabolismof proteins, fats, & carbohydrates


DNA Replication & Protein Synthesis


DNA RNAtranscription

Proteinstranslation

Pathway of Protein Synthesis

DNA Replication (DNA Synthesis)

DNA DNACopy of original

replication

Definitions

Gene = portion of DNA that encodes for one protein

Genetic code = 3 letter DNA sequence that encodes for 1 amino acid

Genome = complete set of genetic instructions for an organism

Human genome = 46 chromosomes in diploid pairs

Properties of DNA 1. double-stranded nucleic acid2. sugar phosphate backbone3. sugar = deoxyribose4. contains nitrogenous bases (B)5. stabilized by hydrogen bonds6. antiparallel strands (opposite directions)

Strand 2Strand 1

Antiparallel Hydrogen bonds

backbonebackbone

Adenine & Guanine = Purines • 2 organic rings

Thymine & Cytosine = Pyrimidines• 1 organic ring

4 nitrogenous basesAdenine (A) Thymine (T)Cytosine (C) Guanine (G)

Properties of DNA

Complementary Base Pairs

Purine pairs with Pyrimidine:

Adenine pairs with ThymineGuanine pairs with Cytosine

A & T = complimentary base pairG & C = complementary base pair

C A C C T G GOriginal DNA strand:

Complimentary strand: G T G G A C C

H-bonds stabilizecomplimentary

base pairs

DNA is twisted into adouble helix

Overview of DNA Replication

• Occurs during S-phase

• Original DNA strand is used as a template to synthesize a new complimentary DNA strand.

• Catalyzed by DNA Polymerase – Synthesizes new DNA strand

• Semi-Conservative – One strand of the replicated DNA is new, the other is the original molecule.

DNA Replication

A C T A A T A A C G G A T

A T T G C C T AT G A T T

Hydrogen Bonds

C T A G

G A T C

Original DNA strand

sugar phosphate backbone

Strand 1

Strand 2

DNA Replication

A C T A A

T A A C G G A T

A T T G C C T A

T G A T T C T A G

G A T C

Step 1. Hydrogen bonds break, and strands separate

Replication bubble

DNA Polymerase

DNA Polymerase

Step 2. DNA Polymerases attach to open strands

H bonds continue to break

DNA Replication

A C T A A

T A A C G G A T

A T T G C C T A

T G A T T C T A G

G A T C

Step 3. DNA Polymerase adds new bases

Replication bubble

A T T G C C

A TAGGC

T A

AT

DNA Replication

A C T A A T A A C G G A T

A T T G C C T AT G A T T C T A G

G A T C

Step 3. DNA Polymerase adds new bases

A T T G C C

A TAGGC

T A

AT

C T A G

AATCA T T T

TTAGT

C

DNA Replication

A C T A A T A A C G G A T G A T C

A T T G C C T A C T A GTTAGT

A T T G C C T AT G A T T C T A G

A TAGGCATAATCA T T T C

2 Complete DNA moleculesEach with 1 original strand & 1 new strand

The two DNA molecules separate during mitosis



Transcription & Translation

Transcription

RNA synthesis from DNA template

RNA molecule

1. single-stranded nucleic acid

2. sugar phosphate backbone

3. sugar = ribose

4. Uracil (U) replaces Thymine (T)U & A = complimentary base pair

Properties of RNA

76

3 RNA Molecules

• Transfer RNA (tRNA):• Translates a codon of MRNA into an amino acid • Carries amino acids to mRNA• Anticodons on tRNA are complimentary to codons of mRNA•

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

• Messenger RNA (mRNA):• Transcribed from DNA in nucleus

mRNA Molecules

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

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

DNA mRNA

Transcription

1. Synthesis of messenger RNA (mRNA) from DNA template

2. Occurs in nucleus

3. Only 1 of the DNA strands is transcribed

4. Transcription is catalyzed by RNA Polymerase

A C T A C T A A C G G A T

A T T G C C T AT G A T G C T A G

G A T C

Step 1. RNA Polymerase attaches to DNA strands& breaks Hydrogen bonds

Strand 1

Strand 2

RNAPolymerase

DNA strands

Transcription

A C T A A

T A C C G G A T

A T G G C C T A

T G A T T

C T A G

G A T C

Step 2. Strands Separate

Replication bubble

Step 3. RNA Polymerase synthesizes mRNAusing DNA strand as a template

A UG G C CU A C U A GRNAPolymerase

mRNA

Transcription

A C T A A

T G A T T

Step 4. RNA Polymerase releases mRNA & DNA resumes original structure

T A C C G G A T G A T C

A T G G C C T A C T A G

A UG G C CU A C U A G

mRNA

RNAPolymerase

Transcription

A C T A A

T G A T T

Step 5. mRNA is undergoes further processing & leaves nucleus

T A C C G G A T G A T C

A T G G C C T A C T A G


mRNA

Transcription

DNA strands


Properties of mRNA

• Codon = 3 letter sequence that encodes for an amino acid • All mRNA begin with AUG “Start Codon”

Start Codon

mRNA

Examples of CodonsNote: • Codons are redundant - Each amino acid corresponds to more than one codon

• e.g. UCU, UCC, and UCA all encode for Serine

•Start Codon (AUG) initiates translation

•Stop Codons terminate translation

The codon sequence of mRNAdetermines the amino acid sequenceof a protein.

Figure 4.23

Protein Synthesis

Translation =

Synthesis of proteins, using mRNA as template

1. Occurs on Ribosomes in cytoplasm

2. transfer RNA (tRNA) transports amino acids to mRNA

3. anticodons on tRNA align with codons on mRNA

tRNA

1. Anticodon

2. Amino acid binding site

Clover-leaf shape RNA with 2 important regions

Ribosomes

• Small particle of protein & ribosomal RNA (rRNA)

• Ribosomes have 2 subunits• Small subunit binds to mRNA• Large subunit holds tRNA & amino acids

• Small subunit has 2 binding sites for adjacent mRNA codons

• Ribosomes link amino acids by peptide bonds

large subunit

small subunit

Binding sites with codons

anticodons

Peptide bond forming

Ribosomes

1. mRNA binds to the small subunit of a Ribosome.

2. The ribosome ‘reads’ the mRNA sequence

3. tRNA brings amino acids to the ribosomes, aligning their anticodons with mRNA codons

4. The Ribosome links the amino acids together

5. Polypeptide chain lengthens

Sequence of Translation

Translation- Figure 4.24Anchors polypeptide.

Translation

tRNA released

TRANSCRIPTION

TRANSLATIONFigure 4.23

After translation Chaperone proteins fold protein into its configuration

Enzymes may further modify proteins after translation = post-translational modification• Phosphorylation – adding a phosphate to the protein• Glycosylation – adding a sugar to the protein


Education

Chapter 4