Transcript PowerPoint to accompany Hole’s Human Anatomy and

Harker Heights High School
BIOL 2401 / 7665A:
DUAL CREDIT ANATOMY & PHYSIOLOGY
CHAPTER 4: CELLULAR METABOLISM
Barton R Jacques
Professor
Dept. of Biology
1
4.1: Introduction
• 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
2
4.2: Metabolic Processes
• Consists of two processes:
Anabolism = synthesis reactions
building complex molecules from simpler ones
bonds are formed between monomers which
hold energy (Endergonic rx)
ex. Dehydration synthesis
Catabolism = decomposition reactions
breaking complex molecules into simpler ones
bonds are broken between monomers releasing
energy (Exergonic rx)
ex. hydrolysis
3
Anabolism
• 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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
CH2OH
CH2OH
O
H
O
H
H
CH2OH
H
O
H
H
CH2OH
H
O
H
H
H
H
H
H2O
HO
OH
H
H
OH
HO
OH
Monosaccharide
+
OH
H
H
OH
Monosaccharide
OH
HO
OH
H
H
OH
O
Disaccharide
OH
H
H
OH
+
OH
Water
4
Anabolism
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
H
H
H
O
C
OH
HO
C
(CH2)14 CH3
H
O
C
O
O
H
C
OH
HO
C
C
OH
HO
C
(CH2)14 CH3
O
(CH2)14 CH3
H
C
O
O
H
C
C
H2O
H2O
H2O
(CH2)14 CH3
O
(CH2)14 CH3
H
H
C
O
C
(CH2)14 CH3
H
+
Glycerol
3 fatty acid molecules
+
Fat molecule (triglyceride)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
3 water
molecules
Peptide
bond
H
H
N
H
C
C
R
Amino acid
H
H
O
N
O
H
H
+
C
H
O
C
R
Amino acid
N
O
H
H
H
O
C
C
R
R
N
C
H
H
Dipeptide molecule
O
C
OH
H2O
+
Water
5
Catabolism
• 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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
CH2OH
CH2OH
O
H
O
H
H
CH2OH
H
O
H
H
CH2OH
H
O
H
H
H
H
H
H2O
HO
OH
H
H
OH
HO
OH
Monosaccharide
+
OH
H
H
OH
Monosaccharide
OH
HO
OH
H
H
OH
O
Disaccharide
OH
H
H
OH
+
OH
Water
6
Catabolism
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
H
H
H
O
C
OH
HO
C
(CH2)14 CH3
H
O
C
O
O
H
C
OH
HO
C
C
OH
HO
C
(CH2)14 CH3
O
(CH2)14 CH3
H
C
O
O
H
C
C
H2O
H2O
H2O
(CH2)14 CH3
O
(CH2)14 CH3
H
H
C
O
C
(CH2)14 CH3
H
+
Glycerol
3 fatty acid molecules
+
Fat molecule (triglyceride)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
3 water
molecules
Peptide
bond
H
H
N
H
C
C
R
Amino acid
H
H
O
N
O
H
H
+
C
H
O
C
R
Amino acid
N
O
H
H
H
O
C
C
R
R
N
C
H
H
Dipeptide molecule
O
C
OH
H2O
+
Water
7
4.3: Control of Metabolic
Reactions
• 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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Substrate molecules
Product molecule
Active site
Enzyme
molecule
(a)
Enzyme-substrate
complex
(b)
(c)
Unaltered
enzyme
molecule
8
Enzyme Action
• Metabolic pathways
• Series of enzyme-controlled reactions leading to formation of a
product
• Each new substrate is the product of the previous reaction
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Substrate
1
Enzyme A
Substrate
2
Enzyme B
Substrate
3
Enzyme C
Substrate
4
Enzyme D
Product
• Enzyme names commonly:
• Reflect the substrate
• Have the suffix – ase
• Examples: sucrase, lactase, protease, lipase
9
Factors affecting rate of
Chemical RXs
Particle size – the smaller the particle, the faster the
reaction will occur.
Temperature- the higher the temperature, the faster the
reaction will occur (up to a point)
Concentration- the greater number of particles in a given
space, the faster the reaction
Catalysts-enzymes in the biological system
In most metabolic pathways, the end-product comes back
and inhibits the first enzyme (ie. the rate-limiting
enzyme)
10
Cofactors and Coenzymes
• The active site of an enzyme may not always be exposed
(recall the 3D structure of proteins)
•Cofactors or coenzymes may be necessary to “activate” the
enzyme, so it can react with the substrate.
•Cofactors
• Make some enzymes active
• Non-protein component
• Ions of a metal (minerals like Fe, Cu, and Zn)
• Coenzymes
• Organic molecules that act as cofactors
• Vitamins (primarily B vitamins)
11
Factors That Alter Enzymes
• Factors that alter enzymes:
Enzymes can become inactive or even denature in extreme
conditions
• Heat
• Radiation
• Electricity
• Chemicals
• Changes in pH
12
Regulation of Metabolic
Pathways
• Limited number of regulatory enzymes
• Negative feedback – in most metabolic pathways, the
end product comes back and inhibits the first enzyme
•ie. The rate limiting enzyme
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Inhibition
Rate-limiting
Enzyme A
Substrate
Substrate
2
1
Enzyme B
Substrate
3
Enzyme C
Substrate
4
Enzyme D
Product
13
4.4: Energy for Metabolic
Reactions
• 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
All metabolic reactions involve some form of energy
14
ATP Molecules
• Each ATP molecule has three parts:
• An adenine molecule
• A ribose molecule
• Three phosphate molecules in a chain
P
P
Energy transferred
and utilized by
metabolic reactions
when phosphate bond
is broken
Energy transferred from
cellular respiration used
to reattach phosphate
P
P
P
P
P
15
Energy for Metabolic Rxs
 The triphosphate tail of ATP is unstable.
 The bonds between the phosphate groups can be
broken by hydrolysis releasing chemical energy
 Exergonic rx.
A molecule of inorganic phosphate (Pi) and ADP are
the products of the REACTION:
ATP----Adenosine Diphosphate (ADP) + Pi
The inorganic phosphate from ATP can now be
transferred to some other molecule which is now
said to be “phosphorylated”.
16
Energy for Metabolic RXs
 ADP can be regenerated by the addition of a
phosphate in an endergonic rx.
 ADP + Pi ------------ATP
 ADP and ATP shuttle back and forth between the
energy releasing reactions of CR and the energy
utilizing reactions of the cell.
If ATP is synthesized by direct phosphate
transfer the process is called –substrate level
phosphorylation.
17
Release of Chemical Energy
• Most metabolic rx depend on chemical energy
•Energy is held within the chemical bonds that link atoms
to molecules
•When the bonds break, chemical energy is released
•This release of chemical energy is termed oxidation
In cells, enzymes initiate oxidation by:
•decreasing activation energy
•transferring energy to special energy-carrying
molecules called coenzymes.
18
4.5: Cellular Respiration
•
•
•
CR is how animals cells use oxygen to release chemical
energy from food to generate cellular energy (ATP)
CR must occur in a particular sequence, with each rx being
catalyzed by a different specific enzyme.
The three major series of rxs:
1. Glycolysis
2. Citric acid cycle (aka TCA or Kreb’s Cycle)
3. Electron transport system
Some enzymes are present in the cell’s cytoplasm, so those
rx occur in the cytosol, while other enzymes are present
in the mitochondria and
19
Cellular Respiration
• Produces:
• Carbon dioxide
• Water
• ATP (chemical energy)
• Heat
•All organic molecules (carbo, fats, and proteins) can be
processed to release energy, but we will only study the
steps of CR for the breakdown of glucose.
•Includes:
• Anaerobic reactions (without O2) - produce little ATP
• Aerobic reactions (requires O2) - produce most ATP
20
Glycolysis
• 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. Phosphorylation
2. Splitting
3. Production of NADH and ATP
21
Glycolysis
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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
Glucose
Phase 1
priming
Carbon atom
P Phosphate
2 ATP
2 ADP
Fructose-1,6-diphosphate
P
P
Phase 2
cleavage
Dihydroxyacetone
phosphate
P
Phase 3
oxidation and
formation of
ATP and release
of high energy
electrons
Glyceraldehyde
phosphate
P
P
2 NAD+
4 ADP
2 NADH + H+
4 ATP
2 Pyruvic acid
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
22
Cellular Respiration
 Most of the energy is lost as heat
 Almost half of the energy is stored in a form
the cell can use, as ATP
 For every glucose molecule that enters CR usually
36 ATP are produced, however up to 38 ATP can
be generated.
23
Oxidation: Reduction (Of CR)
 Many of the reactions in the breakdown of
glucose involve the transfer of electrons (e-)
 Reactions are called oxidation – reduction
(or redox reactions)
Glucose is oxidized(loses e- and H); Oxygen is
reduced (gains e- and H)
In a redox rx:
loss of electrons is called oxidation
addition of electrons is called reduction
24
Redox RX
 An electron transfer can involve the transfer
of a pair of hydrogen atoms from one
substance to another.
 The H atoms (and e-) are eventually transferred to
oxygen
 The transfer occurs in the final step of CR
 In the meantime, the H atoms (w/ e-) are passed
onto a coenzyme molecule (ie. NAD+
nicotinamide adenine dinucleotide) or FADH
(flavin adenine dinucleotide)
25
Redox Rx…cont
 H:H + NAD+ = NADH + H+
 H:H + FADH = FADH2 + H+
 This is coenzyme reduction
In the final step of CR:
 The electron transport chain
 Oxygen is final electron acceptor (forming water)
 NADH or FADH2 are oxidized; back to their
original form
 The energy released is used to syn ATP
 This is called oxidative phosphorylation
26
Glycolysis
 Means “splitting of sugar”
 A six carbon sugar is split into 2 3-C molecules
 Occurs in the cytoplasm of the cell
 Oxygen is not required (ie. Anaerobic)
 Energy yield is:
 2 net ATP per glucose molecule, substrate level
phosphorylation
 2 NADH (stored electrons for ETS)
Many steps are required, and each is catalyzed by a
different specific enzyme
27
Anaerobic Reactions
 Recall that glycolysis results in pyruvate. If
oxygen is not present (ie. Anaerobic) pyruvate
can ferment in one of two ways:
 1. Lactic Acid fermentation
 Pyruvate is converted to lactic acid–waste product
 Occurs in many animal muscle cells
 Serves as an alternate method of generating ATP
when oxygen is scarce; causes muscle soreness
and fatigue
28
Anaerobic Respiration …cont
 Alcohol fermentation
 Pyruvate is converted to ethanol
 Occurs in yeast (brewing and backing)
 And many bacteria
 This is why we use yeast for baking and
brewing
“The yeasties are the beasties that consume
sugars and pass gas and alcohol…”
29
Glycolysis
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Glucose
Phase 1
priming
Carbon atom
P Phosphate
2 ATP
2 ADP
Fructose-1,6-diphosphate
P
P
Phase 2
cleavage
Dihydroxyacetone
phosphate
P
Phase 3
oxidation and
formation of
ATP and release
of high energy
electrons
Glyceraldehyde
phosphate
P
P
2 NAD+
4 ADP
2 NADH + H+
4 ATP
2 Pyruvic acid
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
30
Anaerobic Reactions
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• 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
Glucose
Phase 1
priming
Carbon atom
P Phosphate
2 ATP
2 ADP
Fructose-1,6-diphosphate
P
P
Phase 2
cleavage
Dihydroxyacetone
phosphate
P
Phase 3
oxidation and
formation of
ATP and release
of high energy
electrons
Glyceraldehyde
phosphate
P
P
2 NAD+
4 ADP
2 NADH + H+
4 ATP
2 Pyruvic acid
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
31
Aerobic Respiration
 Conversion of Pyruvate to Acetyl CoEnz A
Under aerobic conditions (when O2 is present)
a. Pyruvate enters the mitochondrion
usu requires 1 ATP per pyruvate
b. Pyruvate (3-C) is converted to acetyl CoA (2-C)
The carbon is released as CO2
c.Energy yield is 1 NADH per pyruvate in this step
(2 NADH per glucose)
d. See Fig. 4.11 pg. 123
32
Aerobic Reactions
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• 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
Glucose
High energy
electrons (e–) and
hydrogen ions (H+)
2 ATP
Pyruvic acid Pyruvic acid
Cytosol
Mitochondrion
High energy
electrons (e–) and
hydrogen ions (h+)
CO2
Acetyl CoA
Oxaloacetic
acid
Citric acid
High energy
electrons (e–) and
hydrogen ions (H+)
2 CO2
2 ATP
Electron transport chain
32-34 ATP
O2
–
+
2e + 2H
H2O
33
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 oxygen are
available
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Pyruvic acid from glycolysis
Cytosol
CO2
Carbon atom
P
NAD+
Phosphate
Mitochondrion CoA Coenzyme A
NADH + H+
Acetic acid
CoA
Acetyl CoA
(replenish molecule)
Oxaloacetic acid
Citric acid
(finish molecule)
(start molecule)
CoA
NADH + H+
NAD+
Malic acid
Isocitric acid
NAD+
• For each citric acid molecule:
• One ATP is produced
• Eight hydrogen atoms are
transferred to NAD+ and
FAD
• Two CO2 produced
Citric acid cycle
CO2
Fumaric acid
NADH + H+
-Ketoglutaric acid
CO2
CoA
NAD+
FADH2
NADH + H+
FAD
Succinic acid
CoA
Succinyl-CoA
ADP + P
ATP
34
Electron Transport System
• 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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
ADP + P
ATP synthase
ATP
Energy
NADH + H+
Energy
2H+ + 2e–
NAD+
Energy
FADH2
2H+ + 2e–
FAD
Electron transport chain
2e–
2H+
O2
H2O
35
Summary of Cellular
Respiration
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Glucose
Glycolysis
High-energy electrons (e–)
2 ATP
Glycolysis
Cytosol
1 The 6-carbon sugar glucose is broken down in the
cytosol into two 3-carbon pyruvic acid molecules with
a net gain of 2 ATP and release of high-energy
electrons.
Pyruvic acid
Pyruvic acid
Citric Acid Cycle
2 The 3-carbon pyruvic acids generated by glycolysis
enter the mitochondria. Each loses a carbon
(generating CO2 and is combined with a coenzyme to
form a 2-carbon acetyl coenzyme A (acetyl CoA). More
high-energy electrons are released.
High-energy electrons (e–)
CO2
Acetyl CoA
Citric acid
Oxaloacetic acid
Mitochondrion
3 Each acetyl CoA combines with a 4-carbon oxaloacetic
acid to form the 6-carbon citric acid, for which the cycle
is named. For each citric acid, a series of reactions
removes 2 carbons (generating 2 CO2’s), synthesizes
1 ATP, and releases more high-energy electrons.
The figure shows 2 ATP, resulting directly from 2
turns of the cycle per glucose molecule that enters
glycolysis.
Citric acid
cycle
High-energy electrons (e–)
2 CO2
2 ATP
Electron Transport Chain
4
The high-energy electrons still contain most of the
chemical energy of the original glucose molecule.
Special carrier molecules bring the high-energy
electrons to a series of enzymes that convert much of
the remaining energy to more ATP molecules. The
other products are heat and water. The function of
oxygen as the final electron acceptor in this last step is
why the overall process is called aerobic respiration.
Electron
transport
chain
32–34 ATP
2e– and 2H+
O2
H2O
36
Carbohydrate Storage
• Carbohydrate molecules from foods can enter:
• Catabolic pathways for energy production
• Anabolic pathways for storage
37
Carbohydrate Storage
• Excess glucose stored as:
• Glycogen (primarily by liver and muscle cells)
• Fat
• Converted to amino acids
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Carbohydrates
from foods
Hydrolysis
Monosaccharides
Catabolic
pathways
Anabolic
pathways
Energy + CO2 + H2O Glycogen or Fat
Amino acids
38
Summary of Catabolism of
Proteins, Carbohydrates, and
Fats
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Food
Proteins
(egg white)
Carbohydrates
Carbohydrates
(toast,
(toast,hashbrowns)
hashbrowns)
Amino acids
Fats
(butter)
Simple sugars
(glucose)
Glycolysis
Glycerol
Fatty acids
ATP
2 Breakdown
Breakdownofofsimple
simple
molecules
moleculestotoacetyl
acetyl
coenzyme
coenzymeAA
accompanied
accompaniedby
by
production
productionofoflimited
limited
ATP
ATPand
andhigh
highenergy
energy
electrons
electrons
Pyruvic acid
Acetyl coenzyme
coenzyme A
A
Acetyl
Citric
acid
cycle
3 Complete oxidation
of acetyl coenzyme A
to H2O and CO2 produces
high energy electrons
(carried by NADH and
FADH2), which yield much
ATP via the electron
transport chain
CO2
ATP
ATP
High
High energy
energy
electrons
electrons carried
carried
by
NADH
by NADH and
and FADH
FADH22
Electron
Electron
transport
transport
chain
chain
1 Breakdown
Breakdown
ofoflarge
large
macromolecules
macromolecules
totosimple
simplemolecules
molecules
ATP
2e– and 2H+
–NH2
CO2
½ O2
H2O
Waste products
© Royalty Free/CORBIS.
39
Nucleic Acids and
Protein Synthesis
• Enzymes regulate metabolic pathways that allow cells to
survive; therefore, cells must have the information
for producing these special proteins…
Genetic Information
DNA holds the genetic information and is passed
from parents to their offspring
DNA contains the blueprint for the construction of
the proteins necessary for cell survival
Gene – portion of DNA molecule that codes for one
kind of protein
Genome – all of the DNA in a cell
40
Deoxyribonucleic Acid (DNA)
• DNA is composed of nucleotides
A pentose sugar molecule – deoxyribose
A nitrogen-containing base
Purines (double ring)
adenine (A)
guanine (G)
Pyrimidine (single ring)
cytosine (C)
thymine (T)
A phosphate group -
41
Deoxyribonucleic Acid (DNA)
Each DNA strand is made up of a backbone of deoxyribose sugars
alternating with phosphate groups
Each deoxyribose sugar is linked to one of four nitrogenous bases –
AGCT
Each DNA molecule consists of two parallel strands of nucleotides
running in opposite directions
The two strands are twisted into a double helix
42
DNA Replication
During Interphase of the cell cycle, DNA is replicated so
that each daughter cell is provided an identical copy of
the genetic material
Process of DNA Replication:
1. DNA uncoils and unzips (H bonds broken between A:T and
C:G)
2. DNA nucleotides that are present in the nucleoplasm begin to
match up with their complements on the template
(DNA polymerase positions and links nucleotides into
strands)
3. This results in two identical DNA molecules, each consisting of
one old and one new nucleotide strand (semi-conservative)43
Structure of DNA
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
(a) Hydrogen
bonds
P
C
G
Thymine (T)
Adenine (A)
Cytosine (C)
Guanine (G)
P
P
T
P
P
C
G
P
P
G
P
C
P
A
P
• 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
A
Nucleotide strand
G
C
T
C
Segment
of DNA
molecule
G
A
(b)
Globular
histone
proteins
Chromatin
Metaphase
chromosome
(c)
44
DNA Replication
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
A
• Hydrogen bonds break
between bases
• Double strands unwind
and pull apart
• New nucleotides pair
with exposed bases
• Controlled by DNA
polymerase
T
C
G
G
C
C
G
T
A
Original DNA
molecule
C
G
C
G
A
T
A
C
T
G
A
T
G
C
C
Region of
replication
G
T
T
A
T
A
A
A
A
T
G
C
T
G
A
C
C
T
T
A
T
G
G
G
A
Newly formed
DNA molecules
C
G
A
45
Genetic Code
• Specification of the correct sequence of amino acids in a
polypeptide chain
Each Triplet (three adjacent nucleotides) codes for an amino acid
Many triplets code for many amino acids, which are linked
together to form a polypeptide chain
RNA molecules facilitate the conversion of DNA triplets to an
amino acid sequence
46
Ribonucleic Acid (RNA)
RNA (like DNA) is composed of nucleotides, each containing the
following:
a pentose sugar (ribose)
a nitrogenous base
Purine – adenine (A) or guanine (G)
Pyrimidine – cytosine (C) or uracil (U)
a phosphate group
RNA is a single stranded nucleotide
47
RNA Molecules
• Messenger RNA (mRNA):
• Making of mRNA (copying of DNA) is transcription
• 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
48
RNA Molecules
• Messenger RNA (mRNA):
• Delivers genetic information
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
from nucleus to the cytoplasm
DNA
• Single polynucleotide chain
P
• Formed beside a strand of DNA
P
S
A
U
T
A
G
C
P
S
Direction of “reading” code
• RNA nucleotides are
complementary to DNA
nucleotides (exception – no
thymine in RNA; replaced with
uracil)
RNA
S
P
S
S
P
P
S
S
P
C
G
G
C
P
S
S
P
S
P
49
Protein Synthesis
 Protein synthesis can be divided into two major steps
 Transcription
 Translation
Transcription
1. occurs in the nucleus
2. is the process of copying the information from a DNA
molecule and putting into a form of a mRNA molecule
3. the DNA strand unwinds and the H-bonds between the strands
are broken; only one of the exposed templates of DNA is
used to build the mRNA strand
RNA polymerase positions and links RNA nucleotides into a
strand
50
Protein Synthesis
4. the mRNA is complementary to the bases on the DNA strand
ie. DNA – TACGATTGCCAA
RNA – AUGCUAACGGUU
is in the form of a triple base code, represented by
codons/triplets ( ie. AUG, CUA, ACG, GUU)
each codon on mRNA codes for one amino acid in the
protein to be synthesized
can now leave the nucleus and travel to the ribosome, the
protein synthesizing machinery
51
Protein Synthesis
Translation
1. is the process by which the mRNA is “translated” into a
protein
2. occurs at ribosomes that are either free floating in the
cytoplasm or attached to the ER
3. can only start at the “start codon” AUG, which codes for
methionine
4. tRNA molecules assist in translation by bringing the
appropriate amino acid for each codon to the
ribosome
*tRNA has an anti-codon which is complimentary to
the mRNA codon
52
Protein Synthesis
Translation …cont
5. two codons of mRNA are read in a ribosome at a time
* tRNA delivers the amino acids to the ribosome, and
a peptide bond is formed between adjacent
amino acids
* mRNA molecule is read codon by codon
* the result is a polypeptide or protein molecule
6. mRNA molecule is read until a stop codon (UAA, UAG or
UGA) on mRNA is reached:
*The protein is released into the cytoplasm
*mRNA can be read again and again.
53
Protein Synthesis
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DNA
double
helix
Cytoplasm
Nucleus
T A
G C
A T
T A
G C
A T
GC
A T
C G
T A
CG
T A
G C
A T
GC
A T
C G
T A
CG
T A
G C
A T
GC
A T
C G
T A
CG
T A
3 Translation begins as tRNA anticodons
recognize complementary mRNA codons,
thus bringing the correct amino acids into
position on the growing polypeptide chain
6
2 mRNA leaves
the nucleus
and attaches
Messenger
to a ribosome
RNA
A T
U A
G C
G
G C
G
G C
C
C G
T
U A
C
C G
C
C G
G
C G
C G
C
A
A T
A
A T
C
C G
G C
G
G
G C
C G
C
A T
A
G
G C
G
G C
C G
C
U A
T
C
C G
C
C G
A
A T
T
U A
G
G C
A T
A
C
C G
G C
DNA
strands
pulled
apart
T
Amino acids
attached to tRNA
Polypeptide
chain
tRNA molecules
can pick up another
molecule of the
same amino acid
and be reused
G
5 At the end of the mRNA,
the ribosome releases
the new protein
Nuclear
pore
1 DNA
information
is copied, or
transcribed,
into mRNA
following
complementary
base pairing
Messenger
RNA
G C
Transcription
(in nucleus)
DNA
strand
G
C
C
G
A
T
C
G
G
C
C
G
U
C
A
G
4 As the ribosome
moves along the
mRNA, more amino
acids are added
Translation
(in cytoplasm)
Amino acids
represented
A
U
G
G
G
C
U
C
C
G
C
A
A
C
G
G
C
A
G
G
C
Codon 1
Methionine
Codon 2
Glycine
Codon 3
Serine
Codon 4
Alanine
Codon 5
Threonine
Codon 6
Alanine
Codon 7
Glycine
54
The Genetic Code…
mRNA codon chart
55
Changes in
Genetic Information
We are more alike than different:
*Human genome sequences are 99.9% the same among
individuals
*.1% of the human genome vary from person to person and
include rare DNA sequences that affect health
or appearance, as well as common DNA base
variations that do not exert an noticable effects
A mutation is a change in the genetic information in our genome.
56
Changes in
Genetic Information
Mutations are rare distinctions in DNA sequences (genes) that alter
health and or appearance
Common genetic variants with no detectable effects are called
single nucleotide polymorphisms (SNP’s – or snips)
* polymorphism means many forms
Mutations to genes are caused by a variety of sources called
mutagens
* including UV rays, hair dyes, smoked meats, food additives
57
Changes in
Genetic Information
Mutations may be spontaneous or induced
*spontaneous mutations occur from unstable form of a
nitrogenous base being inserted into the DNA
molecule
* induced mutations occur as a response to exposure to
certain chemicals or radiation
DNA changes are transmitted when the cell divides
* if these changes occur in egg or sperm cell the mutation is
tranmitted to the offspring
A protein synthesized from an altered DNA sequence may or may
not function normally
58
Nature of Mutations
• Mutations – change in genetic
information
• Result when:
• Extra bases are added or
deleted
• Bases are changed
• May or may not change the
protein
Direction of “reading” code
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Code for
glutamic
acid
T
P
Mutation
P
S
P
P
S
A
S
C
P
S
(a)
T
S
T
P
Code for
valine
C
S
(b)
59
Mutations and Disease
An enzyme may not be made at all…
when an enzyme is lacking from a metabolic pathway,
childhood storage diseases (accumulation of a substrate)
results ie. PKU and Tay-Sachs disease
A protein may have altered functions…
ex. Cystic fibrosis (altered chloride pump)
sickle cell anemia ( altered hemoglobin structure)
A protein may be produced in excess…
ex. in epilepsy where excess GABA leads to excess
norepinephrine and dopamine
60
Protection against Mutation
Usually “repair enzymes” prevent mutations by correcting
the DNA sequence
* remove mismatched nucleotides and fill the
resulting gap with the accurate,
complementary nucleotide
This is called the DNA damage response- restores the
original structure of the DNA molecule
(exception – Xeroderma pigmentosum)
The genetic code protects against some mutations…
ie. Changes in the third codon base
(ex. GGA to GGG)
Changes in the second codon base
61