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Chapter 04

Lecture Outline
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4.1 Metabolic Reactions

• Metabolism: Sum of all chemical reactions in the body

--
-
- -

• Cellular Metabolism: Sum of all chemical reactions

- -
occurring in a cell; metabolic reactions usually occur in
-

pathways or cycles.
There are 2 types of metabolic reactions:

=
00 - 7

• Anabolism: Small molecules are built into larger ones;

-

requires energy
-
nthesis dehydration
• Catabolism: Larger molecules are broken down into
O-so
- - -

smaller ones; releases energy hy drolysis

-
-
-
-
Y
-

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Anabolism and Catabolism

Anabolism:
-
Provides materials for maintenance, cellular
growth and repair; requires ATP made during catabolism;
-
-

example: Dehydration synthesis:

-

• Smaller molecules are bound together to form larger ones

nabolism
-
-

• H2O produced in the process

-
-
-

• Used to produce polysaccharides, proteins, triglycerides

--

Catabolism: Breaks down larger molecules into smaller

-
-

ones; -
---
ATP is produced; Example: Hydrolysis:
-

• Used to decompose carbohydrates, proteins, lipids

-

• Uses H2O to split the substances

-
-
-

• Reverse of dehydration synthesis

m
-
em
-

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Figure 4.2 Anabolism and Catabolism in Carbohydrates

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Figures 4.3 and 4.4 Anabolism and Catabolism in Fats
and Proteins

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4.2 Control of Metabolic Reactions
small-large
Marge-small
-

All cells perform catabolic and anabolic reactions

Rates of catabolism and anabolism must be carefully
controlled
Breakdown/energy-releasing reactions must occur at rates
that balance with build-up/energy-utilizing reactions
Imbalances in reaction rates can damage or kill a cell
Different types of cells conduct specialized metabolic
processes
Enzymes: Proteins
-
-

• Control rates of both catabolic and anabolic reactions

-
- - -

• Greatly increase reaction rates

-

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Enzyme Action

Enzymes (protein catalysts):

-
-

• Globular proteins that catalyze specific reactions

-

• Increase rates of chemical reactions

----

• Lower the activation energy necessary to start reactions

-----

• Not consumed in the reaction, so are used repeatedly

moleule
-

• Each enzyme is specific to a particular substrate

=
-

enzyme
ks on
• Ability to recognize substrate depends on shape of active
/
-- -
- - - -

site
-
of enzyme Where substrate
binds to
• Many enzymes are named after substrate, with “-ase” as
-

suffix; example: “lipase” breaks down lipids

-

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Figure 4.6 Enzyme Action

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From Science to Technology 4.1

The Human Metabolome

Metabolome: All small molecules that are part of the metabolism
in a cell, tissue, organ, or organism
• Human Metabolome Database stores vast amounts of
information about these molecules, also called “metabolites”
• Estimated that human cells have at least 2,500 metabolites, but
less than half have been identified
• Metabolites are being analyzed, and added to database to
record concentrations in different cells under various conditions,
pathways and enzymes that interact with them, drug and food
interfaces
• Information is being used in toxicology, drug discovery,
diagnosis, screening of newborns, transplant monitoring
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Enzymes and Metabolic Pathways

Metabolic Pathways:
• Series of enzyme-controlled reactions leading to formation of a
product
• Each new substrate is the product of the previous reaction
• Each step of a pathway is catalyzed by a different enzyme
• Rate-limiting enzyme:
• A regulatory enzyme that catalyzes one step of pathway typically sets rate
for entire reaction sequence
• Number of molecules of this enzyme is limited
• Often the first enzyme in the reaction sequence
• In some pathways, end product inhibits rate-limiting enzyme;
this is example of negative feedback enzymes work by
-

negative Feedback
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Figure 4.7 Metabolic Pathways

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Factors That Alter Enzymes

Cofactor:
-

• -
Non-protein substance
-
that combines
-
with the enzyme
-
to activate it
• Some help fold active site into proper conformation
• Some help bind enzyme to substrate
• Can be ion, element, or small organic molecule (coenzyme)
--
--

Coenzyme:
-

• Organic molecule that acts as cofactor

-
-
-

• Most are vitamins, which are essential organic molecules that humans
- - - -

must get from their diet

-
-

Denaturation:
-

• Inactivation of an enzyme (or any other protein), due to an irreversible

-
-
-

change in its conformation

-

• Results in enzyme being unable to bind to substrate

-
--

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Clinical Application 4.1

Inborn Errors of Metabolism

Deficient or absent enzyme blocks metabolic pathway that it
catalyzes
Results in accumulation of enzyme’s substrate, and a
deficiency of its product
Example: Phenylketonuria (PKU):
• Missing/nonfunctional enzyme blocks conversion of amino acid,
phenylalanine, into the amino acid, tyrosine
• Excess phenylalanine enters blood and poisons the brain
• Can be treated with special diet

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4.3 Energy for Metabolic Reactions

Energy:
-
-

• Capacity to change something, or the ability to do work

-----

• Common forms of energy: Heat, light, sound, electrical

-----

energy, mechanical energy, chemical energy

--
-

• Energy cannot be created or destroyed, but can be

-

changed from one form to another

-
- -

Cellular respiration:
-

• Process that transfers energy from molecules, and makes

----
- -

it available for cellular use

-

• Most metabolic reactions use chemical energy

-
- -

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Release of Chemical Energy

Many metabolic processes require chemical energy, which is -

stored in ATP
-

Energy is held in chemical bonds, and released when

-
-
- -

bonds are broken

-

Oxidation releases energy from glucose and other

molecules, via loss of hydrogen atoms and their electrons
In cells, enzymes lower activation energy needed for
- -

oxidation in reactions of cellular respiration

-

Energy is transferred to ATP:

•S40% is released as chemical energy
- -
- -

• O
60% is released as heat; maintains body temperature
- -
-
-

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ATP Molecules 1

cell energy
ATP (Adenosine Triphosphate):
-
- -
=

• Molecule that carries energy in a form the cell can use

- ----

• Main energy-carrying molecule in the cell; energy from

----

ATP breakdown is used for cellular work

- -
-
-

• Consists of 3 portions:
-
-
cleotide
a

• Adenine
-

• Ribose (a sugar)
-

• 3 phosphates in a chain
-
-

• Second and third phosphates are attached by high-energy

bonds; energy can be quickly transferred to other
molecules

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ATP Molecules 2

• When ATP loses terminal phosphate, it become

-

Adenosine
-
Diphosphate (A D P) (2)

• ADP can be converted back into A TP by attaching a third

-
- - -

phosphate; called phosphorylation

--

• Phosphorylation requires energy from cellular respiration

-----

• ATP and A DP cycle back and forth between cellular

respiration and energy-utilizing reactions

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Figures 4.8 and 4.9 ATP Molecules

08
S

Phosphorylation
S

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4.4 Cellular Respiration 1

Cellular Respiration of glucose occurs in 3 interconnected

reaction sequences:
- no Oxygen
• Glycolysis (anaerobic)
--

- -
-
takes place in
cytoplasm
requires oxygen
• Citric acid cycle (aerobic)
-
-

-
-

takes place in Mitochondria

- -

• Electron transport chain/oxidative phosphorylation

- - - -

(aerobic) ETC
-

Glycolysis and the Electron Transport Chain are stepwise

reaction sequences
Citric Acid Cycle occurs in a metabolic cycle in which the
final product reacts to replenish original substrate

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Process of Cellular Respiration

Cellular respiration of glucose requires a supply of glucose

and O2. Final products of cellular respiration:
-

• Carbon dioxide CO2

-

• Water H20
-
-

• ATP (chemical energy, 40%)

-
40% Atp
• HeatO
-
(60%) 60 % Heat
Includes 2 types of reactions:
• Anaerobic reactions: do not require O2, and make little
-
- -

ATP
-

• Aerobic
-
reactions:
-
require O2, and make
-
most of A TP

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Figure 4.10 A Metabolic Cycle

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Figure 4.11 Glucose Catabolism for every molewle of
glucose-36 ATP

Vitamin

NATH energy

suse +H
- +

-
is Enzyme
-

-
-
-
-I H+
· 0
- - -

Acetyl CoA

Oxaloacetic
- -

-
-
-

acid
-

o &
·
zCO2 +

Acetyl CoA

citric
-

-
-

-
-

- acid
-

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Glycolysis

Glycolysis:
-

• First reaction sequence of glucose breakdown

• Series of 10 reactions a 80 000
00

• Breaks down glucose-

-
-
>
(6-carbon) into 2 pyruvic acid (3-carbon)
molecules
-
- -

• Occurs in cytosol
-

• Anaerobic phase of cellular respiration

-
-

no oxygen

• Yields 2 ATP molecules -

-
per glucose molecule broken down
-

3 Phases of Glycolysis:
1. Phosphorylation of glucose
-

2. Splitting/cleavage of glucose into two 3-carbon molecules

- -

3. Production of NADH, ATP, and 2 molecules of pyruvic acid

-
-
⑧ o

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Figure 4.12 Glycolysis

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 Fermentation
Anaerobic Reactions takes H away from
ADH to make
at a
-

+
• In presence of O2, NADH and H deliver electrons to the electron
-----

transport
-
chain, with oxygen as final electron acceptor
• In absence of O2 , there is no electron acceptor
---

++ ++
• NADH and H deliver electrons and H back to pyruvic acid, to form
- - -

lactic acid
-

• Buildup of lactic acid inhibits glycolysis

-
- -

• ATP production is decreased

-
-
-

• Glycolysis produces much less ATP than aerobic respiration

- -

• There is net gain of 2 ATP per molecule of glucose broken down

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Aerobic Reactions

In presence of O2, pyruvic acid enters aerobic pathways

------

Aerobic reactions include:

• Synthesis of Acetyl Coenzyme A
-

• Citric acid cycle

-

• Electron
-
transport chain
Begins with pyruvic acid moving from cytosol to mitochondria
Pyruvic acid is used to produce Acetyl CoA
--

End products are CO2, H2O, and up to 36 ATP per molecule

-- -

of glucose
-

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Citric Acid Cycle

Citric Acid Cycle:

-

• 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 O2 are available

• For each citric acid molecule:
-

• 1 ATP is produced
-
+
• 8 hydrogen atoms are transferred to NAD and
- -
-
-

FAD
-

• 2 CO2 are produced; enters blood and is exhaled

-
- -

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Figure 4.13 Citric Acid Cycle

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Electron Transport Chain

NADH and FADH2 carry hydrogen and high-energy electrons to

-
- -

the Electron Transport Chain (ETC)

-
-
-

ETC is a series of enzyme complexes (electron carriers) located in -

the inner membrane of mitochondria

- - -

Energy from electrons is transferred to the enzyme ATP synthase

-
-
- -

ATP synthase uses energy to catalyze phosphorylation of ADP to

- -

ATP
-

H2O is formed (oxygen is the final electron “carrier”)

-
- - -

Summary of ATP production in complete oxidation of glucose:

• 2 ATP produced in glycolysis
- -

• 2 ATP in citric acid cycle

--

• 28 in electron transport chain

--

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Figure 4.14 ATP Synthesis in Oxidative Phosphorylation

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Carbohydrate Storage

Carbohydrate molecules from foods can:

• Enter catabolic pathways for energy production
-

• Enter anabolic pathways for storage

-

• React to form some amino acids

-

Excess glucose can be converted into and stored as:

- -

• Glycogen: Most cells, but liver and muscle cells store the
- -
-

most broken down into glucose

-

• Fat: For storage in adipose tissue

- -

glycerol

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Figure 4.15 Carbohydrate Storage

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Figure 4.16 Summary of Catabolism of Proteins,
Carbohydrates, and Fats

Red Tiger/Shutterstock RF

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4.5 DNA (Deoxyribonucleic Acid)

Deoxyribonucleic acid (DNA):

-

• The genetic material

-

• Molecule that stores information on its sequence of

----

nucleotides, that instructs a cell to how synthesize certain

--
- -

proteins
- -

• The proteins coded for on DNA function as:

-

• -
Enzymes
• -
Blood proteins
• Structural proteins of muscle and connective tissue
-
-
-

• Antibodies
-

• Cell membrane components

-

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Genetic Information

• Genetic information: Instructions to tell cells how to

--

construct proteins; stored in D NA sequence

--

• Gene: Sequence of DNA that contains information for

---

making 1 protein
-

• Genome: Complete set of genetic information in a cell

--

• Exome: Small portion of the genome that codes for

-
- -
-

proteins
-

• Gene Expression: Control of which proteins are produced

-

in each cell type, in what amount, and under which

-
- -

circumstances
--

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 Structure of DNA
--

Double helix:
-

• Double-stranded molecule, consisting of 2 chains of

-

nucleotides
-

• DNA resembles ladder twisted into a spiral

--

• Backbone of each strand is a sugar-phosphate chain

-
-

• Bases from the 2 complementary strands are linked -

together by hydrogen bonds: C

-
C ̶ GA
G, A ̶ T
T -
-

-
-

-
Nucleotides are building blocks of DNA, and consist of:
-
-
-
-

• 5-carbon sugar, deoxyribose Scarbon Sugar

- -
nucleotide
• A phosphate group phosphate group L

nitrogenous base
-

• A nitrogenous base (adenine, cytosine, guanine, or

-

thymine)
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Figure 4.17 Nucleotide Structure

nitrogenous
phosphate base
group
ribose
5 carbon
Sugar

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Figures 4.18 and 4.19 The Structure of DNA

hydrogen bonding
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DNA and Chromosome Structure

• 2 nucleotide chains of the double

- -
helix are antiparallel:
point in opposite directions
-

• Complementary Base Pairing: Bases pair only with

-

specific (A ̶ T and C ̶ G)
-

• A and G are purines, and C and T are pyrimidines

---
-

• A purine only binds to a specific pyrimidine

- -

• DNA wraps around histone proteins to give double helix

a compact form in chromatin and chromosomes

A+ G purines
C +
pyrimidines
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Figure 4.20 DNA and Chromosome Structure

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From Science to Technology 4.2

DNA Profiling Frees a Prisoner

Human genome contains 3.2 billion bits of information
DNA profiling/DNA fingerprinting compares the most
variable parts of genome among individuals
DNA profiling is used for:
1. Identifying human remains at crime scenes or natural disasters.

2. Checking for family relationships, paternity.

3. Establishing innocence in criminal cases, such as rape.

Hundreds of prisoners have been freed due to D NA profiling.

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DNA Replication

When cell divides, each daughter cell must receive identical

DN A
DNA Replication: process that produces an exact copy of a
- -

D NA molecule; occurs during interphase

- Sphase

Steps in DNA replication:

-

• Hydrogen bonds break between base pairs

--

• Strands unwind and separate

-
-
-

• New nucleotides pair with exposed bases, under direction

-
- - -

of DNA polymerase
-

• Other enzymes connect new sugar-phosphate backbone

-
-
-

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Figure 4.21 DNA Replication

DNA polymerase
nucleotides

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4.6 Protein Synthesis

• A sequence of 3 nucleotides provides template for

complementary RNA
• Each unit of 3 RNA nucleotides represents genetic code
-

• Sequence of bases in a gene determines the amino acid

sequence in a polypeptide
• Each sequence of 3 nucleotides either represents an
amino acid or signals to start or stop protein synthesis
• Protein synthesis involves processes of transcription and
translation

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RNA Molecules
-

RNA differs from DNA in following ways:

-
-

• Single strand of nucleotides

-
- -

• Contains the sugar, G

-
ribose, instead of deoxyribose
-

• One of the nucleotide bases is different: RNA contains

Uracil (instead of Thymine), but the other 3 bases are the
-

same (Adenine, Guanine, and Cytosine)

V A -C G
- -

• Much shorter than DNA

-
-

• There are different types of RNA: Messenger RNA

- -

(mRNA),Transfer RNA (tRNA), and Ribosomal RNA

- - -

(rRNA)
-

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Figure 4.22 RNA Structure

A Y -

C -

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 RNA
-
messengeh
Transcription

• DNA (deoxyribonucleic acid) stores master copy of

-
-

genetic code, and remains in the nucleus

-

• Protein synthesis occurs in cytoplasm

- -

• RNA (ribonucleic acid) copies and transfers information

-

from DNA to the cytoplasm

-

• Transcription: Process of copying DNA sequence onto an

RNA sequence
• Messenger RNA (mRNA): The type of RNA that carries
- -
·
Cyto

genetic code from DNA to ribosome in cytoplasm

- -

• RNA Polymerase: Enzyme that catalyzes the formation of

-
- -

mRNA from the proper strand of D NA

- -

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Steps in Transcription mRNA makes copy of a

Transcription DNA strand in nucleus

Steps in Transcription of mRNA:
• RNA polymerase recognizes correct strand of DNA to copy
-

• RNA polymerase binds to Promoter, the DNA sequence that

- -
-

signals beginning of a gene

-

• A section of DNA unwinds to expose the gene coding for the

-
-

particular protein
-

• Complementary mRNA nucleotides pair with the DNA bases

-
-
- -
-

• Termination signal indicates end of gene

-
- -

• New mRNA strand is released, and DNA rewinds into double

---

helix
-

• The mRNA now leaves the nucleus through a nuclear pore, and
-
-
attaches to a ribosome in the cytoplasm
-
- -

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Figure 4.23 Transcription of mRNA

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 proteins
Translation 1 binds to
-

+RNA w/ anticodon mRNA

codon

• Each amino acid is specified by a sequence of 3 bases in

-
-

DNA, called&
-
codons
• Protein synthesis occurs inO
me
cytoplasm -

• mRNA leaves nucleus and binds to ribosome, to act as

- -

template for protein synthesis

• At the ribosome, the genetic code, carried by mRNA, is
used to synthesize a protein
• Translation: Process of converting the genetic code,
-

carried by mRNA, into a sequence of amino acids that

--

becomes a protein
-

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Figure 4.24 Protein Synthesis
Codon = 3 bases

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Translation 2

• Protein synthesis requires that amino acids are added to -

growing polypeptide chain in proper sequence

-

• Transfer RNA (tRNA) aligns amino acids during

-

translation, along the mRNA strand on the ribosome

-

• tRNA binds to its amino acid, transports it to a ribosome,

binds to the mRNA according to its sequence, and adds its
amino acid to the growing polypeptide chain
• Each tRNA contains a sequence of 3 nucleotide bases,
- -

the anticodon, which binds to the complementary codon

- -

on the mRNA strand

-
-

• As the ribosome moves down mRNA, each tRNA brings in

its amino acid to be added to the growing protein
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Translation 3

• There are 20 types of amino acids

• There are 64 possible codons (3-base sequences) on
-

mRNA
• Most codons correspond to amino acids Auc
Methionine
• 1 to 4 mRNA codons code for each amino acid
• The Initiation codon,G
-
-
AUG, codes for -
Methionine and -

signals the start of a protein

-
UGA , vAG , UAA
• 3 codons are Stop codons, signaling the end of a protein;
-
-
-

these do not have corresponding tRNAs

• For each mRNA codon coding for an amino acid, there is a
corresponding tRNA anticodon
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Figure of Table 4.2 Codons (mRNA Three-Base 111I
Sequence)
IIII

....

.....

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Translation 4

Ribosomes:
• Organelles composed of Ribosomal RNA (rRNA) and protein
molecules
• Composed of 2 unequal subunits
• Binding of tRNA and mRNA occurs in association with a
ribosome
• Ribosome moves down mRNA molecule, bringing in tRNAs
carrying the proper amino acid to add to the growing protein
chain
• Amino acids are joined by peptide bonds
- - -

• When ribosome reaches a “stop” codon, the protein is released

- - -

• Ribosomes, mRNA, and rRNA can be used repeatedly

-

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Figure 4.25 The Process of Translation

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Table 4.3 Protein Synthesis
Transcription (In the Nucleus)
Inpolymerase
1. RNA the first part,
bindsthe rows
to the list
DNA thesequence
base steps inofTranscription
a gene. (in the
2. Thisnucleus). In the and
enzyme unwinds second part,
exposes the
part of rows listmolecule.
the DNA the steps in
translation
3. RNA polymerase(in the along
moves cytoplasm).
one strand of the exposed gene and catalyzes synthesis of
an mRNA, whose nucleotides are complementary to those of the strand of the gene.
4. When RNA polymerase reaches the end of the gene, the newly formed mRNA is released.
5. The DNA rewinds and closes the double helix.
6. The mRNA passes through a pore in the nuclear envelope and enters the cytoplasm.

Translation (In the Cytoplasm)

1. A ribosome binds to the mRNA near the codon at the beginning of the messenger strand.
2. A tRN A molecule that has the complementary anticodon brings its amino acid to the ribosome.

3. A second tRNA brings the next amino acid to the ribosome.

4. A peptide bond forms between the two amino acids, and the first tRNA is released.
5. This process repeats for each codon in the mRNA sequence as the ribosome moves along its
length, forming a chain of amino acids.
6. The growing amino acid chain folds into the unique conformation of a functional protein.
7. The completed protein molecule is released. The mRNA, ribosome, and tRNA are recycled.

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 4.7 Changes in Genetic Information

G
99.9% of human genome sequences are the same among all
- -
-

people
E
0.1% of the genome that varies among people includes: -

• DNA sequences that affect health

-

• DNA sequences that affect appearance

-

• DNA base variations that have no observable effects

- -

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Nature of Mutations 1

Mutations: Changes in the DNA sequence

----

Mutations occur when bases are changed, added, or deleted

- -
-

Mutations can be:

-

• Spontaneous: due to insertion of unstable base into DNA

-
- -
-

sequence
-
-

• Induced: due to exposure to mutagens, chemicals, or

-
- -
- --

radiation that cause mutation

-
-
-

mutations =
change in the DNA sequence

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Figure 4.26 The Mutation That Causes Sickle Cell
Disease

Access the text alternative for slide images.

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Nature of Mutations 2

• Some mutations are not harmful, and do not affect health.

• Many mutations affect health, by changing the amino acid
sequence, resulting in a nonfunctional or missing protein.
Example: Sickle cell disease is caused by a single
nucleotide substitution; this causes production of abnormal
hemoglobin, which causes change in shape of red blood
cells, in low-oxygen conditions, and extreme pain
• Rarely, a mutation provides an advantage to health.
Example: A mutation protects some people against HIV;
the receptor to which the virus binds is incomplete

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Protection Against Mutation

DNA Repair:
• Correction of a mismatched nucleotide by a Repair
Enzyme
• Nature of genetic code:
Since often 2 to 4 codons specify the same amino acid,
some mutations changing the third base of a codon would
result in production of the same amino acid, which would
not affect the protein
• Having 2 copies of each chromosome:
If one copy is mutated, the other copy may provide
enough of gene’s normal function to maintain health

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 End of Main Content

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