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CELLULAR
METABOLISM
BIO 137 Anatomy & Physiology I
Metabolism
• The total of all chemical reactions in an organism
that are necessary to maintain life
• Includes synthesis and breakdown of molecules
• These reactions are usually stepwise and are called metabolic
pathways
• 2 Processes in Metabolism
• Catabolism
• Anabolism
Metabolic Pathways
• Catabolism
• Breakdown of larger molecules through Hydrolysis
• Exergonic (energy can be used to drive anabolic pathways)
• Example: oxidation (breakdown) of glucose in cellular
respiration
Metabolic Pathways
• Anabolism
• Construction of larger molecules (polymers) from
monomers through Dehydration
• Endergonic – requires energy
• Example: building a polypeptide chain and protein from
amino acids
Metabolic Pathways
• Reactant(s) → Product(s)
• Stepwise
• Each step in a pathway is catalyzed by a specific enzyme
• Enzymes are protein catalysts
• A substrate is what an enzyme acts on
• Each enzyme is specific for a substrate
Enzyme 1
A
Enzyme 3
D
C
B
Reaction 1
Starting
molecule
Enzyme 2
Reaction 2
Reaction 3
Product
Activation Energy, EA
• In a chemical reaction, bonds are broken in
reactants, requiring an initial energy investment
• EA – amount of energy needed to break bonds in
reactants
• EA is usually heat from surroundings
Enzymes
• Enzymes are protein catalysts that speed up the rate of a
reaction without being consumed
• Enzymes are necessary because most reactions proceed very
slowly and metabolism would be hindered
• A single enzyme can catalyze thousands of reactions a second
Enzyme-Substrate Binding
• Enzymes are PROTEINS with specific 3-dimensional
conformations (shape)
• Shape of enzyme determines function (what substrate it
will bind)
• Active site – region of an enzyme that binds a substrate
• Substrate ‘fits’ active site, forming enzyme-substrate
complex
• Lock and key model
• In this form, enzyme converts substrate to product**
Catalytic Cycle of an Enzyme
1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates
Enzyme-substrate
complex
6 Active site
is available for
two new substrate
molecules.
Enzyme
5 Products are
Released.
Products
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 Active site (and R groups o
its amino acids) can lower EA
and speed up a reaction by
• acting as a template for
substrate orientation,
• stressing the substrates
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
4 Substrates are
Converted into
Products.
Enzyme Activity is affected by
Environment
• Enzymes have optimal conditions under which they work
• Optimal conditions favor correct conformation
• Any physical or chemical condition that affects an
enzyme’s 3-dimensional shape can affect enzyme activity
• Temperature, pH, chemicals
• These conditions can change protein conformation =
Denaturation
• Makes an enzyme inactive
WHY DO WE CARE SO
MUCH ABOUT ENZYMES?
Enzyme regulation is vital to the control of
metabolism.
Metabolic Regulation
• Metabolism is controlled by regulation of enzyme activity
1. Alter gene expression of enzyme
2. Regulate enzymes already present in a cell (Allosteric
Regulation)
Energy
• Energy is defined as the capacity to do work
• Includes kinetic energy and potential energy
• Energy can be transformed from one form to another
• Energy is used to fuel cellular work
Forms of Energy
• Kinetic Energy
• Energy of motion
• Light (photosynthesis), heat (random movement of atoms and
molecules), Pool cue
• Potential Energy (PE)
• Stored energy due to location or structure
• Chemical Energy
• PE stored in molecules as a result of the arrangement of atoms in
the molecule
Free Energy & Metabolism
• Chemical reactions can be classified based on
how energy is used
• Exergonic
• Energy is given off in the reaction
• Spontaneous
• Endergonic
• Energy is required to start the reaction
• Not spontaneous
Energy and Metabolism
• Nutrients have potential energy (chemical energy) due to
the arrangement of atoms
• Electrons in the bonds holding atoms together represent energy!!
• Energy can be given off when nutrients are broken down
• Chemical energy in glucose is converted to ATP energy
during Cellular Respiration
Electrons and Energy
• Loss of electrons in nutrients as they are broken
down allows for the production of ATP
• Very complicated, do not focus on details
• Know that electrons represent stored energy
• Electrons are shuttled in a cell by electron
carriers and ultimately given to O2, making H2O
• CO2 is lost in several steps along the way
• Waste product of metabolism
ATP
• Adenosine Triphosphate
• Energy molecule of our
cells
• Cells that require energy to
perform functions use ATP for
that energy
• Composed of 3 parts:
• Adenine molecule
• Ribose molecule
• 3 phosphate groups in a
chain
Cellular Respiration
• Breakdown of nutrients in the presence of oxygen
(aerobic) to yield ATP
• Involves shuttling of electrons from food to oxygen
• C6H12O6 + 6 O2 → 6CO2 + 6H2O + (38 ATP)
• Breakdown is stepwise
Carbohydrate Metabolism
• Glucose is not just an example we happen to
choose – it is indeed the body’s preferred source of
fuel
• During digestion, polysaccharides and
disaccharides are hydrolyzed into the
monosaccharides glucose (80%),
fructose, and galactose
• These three monosaccharides are absorbed into the villi
of the small intestine and carried to the liver
• hepatocytes convert galactose and fructose to glucose
Cellular Respiration
• 3 major steps
• Glycolysis
• Initial breakdown of glucose
• Cytosol, anaerobic
• Citric Acid Cycle (Krebs)
• Matrix of mitochondria, aerobic
• Electron Transport Chain (Oxidative
Phosphorylation)
• Cristae of mitochondria, aerobic
• This is where those electrons are used!
Glycolysis
• Glucose, C6H12O6, is broken down into 2-
pyruvate molecules (3C)
• Stepwise, where electrons are given off to
electron carriers
• These are used in the Electron Transport Chain
• Occurs in the cytosol under Anaerobic
conditions
• ATP is both consumed and made here
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
Glycolysis
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
Net
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
Citric Acid Cycle (Krebs)
• Cycle where starting reactants are regenerated
• Cycle is completed 2X per glucose molecule
• Stepwise, where electrons are given off to electron carriers
• These are used in the Electron Transport Chain
• ATP is made
• CO2 is formed as waste
RECALL THAT ELECTRONS
REPRESENT STORED
ENERGY
Now we will use that stored energy to
make ATP!
Electron Transport Chain
• **Energy found in electron carriers is now used to make
ATP through oxidative phosphorylation
• Occurs on mitochondrial cristae
• Electrons are ultimately given to Oxygen and water is
formed
• Energy given off during this process is used to make ATP!
Electron Transport Chain
ATP
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
P
Energy transferred
from cellular
respiration used
to reattach
phosphate
P
P
ATP
P
ADP
P
P
Energy transferred
and utilized by
metabolic
reactions when
phosphate bond
is broken
P
Fermentation
• If oxygen is not present after glycolysis, pyruvate
is fermented
• Alcohol Fermentation
• Lactic Acid Fermentation
• Yeasts and some bacteria
• In animals
• Pyruvate is converted to
• Pyruvate is converted to
ethanol
lactic acid
• Accumulates and causes
muscle fatigue and
soreness
Fermentation
2 ADP + 2
Glucose
2 ATP
Pi
Glycolysis
O–
C
O
C
O
CH3
2 Pyruvate
2 NADH
+2 H+
2 NAD+
H
2 CO2
H
H C OH
C
CH3
O
CH3
2 Acetaldehyde
2 Ethanol
(a) Alcohol fermentation
2 ADP + 2
Glucose
P i
Glycolysis
2 NAD+
O
C O
H
C
2 ATP
OH
CH3
2 Lactate
(b) Lactic acid fermentation
2 NADH
O–
C
O
C
O
CH3
2 Pyruvate
Carbohydrate Storage
Excess glucose is stored as glycogen (liver and muscle cells)
• Can be converted to fat and amino acids
BREAKDOWN
BUILD UP
4-22
Fig. 4.15
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Food
Catabolism of
proteins, fats
and
carbohydrates
Proteins
(egg white)
Carbohydrates
(toast, hashbrowns)
Amino acids
Fats
(butter)
Simple sugars
(glucose)
Glycerol
Glycolysis
1
Breakdown of large
macromolecules
to simple molecules
2
Breakdown of simple
molecules to acetyl
coenzyme A
accompanied by
production of limited
ATP and high energy
electrons
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
Fatty acids
ATP
Pyruvic acid
Acetyl coenzyme A
Citric
acid
cycle
CO2
ATP
High energy
electrons carried
by NADH and FADH2
Electron
transport
chain
ATP
2e– and 2H+
–NH2
CO2
½ O2
H2 O
Waste products
© Royalty Free/CORBIS.
Central Dogma
Transcription
DNA
Translation
RNA
Protein
Replication
• DNA sequence contains information to direct protein
synthesis (MAKE A PROTEIN)
Genetics
• Genetic information inherited from our parents is
found in our DNA
• Gene
• Sequence of DNA nucleotides that codes for a protein
• DNA sequence contains information to direct protein synthesis
• Gene product = A protein
Genetics
• A Protein performs the function of the gene
• All of the DNA in a cell constitutes its genome
DNA Structure
• DNA is composed of
nucleotides
• DNA Nucleotide:
• Deoxyribose sugar
• Phosphate group
• Nitogen containing
base
• PURINE
• Adenine, A
• Guanine, G
• PYRIMIDINE
• Cytosine, C
• Thymine, T
DNA Structure
• DNA is double stranded
• Each strand is composed
of repeating nucleotides
• Joined together by
hydrogen bonds between
complimentary bases
• A binds T (2 H-bonds)
• G binds C (3 H-bonds)
• Sugar-phosphate backbone
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
(a)
Hydrogen
bonds
P
P
CC
G
Thymine (T)
Adenine (A)
Cytosine (C)
Guanine (G)
P
Fig. 4.19a
P
TT
P
P
P
CC
GG
P
P
P
C
P
G
P
A
P
G
C
A
Nucleotide strand
G
C
T
C
G
A
Segment
of DNA
molecule
DNA Replication
• Occurs in the nucleus
• DNA unwinds and is replicated before a cell divides
• Makes an identical copy of DNA using parental DNA
as a template
DNA Replication
• DNA Replication is semi-conservative
• Resulting DNA is half-old, half-new
• Parental DNA (template) and newly synthesized DNA
• DNA Polymerase enzyme responsible for addition of
nucleotides
• A binds T (2 H-bonds)
• G binds C (3 H-bonds)
DNA
Replication
Replication Example
• TACAGTCCATTCACCTAGGATATT
Ribonucleic Acid
• RNA is also
composed of
nucleotides
• Ribose sugar
• Phosphate group
• Bases
• A, Uracil (U)
• C, G
RNA STRUCTURE
• RNA is single
stranded
• An RNA copy of DNA
is made during
Transcription
Comparison of DNA & RNA
DNA
Sugar
Bases
# of Strands
RNA
Types of RNA
Messenger RNA, mRNA

Carries code (message) for
protein to be synthesized
• Transfer RNA, tRNA

Carries appropriate
amino acid to
ribosome to be
incorporated into
protein
Ribosomal RNA, rRNA

The RNA component of the
ribosome (recall that a ribosome is
composed of RNA plus protein)
Transcription
• Occurs in the nucleus
• Make a messenger RNA copy of the DNA
(gene)
• RNA Polymerase enzyme copies the DNA
• Base Pairing
• DNA
•A
•T
•C
•G
RNA
U
A
G
C
Transcription
• **Only transcribe a gene when it is needed
• All cells have the same genes but have differential
expression of those genes
Transcription
• Transcribe the following DNA sequence:
• TACAGTCCATTCACCTAGGATATT
Following transcription, the
mRNA leaves the nucleus and
enters the cytosol where it is
threaded through a ribosome to
undergo translation.
Translation
• mRNA is translated into protein
• Occurs on the ribosome
• mRNA is read 3 bases at a time
• These are called codons
• Each codon corresponds to an amino acid
The Genetic Code
• There are 64 codons that make up the genetic
code
• Each codon corresponds to an amino acid
• 20 amino acids in nature
• Code is redundant
• 1 START codon: AUG
• 3 STOP codons: UAA, UAG, UGA
• Amino acids are attached to a specific tRNA
• tRNA carries the amino acid to the growing
polypeptide chain
Genetic Code
Translation
• 1st codon of every gene is always AUG
• START codon
• Translation begins at AUG
• Translation ends when a STOP codon is
reached
• UAA, UAG, UGA
• Remember, Amino acids are attached to a
specific tRNA
• Has anticodon sequence
• If mRNA is UAA, tRNA anticodon is AUU
Translate the mRNA sequence from
before
Translation
• Each time a codon is read, a new amino acid is added
to a growing chain
• Peptide bonds form between each amino acid
• When a STOP codon is reached, the protein is
released
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1
1
Fig. 4.24
2
Growing
The transfer RNA molecule
polypeptide
for the last amino acid added
chain
holds the growing polypeptide
Anticodon
chain and is attached to its
complementary codon on mRNA. A U G G G C U
1
2
3
4
Next amino acid
5
6
Transfer
RNA
U G C C G U
C C G C A A C G G C A G G C A A G C G U
3
4
5
6
Messenger
RNA
7
Codons
Peptide bond
1
2
2
Growing
polypeptide
chain
3
A second tRNA binds
complementarily to the
next codon, and in doing
Anticodon
so brings the next amino
acid into position on the ribosome.
A U G G G C U C
A peptide bond forms, linking
the new amino acid to the
growing polypeptide chain.
1
2
3
4
Next amino acid
5
6
Transfer
RNA
U G C C G U
C G C A A C G G C A G G C A A G C G U
4
5
6
Messenger
RNA
7
Codons
1
2
3 The tRNA molecule that
brought the last amino acid
to the ribosome is released
to the cytoplasm, and will be
used again. The ribosome
moves to a new position at
the next codon on mRNA.
3
4
5
7
Next
amino acid
6
Transfer
RNA
C G U
A U G G G C U C C G C A A C G G C A G G C A A G C G U
1
2
3
4
5
6
7
Messenger
RNA
Ribosome
1
2
4 A new tRNA complementary to
3
4
5
6
the next codon on mRNA brings
the next amino acid to be added
to the growing polypeptide chain.
7
Next
amino acid
Transfer
RNA
C G U C C G
A U G G G C U C C G C A A C G G C A G G C A A G C G U
1
2
3
4
5
6
7
Messenger
RNA
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cytoplasm
DNA
double
helix
T
T
G
T
C
T
G
A
C
A
T
A
C
A
G
C
A
DNA
strands
pulled
apart
T
A
T
T
U
A
G
G
G
C
G
G
C
G
C
C
C
C
T
G
T
C
A
A
C
G
T
G
C
G
G
C
A
A
C
T
C
T
G
G
T
T
A
T
C
C
G
C
C
G
C
C
G
A
G
A
T
G
C
G
A
C
A
A
G
A
G
C
A
T
G
G
C
C
C
C
C
G
A
C
T
C
T
G
C
A
A
T
U
G
G
A
A
A
C
C
G
C
T
A
C
T
G
1 DNA
information
is copied, or
transcribed,
into mRNA
following
complementary
base pairing
moves along the
mRNA, more amino
acids are added
Messenger
C
G
RNA
A
G
4 As the ribosome
G
G
T
G
A
G
Nuclear
pore
G
C
U
T
the ribosome releases
the new protein
G
C
C
G
5 At the end of the mRNA
G
U
C
C
A
G
Amino acids
recognize complementary mRNA codons,
attached to tRNA
thus bringing the correct amino acids into
position on the growing polypeptide chain
6 tRNA molecules
Polypeptide
2 mRNA leaves
can pick up anoth
the nucleus chain
molecule of the
Messenger and attaches
same amino acid
RNA
to a ribosome
and be reused
Nucleus
A
G
3 Translation begins as tRNA anticodons
C
Transcription
(in nucleus)
C
G
T
C
A
G
G
C
C
DNA
strand
Translation
(in cytoplasm)
G
C
U
A
G
C
Direction of reading
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
Mutations
• Result from an error in DNA sequence
• Caused by many things:
• Chemicals, error in replication, sunlight, X-rays
• Mutations affect the protein product of a gene
• Not made
• Made, but wrong conformation
• Non-functional
• Protein Made in excess
Mutations Affect Protein Product
• Sickle-cell anemia
• Results from a single amino acid change in the gene that codes
for hemoglobin
• This defect causes RBCs to become sickle-shaped in low oxygen
situations
Mutations Affect Protein Product
• Non-functional protein
• Hemoglobin in Sickle Cell Trait/Anemia
• CFTR pump in Cystic Fibrosis
Wild-type hemoglobin DNA
3
Mutant hemoglobin DNA
5
C T
T
In the DNA, the
mutant template
strand has an A where
the wild-type template
has a T.
G U A
The mutant mRNA has
a U instead of an A in
one codon.
3
5
T
C A
mRNA
mRNA
G A
A
5
3
5
3
Normal hemoglobin
Sickle-cell hemoglobin
Glu
Val
The mutant (sickle-cell)
hemoglobin has a valine
(Val) instead of a glutamic
acid (Glu).
Light Micrograph – Sickle Cell Anemia
RBC’s