TOPIC 2 Cellular Level of Organization
TOPIC 2 Cellular Level of Organization
CELL PHYSIOLOGY 1
7
TRANSMISSION ELECTRON MICROSCOPE
(Internal ultrastructure)
8
An Overview of Cell Structure
• 3 Major cell subdivisions
– Plasma membrane: bounds the cell
– Nucleus: contains DNA
• Important concepts: human genome
– Cytoplasm: consists of various organelles, the cytoskeleton, and
the cytosol
• Cytoplasm is the portion of the cell interior not occupied by the
nucleus.
• Cytosol is a gel-liquid within which the organelle and
cytoskeleton are suspended.
• Organelle are discrete, well-organized structures that carry out
specialized functions.
• Cytoskeleton is protein that extends throughout the cell and
serves as the cell’s bones and muscle.
Major Constituents of Cell
CELL
Hydrophilic Water
heads
Amphipathic
Hydrophobic
tails
Water
Membrane Carbohydrate
◼ They are components of complex molecules such as proteoglycans,
glycolipids and glycoproteins.
◼ Forming a layer known as glycocalyx.
◼ Important functions of glycocalyx:
i) Lubrication and protection
-form a viscous layer that
lubricates and protects
the CM.
ii) Anchoring and locomotion
-can help anchor the cell in place because the components are sticky.
-it also participates in the locomotion of specialized cells.
iii) Specificity binding
-GP and GL can function as receptors, binding specific extracellular
compounds, such binding can alter the properties of the cell surface
and indirectly affect the cell’s behavior.
iv) Recognition
-GP and GL are recognize as normal and abnormal by cells involved
with the immune response.
Membrane Proteins
▪ A membrane is a mosaic of different protein embedded and
dispersed in the phospholipid bilayer.
▪ These protein vary in both structure and function and occur in two
spatial arrangements
❖ Membrane proteins
– 2% of the molecules in plasma membrane
– Membrane proteins are inserted within or
attached to the lipid bilayer
❖ Transmembrane proteins (integral)
– pass completely through membrane
– most are glycoproteins
❖ Peripheral proteins
- adhere to membrane surface anchored to
cytoskeleton
Membrane Protein Function
Transport, Enzymatic activity, Signal
transduction, cell-cell recognition, intercellular
joining, attachment to the cyctoskeleton and
extracellular matrix (ECM)
Signaling molecule
Receptor
Enzymes
Membrane
Protein ATP
Signal transduction
Functions (a) Transport (b) Enzymatic activity (c) Signal transduction
Glyco-
protein
Cytosol + organelles
Cytosol (ICF) vs Extracellular Fluid (ECF)
Microvilli
Golgi apparatus
Peroxisome
▪Microfilament,
▪Microtubules
▪Intermediate
filament
7 nm 8−12 nm
Tubulin dimer
Microtubule
◼ Cilia move fluid along the cell surface ◼ Flagella move cells through the
medium
-relatively stiff during the effective power
stroke & flexible during recovery stroke. ◼ Sperm cells have flagella to swim
▪ Cilia are essential to the movement of the toward the egg for fertilization
egg through the fallopian tube. process.
Microtubule
Microfilament
◼ Responsible for protein synthesis
Ribosome
◼ Ribosomes have two major subunits, that are
normally separate, distinct and made of both
RNA and proteins (both contain special
proteins and ribosomal RNA).
-Small ribosomal subunit
-Large ribosomal subunit
◼ Before protein synthesis can begin, a small
and large subunit must join together to form
complete functional ribosome.
◼ 2 types of functional ribosomes:
i) Free ribosomes make proteins used in the
cytosol
ii) Attached/fixed ribosomes make proteins
used in membranes and for export
(attached to ER).
Nucleus
▪ Largest organelle
▪ The nucleus is the largest organelle contains most of the
cell’s genes. control the activities of cell.
▪ Nuclear envelope : two unit membrane held together at
nuclear pores
▪ Nucleoplasm
▪ Chromatin (thread like structure of DNA)
▪ Nucleolus: place ribosome produced
Endoplasmic Reticulum (RER,SER)
◼ ER is a network of intracellular
membranes connected to the nuclear
envelope (surrounds the nucleus).
(Endo=within, plasm=cytoplasm,
reticulum=network).
◼ The ER has 4 major functions:
i) Synthesis – proteins, carbohydrates,
lipids.
ii) Storage – storage synthesize
materials without affecting
cellular operations.
iii) Transport – materials can travel in
the ER.
iv) Detoxification – drugs or toxins
can be absorbed
and then neutralized by the
enzymes within it.
Rough
Endoplasmic
Reticulum
(RER)
➢ Smooth refer to the fact that no ribosomes are associated with the ER.
➢ Associated with the synthesis of lipids and carbohydrates
➢ The SER functions:
➢ Synthesis of phospholipids and cholesterol needed for maintenance and
growth of the cell membrane, nuclear membrane, and Golgi apparatus in cells.
➢ Synthesis of steroid hormone such as androgens and estrogens.
➢ Synthesis and storage of glycerides especially triacylglycerides, in liver and
fat cells.
➢ Synthesis and storage of glycogen in skeletal muscle and liver cells.
➢ Responsible for the detoxification and inactivation of drugs especially in liver
and kidneys cells.
Golgi Apparatus
▪ The Golgi apparatus consists of cis face
(“receiving” side of
flattened membranous sacs called Golgi apparatus)
cisternae. Cisternae
▪ Synthesizes carbohydrate,
modification and packaging of protein
and lipids.
▪ Sorts and packages materials into
transport vesicles. 3 types of vesicles
▪ some become lysosomes
(packages special enzymes within
vesicles for use in the cytosol)
▪ some become secretory vesicles
(such as hormones and enzymes,
trans face
for release through exocytosis) (“shipping” side of
▪ some fuse with plasma membrane Golgi apparatus)
(renews or modifies the cell
membrane)
The GA-Processing and Packaging of Proteins
Rough ER
Smooth ER
Plasma
membrane
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Nucleus
Rough ER
Smooth ER
cis Golgi
Plasma
membrane
trans Golgi
50
Nucleus
Rough ER
Smooth ER
cis Golgi
Plasma
membrane
trans Golgi
51
Lysosomes
▪ A lysosome is a membranous sac of hydrolytic enzymes that can
digest macromolecules (proteins, fats, polysaccharides, and
nucleic acids)
▪ Lysosomal enzymes function
1. Digest food (food enter to cell by phagocytosis)
2. Destroy bacteria
3. Autophagy (digest unwanted organelle)
4. Breakdown stored glycogen in liver to release glucose
3. Programmed cell
destruction (autolysis)
• Destruction of cells by
their own lysosomes is
important during
metamorphosis and
development.
➢ Degradation of tadpole
tail of frog and the
tissues webbed
between the human
embryo’s finger .
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Peroxisomes
▪ Resemble lysosomes but contain different enzymes
▪ In all cells but abundant in liver and kidney
▪ contain oxidative enzymes important in
metabolism.
▪ Functions
▪ Detoxificationof alcohol, other drugs and toxins.
▪ Neutralize free radicals - Protect the cell from the
potentially damaging effects of free radicals
produced during catabolism.
▪ Breakdown of fats into smaller molecules (acetyl
coA). The product carried to the mitochondria as
fuel for cellular respiration.
LYSOSOME & PEROXISOMES
Mitochondria
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Transport Material Across Cell Membrane
Plasma membrane - Selective Semipermeable Membrane
WATER
Sugar
molecule
H2O
Selectively
permeable
membrane
B. Osmosis
Osmosis
Passive Mechanism:
C. Filtration
• Movement of particles
through a selectively
permeable membrane
by hydrostatic pressure
• Examples
– filtration of nutrients
from blood capillaries
into tissue fluids
– filtration of wastes from
the blood in the kidneys
Passive Mechanism:
D. Facilitated Diffusion
• Transport of solute across membrane down its
concentration gradient
• No ATP used
• Solute binds to carrier, it changes shape then releases
solute on other side of membrane
Diffusion in plasma membrane
◼ Non-polar molecules move via simple diffusion
◼ Many ions cross membranes through ion channels
◼ Polar molecules are transported by carrier-mediated
facilitated diffusion
Active mechanism: Active Transport
▪ Transport of solute across membrane up (against) its
concentration gradient.
◼ Energy is required to drive all active processes
Na+ Na+
Na+
K+
K+
K+
K+
K+
P
6 K+ 5 4 Pi
Secondary Active Transport
◼ Secondary active transport also moves ions or molecules “uphill”
(against their concentration gradients)
◼ Energy from an existing ion gradient powers this process
◼ Symporters and antiporters are two types of secondary active
transport - many specific examples of each type exist in cells
Transport in Vesicles
EXTRACELLULAR
FLUID
Solutes
Pseudopodium Receptor
Plasma Ligand
membrane
Coat proteins
Coated
“Food” or pit
other particle
Coated
vesicle
Vesicle
Food
vacuole
CYTOPLASM
ENDOCYTOSIS
Phagocytosis or “Cell-Eating”
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Essential Elements of life
➢ Elements: substances cannot be
broken down into simpler
substances. (simplest form of
matter to have unique chemical
properties).
➢ Essential elements
➢ Include carbon, hydrogen, oxygen
and nitrogen
➢ Make up 96% of human mass
➢ A few other elements
➢ Calcium, phosphorus, potassium,
sulfur, sodium, chlorine,
magnesium
➢ Make up the remaining 3.8% of
living matter
87
Essential Elements of life
➢ Trace element
❖ Are required by an organism in only minute
quantities. 14 trace elements; 1%
❖ Some trace elements, like iron (Fe), are required
by all organisms.
❖ Other trace elements are required only by some
species.
❖ For example, a daily intake
of 0.15 milligrams of iodine
is required for normal
activity of the human
thyroid gland.
89
ATOM
• Units of chemical elements are
called atoms.
• Atom
➢Consists of a nucleus (protons
and neutrons) and electrons CARBON ATOM
96
Chemical Bonds
• Chemical bonds – forces that hold molecules together,
or attract one molecule to another
Second shell
98
Covalent Bonds
• A covalent bond is the sharing of a pair of
valence electrons by two atoms.
– If two atoms come close enough that their
unshared orbitals overlap, each atom can count
both electrons toward its goal of filling the valence
shell.
– For example, if two hydrogen atoms come close
enough that their 1s orbitals overlap, then they can
share the single electrons that each contributes.
99
• Share pair of electrons and form hydrogen molecules,
each contributing one electron to the shared pair.
• Both hydrogen atoms acquire completely filled outer
shell 2 (electron) and become stable.
• Oxygen needs to add 2 electrons to the 6
already present to complete its valence shell.
– Two oxygen atoms can form a molecule by
sharing two pairs of valence electrons.
– These atoms have formed a double covalent
bond.
101
Single Covalent Bond
- sharing of one pair of valence electrons
103
Covalent Bonding in Compound
Name and Electron Lewis Dot Space-
Molecular Distribution Structure and Filling
Formula Diagram Structural Model
Formula
104
Ionic Bonds
• In some cases, atom strip electrons away from
their bonding partners.
• Electron transfer between two atoms creates
ions.
• Ions
➢ Are atom with more or fewer electrons than usual
➢ Are charged atom
• An anion is negatively charged ions.
• A cation is positively charged.
• An ionic bond is an attraction between anions and
cations . 105
• An example is the transfer of an electron from
sodium to chlorine
– sodium with one valence electron in its third shell
transfers this electron to chlorine with 7 valence
electrons in its third shell.
– Now, sodium has a full valence shell (the second)
and chlorine has a full valence shell (the third).
106
• After the transfer, both atoms are no longer
neutral, but have charges and are called ions.
• Sodium has one more proton than electrons
and has a net positive charge.
– Atoms with positive charges are cations.
• Chlorine has one more electron than protons
and has a net negative charge.
– Atoms with negative charges are anions.
Ionic bond
attraction
between anions
and cations .
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Hydrogen Bonds
• Hydrogen bond – a weak attraction
between a slightly positive hydrogen atom
in one molecule and a slightly negative
oxygen or nitrogen atom in another.
➢ Example molecules of water are
weakly attracted to each other by
hydrogen bonds
❖ Play a critical role in the structure and
function of proteins and nucleic acids
Protein
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Chemical Reaction
▪ Chemical reaction – a process in which a
covalent or ionic bond is formed or
broken.
▪ Classes of chemical reactions
➢ decomposition reactions
➢ synthesis reactions
➢ exchange reactions
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Decomposition
Reactions
• AB → A + B
Glucose molecules
(a) Decomposition reaction
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Synthesis Reactions
• A + B → AB
Protein molecule
and sodium
bicarbonate C A
(NaHCO3) from the D B
pancreas combine
to form NaCl and AC C A
H2CO3. +
BD D B
–simple sugars
O
H H
H
OH H OH
HO
H OH
OH H
H OH
fructose H OH
Fructose
complex carbohydrates H
H HO
CH2OH
OH H
Disaccharides
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
OH H H HO
O
HO CH2OH
H OH OH H
• glucose + fructose
OH H H
H H H H
O
Maltose
• glucose + glucose H OH H OH
1–4
glycosidic
1 linkage 4
1–2
glycosidic
1 linkage 2
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Polysaccharides
• Long chains of glucose
• 3 polysaccharides of interest in humans
– Glycogen: energy storage polysaccharide in animals
• made by cells of liver, muscles, brain, uterus, and vagina
• liver makes glycogen after a meal when glucose level is high, then
breaks it down later to maintain blood glucose levels
Amylose
(a) Starch: 1 m
a plant polysaccharide
Glycogen
(b) Glycogen: 0.5 m
an animal polysaccharide 121
Organic Molecules: Lipids
• Hydrophobic organic molecule
–composed of carbon, hydrogen and
oxygen
• Five primary types in humans
–fatty acids
–triglycerides
–phospholipids
–eicosanoids
–steroids
Fatty Acids
• Types
– saturated - carbon atoms saturated with hydrogen
– unsaturated - contains C=C bonds without hydrogen
– polyunsaturated – contains many C=C bonds
– essential fatty acids – obtained from diet, body can
not synthesize
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
H H H H H H H H H H H H H H H
O
C C C C C C C C C C C C C C C C H
HO
H H H H H H H H H H H H H H H
Palmitic acid (saturated)
CH3(CH2)14COOH
Triglycerides (Neutral Fats)
• 3 fatty acids covalently bonded to glycerol molecule
Fatty acid
(in this case, palmitic acid)
Ester linkage
Triacylglycerol
(FAT)
- 3 molecule of
fatty acid and 1
molecule of
glycerol
Structural
formula of a
saturated fat
molecule
Structural
formula of an
unsaturated fat
molecule
Space-filling
model of stearic
acid, a saturated
fatty acid Space-filling model
of oleic acid, an
unsaturated fatty
acid
Cis double bond
causes bending.
Phospholipids
• similar to neutral fat CH3
CH2
group
(choline)
group O
–O P O
Phosphate Hydrophilic
group region (head)
• structural foundation O
Glycerol
CH2 CH CH2
of cell membrane O O
O C C O
hydrophilic
(b)
Choline Amphiphatic
molecule:
Hydrophilic head
Phosphate 1. Hydrophilic
(water-soluble) part
Glycerol
-Called Head
2. Hydrophobic
(water repelling)
- Called Tail
Hydrophobic tails
Fatty acids
Hydrophilic
head
Hydrophobic
tails
Amino
• protein - a polymer of acids
amino acids
– most useful Amino end
Carboxyl end
Protein Structure and Shape
Primary structure
Amino
acids
Carboxyl end
Primary structure
Protein Structure and Shape
Secondary structure Secondary structure
coiled or folded
shape held together
by hydrogen bonds helix
Hydrogen bond
pleated sheet
strand, shown as a flat
arrow pointing toward
the carboxyl end
Hydrogen bond
Secondary structure
Protein Structure and Shape
Tertiary structure
– further bending and folding of proteins into globular and
fibrous shapes
• globular proteins –compact structure good for
proteins embedded in cell membrane or that move
about in fluid
• fibrous proteins – slender filaments better suited for
roles as in muscle contraction and strengthening skin
Tertiary structure
Protein Structure and Shape
Quaternary structure Heme
• associations of two or more
Iron
separate polypeptide
chains subunit
• Functional protein
subunit
subunit
subunit
(Four polypeptides)
Hemoglobin
Quaternary structure
Protein Conformation and Denaturation
Conformation – unique three dimensional shape of protein
crucial to function
– some proteins can reversibly change their conformation
(renaturation)
• enzyme function
• muscle contraction
• opening and closing of cell membrane pores
Denaturation
• extreme conformational
change that destroys
function
• extreme heat or pH
Protein Functions
Enzymatic proteins Defensive proteins
Function: Selective acceleration of chemical reactions Function: Protection against disease
Example: Digestive enzymes catalyze the hydrolysis Example: Antibodies inactivate and help destroy
of bonds in food molecules. viruses and bacteria.
Enzyme
Antibodies
Virus Bacterium
Receptor
Signaling protein
Insulin
High secreted Normal molecules
blood sugar blood sugar
Actin Myosin
Collagen
❖ In 1953, James Watson and Francis Crick introduced an elegant double-helical model
for the structure of deoxyribonucleic acid, or DNA.
❖ Hereditary information is encoded in DNA and reproduced in all cells of the body.
142
DNA Double Helix
Deoxyribonucleic acid (DNA)—a long, threadlike molecule with
uniform diameter, but varied length.
G
5 end
C
C G Hydrogen bond
3 end
G C
G C T A
3.4 nm
T A
G C G C
C G
A T
1 nm C G
T A
C G
G C
C G A T
A T 3 end
A T
0.34 nm
T A 5 end
3C
Nucleoside
Nitrogenous
base Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA)
5C Purines
1C
Phosphate 3C
group Sugar
5C
(pentose)
Adenine (A) Guanine (G)
3C (b) Nucleotide
Sugars
3 end
(a) Polynucleotide, or nucleic acid
145
1. Sugar
In DNA, the sugar
is Deoxyribose;
in RNA, the sugar
is Ribose.
2. Phosphate
146
3. Nitrogenous base
• Pyrimidines
- single carbon-nitrogen ring
– uracil - RNA only
– thymine - DNA only
• Purines
- double carbon-nitrogen ring
▪ DNA bases—ATCG
▪ RNA - AUCG
147
• DNA is made up of:
– Four nucleotides: Adenine,
Thymine, Guanine and
Cytosine
– These follow the rules of
base-pairing:
• Adenine bonds with Thymine
( 2-hydrogen bond)
• Guanine bonds with Cytosine
(3-hydrogen bond)
– A sugar-phosphate backbone
• DNA is arranged in an
double-helix
148
DNA VS RNA
• There are two types of nucleic acids
(polynucletiode)
– DNA (deoxyribonucleic acid) and RNA
(ribonucleic acid).
• RNA much smaller cousin of DNA (fewer
bases)
– Messenger RNA (mRNA) over 10,000 bases
– Ribosomal RNA (rRNA)
– Transfer RNA (tRNA) 70 to 90 bases
• DNA averages 100 million base pairs
DNA RNA
Double stranded Single stranded
3 forms RNA
1 forms DNA 1. rRNA
2. mRNA
3. tRNA
DNA can only be found in cell ‘s nucleus RNA could be found in nucleus and
cytoplasm.
3 type of RNA (1 strand polynucleotide)
1. mRNA – Messenger RNA
- Linear single polynucleotide
- Carries the genetic code transcripted from DNA in the nucleus to the
ribosome in the cytoplasm for protein synthesis
2. rRNA – Ribosomal RNA
- Synthesize in nucleolus. Contain RNA + Protein
- Contain large (50s) and small subunit (30s) – combines form ribosomes
- Organelle involve in translate mRNA to polypeptide.
3. tRNA – Transfer RNA
- Single stranded polynucleotide folded into clover – leaf shape
- Bring amino acid to ribosome during translation.
- Have 2 sides
➢ 1 side of tRNA molecule attaches to amino acids
➢Other has anticodon that complementary to codon on mRNA 151
mRNA – linear
polynucleotide
152
rRNA - ribosome
E P A
tRNA
154
What Is a Gene?
157
Protein Synthesis
Process of protein synthesis
DNA mRNA Protein
DNA Transcription
TRANSCRIPTION ▪ DNA too large to leave nucleus and
participate
Pre-mRNA ▪ Transcription—copying genetic
RNA PROCESSING instructions from DNA to mRNA
mRNA
Translation
▪ Process that converts the language of
nucleotides into the language of
TRANSLATION amino acids
Ribosome ▪ Ribosomes—translate sequence of
nucleotides into the sequence of
Polypeptide amino acids
▪ Occur mainly in cytosol, on surface of
rough ER and nuclear envelope
Protein synthesis
Protein Processing and Secretion
160
161
TOPIC 2: Cellular Level Organization
CELL PHYSIOLOGY III
Cell Division & Cell Cycle
165
166
There are two type of cell division
1. MITOSIS
- Division of cells that produce 2 daughter
cell which genetically identical to the
mother cell
2. MEIOSIS
- Division of cells that produce 4 daughter
cell and the genetic content is different
than mother cell
167
MITOSIS
- Division cell produce 2 daughter cell
- Daughter cell genetically identical to the mother cell
- Chromosome number daughter cell same with
mother cell
- Important of mitosis
➢ Increase the number of cell for growth
➢ Repair and replace the damage or dead cell
➢ Produce daughter cell which genetically identical
to mother cell
➢ The basis of asexual reproduction of unicellular
organisms.
168
Chromosomal
OVERVIEW OF MITOSIS Chromosomes DNA molecules
169
MEIOSIS
• Meiosis reduces the number of parental
chromosome sets from diploid (2n) to haploid (n)
• Meiosis occurs in the reproductive cells
➢ Plant (pollen and eggs)
➢ Animal (sperm and ovum)
• Meiosis produce
➢ 4 daughter cell which contain haploid (n)
number of chromosome of mother cell
diploid (2n)
➢ Genetic content is different than mother cell
172
5 µm
Pair of homologous
replicated chromosomes
Centromere
Sister
chromatids
Metaphase
chromosome
Homologous chromosomes – the two
chromosomes composing a pair have the same
length, centromere position and both carry
genes controlling the same inherited
characters.
Key
Maternal set of
chromosomes (n = 3)
2n = 6
Paternal set of
chromosomes (n = 3)
▪ Metaphase I ▪ Metaphase II
▪ Anaphase I ▪ Anaphase II
176
Meiosis reduces
chromosome number by
copying the chromosomes
once, but dividing twice.
During another round of cell division, the sister chromatids finally separate;
Cleavage four haploid daughter cells result, containing unduplicated chromosomes.
furrow
Homologous Sister chromatids Haploid daughter
Homologous Fragments chromosomes separate cells forming
chromosomes of nuclear separate
envelope
Microtubule Each pair of homologous Two haploid cells
attached to chromosomes separates. form; each chromosome
kinetochore still consists of two
Chromosomes line up sister chromatids.
Duplicated homologous
chromosomes (red and blue) by homologous pairs.
pair and exchange segments;
2n = 6 in this example.
178
THE FIRST MEIOTIC DIVISION
Cleavage
furrow
Homologous
Homologous Fragments chromosomes
chromosomes of nuclear separate
envelope
Microtubule Each pair of homologous Two haploid
attached to chromosomes separates. cells form; each
kinetochore chromosome
Duplicated homologous Chromosomes line up still consists
chromosomes (red and blue) by homologous pairs. of two sister
pair and exchange segments; chromatids.
2n = 6 in this example.
179
THE SECOND MEIOTIC DIVISION
Telophase II and
Prophase II Metaphase II Anaphase II
Cytokinesis
During another round of cell division, the sister chromatids finally separate;
four haploid daughter cells result, containing unduplicated chromosomes.
Sister chromatids Haploid daughter
separate cells forming
180