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Chapter 2

Molecules, Cells
and Theories
Molecules, Cells and Theories
Overview
Biomolecules

The Cell

Theories of Aging




Cells contain an aqueous solution,
with 1000s of solutes:
single atoms (electrolytes)
small molecules
large molecules
SUPER KEY CONCEPT

Water
Composition of Tissue (by weight)
FOUR Major Classes of
Biomolecules?
FOUR Major Classes of
Biomolecules
proteins
carbohydrates
lipids
nucleic acids
MOST responsible for LIFE?
Water
Life by Purves, 7th Ed. Figure 3.2
Composition of Tissue (by weight)
Water
Life by Purves, 7th Ed. Figure 3.2
Composition of Tissue (by weight)
SIX basic nutrients?
Water
Life by Purves, 7th Ed. Figure 3.2
Composition of Tissue (by weight)
HOW do large biomolecules
get to BE so large?
Large biomolecules are
polymers (molecular chains).

KEY CONCEPT
You ARE what you eat, but
food monomers new polymers
hydrolysis

DIGESTION ANABOLISM
(within gut) (within cells)

You ARE what you eat, but
There are TWO TYPES of
metabolism in the cell:
anabolism
? ? ?

catabolism ? anabolism
KEY CONCEPT
CHON
Biomolecules Primarily Consist
of FOUR Different Atoms
FOUR Major Classes of
Biomolecules
proteins
carbohydrates
lipids
nucleic acids
1. Structural Proteins: form structural
components of the cell.


2. Enzymes: speed and regulate
biochemistry.


Two Main Types
KEY CONCEPT
The 3D shape of proteins is
ESSENTIAL for their function

it allows it to INTERACT with a
specific molecule.

A Polypeptide

What causes a protein to fold?

Folding occurs SPONTANEOUSLY,
based on the amino acid sequence.

Environmental factors also affect the
conformation.

Key Concept
Folding occurs SPONTANEOUSLY,
based on the amino acid sequence.

Environmental factors also affect the
conformation.
pH
[salt]
Temperature

Key Concept
Proteins Have FOUR Levels
of Structure

Protein Conformation

Making proteins is ANABOLIC.


Where does the ENERGY
come from???
FOUR Major Classes of
Biomolecules
proteins
carbohydrates
lipids
nucleic acids
Carbohydrates
sugars and sugar polymers

monosaccharides
polysaccharides

FUNCTIONS: energy AND
structure


Glucose

Polysaccharides
FOUR Major Classes of
Biomolecules
proteins
carbohydrates
lipids
nucleic acids
Lipids

molecules that are mostly H and C

Functions:
1) energy source (fats)
2) structural (phospholipids)
3) cholesterol and its derivatives
Triglyceride

Saturated?

Unsaturated?

Phospholipid

Hydrophilic AND Hydrophobic
Fig 5.13
Cholesterol

Nucleic Acids
nucleotides
4 different ones
polynucleotide

two types

Functions:
information storage (polynucleotides)

Nucleic Acids
nucleotides
4 different ones
polynucleotide

two types

Functions:
information storage (polynucleotides)
energy source (a nucleotide)
Nucleic Acids
nucleotides
4 different ones
polynucleotide

two types

Functions:
information storage (polynucleotides)
energy source (a nucleotide: ATP)
ATP



DNA RNA protein
WHY?
DNA RNA protein
WHY?
How many X genes do we have??
The Central Dogma
transcription translation
a gene mRNA polypeptide
DNA RNA protein
replication
RECAP
1. Cells are constructed for FOUR main
types of biomolecules.
2. The most complex are proteins, which
provide both structure and function.
3. Genes (DNA) provide the instructions
to make all proteins.
The Central Dogma
a gene mRNA polypeptide
DNA RNA protein
replication
The DNA is Organized
It is not just one long strand!

It is organized into distinct units
called CHROMOSOMES.

How are the TERMS related?

Chromatin (size = large)

All genetic material in the nucleus

3 x 10
9
base pairs

The DNA from ONE cell stretched out would
be about 6 feet long.

RELATIONSHIPS
RELATIONSHIPS

CHROMOSOME (size = medium)
DNA/PROTEIN structures carrying GENES
1 x 10
6-7
nucleotides per chromosome
23 PAIRS in humans
The essential
GENOME

no pairs!

GENE (size = small)
nucleotide sequence of DNA that controls ONE
hereditary characteristic of an organism.

encodes an RNA molecule (Ex: mRNA)

~ 1 x 10
4
5 x 10
5
bp per gene
ATATGCATGCAGA
TATACGTACGTCT
CHROMOSOME
GENE
CHROMATIN
RELATIONSHIPS

Heterochromatin
Tightly PACKED chromatin, not
available for gene expression.
Molecules, Cells and Theories
Overview
Biomolecules

The Cell

Theories of Aging



Cell Membrane
A barrier to maintain the cells internal
chemistry.

Made up of:
1) phospholipids
2) diverse proteins

Also provides broad FUNCTIONALITY:
Ex: transport, receptors, joining cells

Cell Membrane
Mitochondria
Use sugar, fat and protein to
make ATP.


Once an ancient BACTERIAL CELL!


Origin of Mitochondria?
Once an ancient BACTERIAL CELL!


Have their own DNA!
Origin of Mitochondria?
Allow for the MANUFACTURE and
SECRETION of biomolecules.
ER and Golgi
Lysosome
Life by Purves, et.al., 7th Ed. Figure 7.13
Gives SHAPE/SUPPORT as well as
additional functionality to the cell.
Cytoskeleton
Cytoskeleton
Our Multicellularity
= ?

1. Cells + other structure.

2. Also: empty space!

Multicellularity
Intercellular Materials
1. Amorphous Materials: vary in their
water/protein content
Ex: blood
Ex: cartilage
Ex: bone

2. Fibers
a) Collagen: fibers twisted into thick cables
Ex: tendons, ligaments, bone
b) Elastin: more flexible
Ex: dermis skin, ears

WHY do cells divide?
1) Growth/development

2) Repair/regeneration

3) Reproduction

Cells Reproduce by Mitosis
1. Chromosomes are duplicated by DNA
replication.

2. Pulled apart by the cytoskeleton,
which also pinches cell in half.


Cell Cycle
Do ALL cells divide?


The frequency of mitosis
depends on cell type.
G
0
1) Continuous

2) Based on need

3) Rare/never

G
o
applies to 2 and 3
Most human cells are in G
o
Frequency of Mitosis Depends
on Cell Type
Replicating a chromosomes ENDS
(telomeres) requires a special enzyme:

Telomerase

Without this enzyme, a cells ability to
proliferate is limited!
Key Concept
The cells of humans and other
animals CANNOT DIVIDE
INDEFINITELY in culture.
The # of rounds of cell division
characteristic of that cell type is the
Hayflick Limit.
It decreases as an organism ages!
Key Concept
Molecules, Cells and Theories
Overview
Biomolecules

The Cell

Theories of Aging


Numerous theories have been
proposed to explain biological aging.

= hypotheses

overlap
aging may involve several/all/(none?)
Key Concept
Why consider aging from an
evolutionary standpoint?

Nothing in biology makes sense
except in the light of evolution.


-- 1973 Essay by Theodosius Dobzhansky

Evolution
The change in the genetic composition
of a population from generation to
generation, that over time brings about
new species.

Occurs by mutation.

Proceeds by natural selection.
survival of the fittest
= reproductive success!
Why isnt aging ELIMINATED
by evolution?
An organism is no longer needed
following successful reproduction!

= selfish gene theory (Dawson)

Limited resources may have resulted
in a BALANCE b/w the genes for
SURVIVAL (defense/repair) and genes
for REPRODUCTION.
1) The changes addressed must
occur COMMONLY in all members
of the species.
2) The process must be
PROGRESSIVE.
3) The process must lead to ORGAN
DYSFUNCTIONS that ultimately
lead to failure of organ/system.

Three Criteria for Valid Theory
1) Aging results from WEARING OUT
of an organ/system.
2) Aging results from nonreversible
CHEMICAL CHANGES within cells
that alter its functioning.
3) Aging is programmed by a
BIOLOGICAL CLOCK, located in a
single center or in each cell.

Three Main Groups of Theories
Theories of Aging
1. Genetic
2. Rate of Living
3. Free Radical
4. Mitochondrial
5. Clinker
6. Cross-Linkage
7. Immune Deficiency
8. Wear and Tear
Genetic Theories
1. Death Gene Theory
2. Telomere Theory
3. Somatic Mutation
4. Faulty DNA Repair
5. Error Catastrophe

Death Gene Theory

A SET OF GENES activates late in life,
and tells the body to deteriorate and
die.

Could genes involved in age-related
diseases BE the death genes?

Telomere Theory
Shortening of telomeres affects the
expression of certain genes.

Ex: through heterochromatin unwinding

May occur at DIFFERENT RATES in
different tissues!
Somatic Mutation Theory
Harmful factors may INJURE GENES.

Ex: radiation, toxic chemicals, free
radicals

Simplistic, but may be combine/
contribute to free radical and faulty DNA
repair theories.

Faulty DNA Repair Theory
DNA damage is repaired EARLY in life.


Over time, the repair mechanisms
begin to fail.

Error Catastrophe Theory
Damage to RNA and protein result in
biological aging.

EX: protein synthesis proteins, leading
to accumulation of mistakes

Disproven!


RECAP: Genetic Theories
1. Death Gene Theory
2. Telomere Theory
3. Somatic Mutation
4. Faulty DNA Repair
5. Error Catastrophe

Which involves a programmed
BIOLOGICAL CLOCK?
RECAP: Genetic Theories
1. Death Gene Theory
2. Telomere Theory
3. Somatic Mutation
4. Faulty DNA Repair
5. Error Catastrophe

Which involve(s) nonreversible
CHEMICAL CHANGES in cells?
RECAP: Genetic Theories
1. Death Gene Theory
2. Telomere Theory
3. Somatic Mutation
4. Faulty DNA Repair
5. Error Catastrophe

Which involve(s) WEARING
OUT of an organ/system?
RECAP: Genetic Theories
1. Death Gene Theory
2. Telomere Theory
3. Somatic Mutation
4. Faulty DNA Repair
5. Error Catastrophe

Which has been DISPROVEN?
RECAP: Genetic Theories
1. Death Gene Theory
2. Telomere Theory
3. Somatic Mutation
4. Faulty DNA Repair
5. Error Catastrophe

Which has been reworked
into *FR and FDR?
Theories of Aging
1. Genetic
2. Rate of Living
3. Free Radical
4. Mitochondrial
5. Clinker
6. Cross-Linkage
7. Immune Deficiency
8. Wear and Tear
Rate of Living Theory
Metabolic rate is DIRECTLY related to the
rate of aging, and INVERSELY related to
life span.

Animals can use only a FIXED AMOUNT
of calories/oxygen in their lifetime.

DISPROVEN: by comparison of different
organisms, etc. May combine/
contribute to *FR and mito *FR theories!
Free Radical
An atom/molecule with an ODD number
of e

san unpaired electron (*FR).


Ex: *O
2

, *OH

highly reactive!
occur naturally (Ex: in the presence
of oxygen, high glucosevia ROS)
implicated in more than 60 disorders
Ex: heart disease, cancer, Alz dis
damages lipids, proteins, and DNA
eliminated by antioxidants

Free Radical Theory
FREE RADICAL DAMANGE is a OR the
main reason for biological aging and
related diseases.
TO:
lipids: membrane permeability,
mitochondrial energy production,
atherosclerosis, more *FR
proteins: disrupts enzymes, structure
DNA: slows cell division, promotes
cancer
Mitochondrial Theory
Mitochondrial activity AND damage
cause aging. Ties FREE RADICAL
THEORY to mitochondria!
Ex: mitochondria are a main source of
*FRs!
Ex: *FRs damage mitochondria
Ex: Radiation/chemicals damage mito
Ex: damage accumulates over time
Ex: mito have DNA
Ex: mito DO NOT have DNA repair

Clinker Theory
Waste products accumulate in cells
over time. (Cellular garbage theory)

Simplistic, but may be combine/
contribute to C-L theory.
Ex: accumulation of misfolded
proteins.

Cross-Linkage Theory
Post-translational modification to
proteins resulting in irreversible
changes to their structure, occurring
over time. Affects flexibility/functioning/
size of tissues and body parts. Broad
effects: skin, arteries
Due to: free radicals and glucose
Glycation
Covalent joining of a sugar
(Ex: glucose) to a protein via
particular amino acids.

without an enzyme

(vs. glycosylation)

Cross-Linkage Theory
Post-translational modification to
proteins resulting in irreversible
changes to their structure, occurring
over time. Affects flexibility/functioning/
size of tissues and body parts. Broad
effects: skin, arteries
Due to: free radicals and glucose
Esp. affects diabetics!
Ex: enzymes
Ex: collagen (~ 30% of bodys proteins!)
Ex: agg of proteins leads to neurodeg disease
Immune Deficiency Theory
Over time, immune system begins to
damage YOUR tissues
(autoimmunity).
Wear and Tear Theory
An accumulation of injuries adversely
affects the tissues/bodies.
Which theory is correct?
Aging may be due to a
COMBINATION of these or still
other causes!

some more/less important?
a chain reaction
cause/effect?

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