Dr. Alvi Milliana Risma Aprinda K. UIN Maliki Malang

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dr.

Alvi Milliana
Risma Aprinda K.
UIN Maliki Malang
Discovery of the Cells
Robert Hooke was first discovered cell in 1665

 1600’s- the invention of the


microscope
 in 1665 Robert Hooke first observed
cork cells.
 It looked strangely similar to cellula
or small rooms which monks
inhabited
 Hooke actually saw the dead cell
walls of plant cell (cork tree). No
nucleus and other organelles
Cell Theory
1675: Antonie van Lieuwenhoek
first observed living cells in pond
water.

Paramecium

Diatoms
Cell Theory 1839: German biologist Theodor
Schwann stated that all animals are
made of cells.
1838: German botanist Schleiden
concluded that all plants are made of
cells.

ONION CELLS

A. Gut B. brain C. bone marrow


d. cartilage e. muscle
F. kidney
Cell Theory

 Schleiden & Schwann (1839): Organism are composed
of similar units of organization

Multicellular organism Unicellular organism


Cell Theory

1855: German physician Rudolf
Virchow concluded that all cells come
from existing cells (omnis cellula ex
cellula)

Mitosis: Cell Division


Cells

 Cells are the smallest units that can be alive
 The individual cells can grow, reproduce, process
information, respond to stimuli, and carry out an amazing
array of chemical reactions
 Every living thing is made up of one or more cells.
 Cells are the basic unit of structure and function in living
things
Formulation of the Cell Theory
1838: Theodor Schwann & Matthias Schleiden

Schwann: animal cells

Schleiden: plant cells

Conclusion
The cell retains a dual Cells form by free-cell
The cell is the unit of
existence as a distinct formation, similar to the
structure, physiology,
entity & a building block formation of crystal
and organization in
in the construction of (spontaneous
living things
organism generation)

REVISED
Robert Virchow: All cells only arise from pre-existing cells
Modern Cell Theory

All known living things are made up off cells

The cell is structural & functional unit off all living things

All cells come from pre-existing cells by division

All cells are basically the same in chemical composition


Life begin with cells

All energy flow (metabolism &


biochemistry) of life occurs within cells

Cells contain hereditary information


which is passed from cell to cell All energy flow (metabolism &
during cell division biochemistry) of life occurs within cells
Cells Change Shape & move
Cells are able to respond to stimuli

Cells growth (proliferation & enlarge) & develop (differentiation)


Cells are capable of self-regulation

xeroderma pigmentosum

correct
failure

Thymin dimer
How big are cells?
A typical animal cell is between 10 and 30 micrometers (µm).
That’s .01-.03 millimeters (mm).

How can we see cells?


By using a microscope!
In multicellular organisms, cells and
groups of cells (tissues) are organized
by their function
Specialized Cells
 Red Blood Cell
Has no nucleus so that it
can carry more oxygen
 Muscle Cells
 Long, slippery and
elastic so that they can
slide past one another
upon expansion and
contraction
 Nerve cells
 Can be several feet long
Cell Structure


1. Plasma membrane
2. Cytoplasm
3. Chromosome
4. Ribosomes
Figure 2-29 Molecular Biology of the Cell (© Garland Science 2008)
Prokaryotic Eukaryotic

Lacks of
Membrane
Membrane
bound nucleus
bound nucleus

Have no Have
membrane- membrane-
bound bound
organelles organelles

Relatively
simple Complex
internal
internal organization
organization
Cells that lack a nucleus
No membrane-bound organelles
Includes bacteria
Simplest type of cell
Single, circular chromosome
Cells that HAVE a nucleus and membrane-
bound organelles
Includes protists, fungi, plants, and animals
More complex type of cells



 Organelle= “little organ”
 Very small
 Perform various functions for a cell
 Found only inside eukaryotic cells
 Found in the cytoplasm
 May or may not be membrane-bound
 Control center of the cell
 Surrounded by a double
membrane
 Usually the easiest
organelle to see under a
microscope
 Mengendalikan seluruh kegiatan sel
 Menyimpan materi genetik dalam bentuk DNA
 menjaga integritas gen dan mengontrol ekspresi gen
 Mengatur proses metabolisme sel
 Tempat terjadinya replikasi DNA dan transkripsi
DNA
 Mengatur pembelahan sel
1. Nuclear envelope
2. Nuclear pore
3. Nucleoplasm
4. Chromosome
5. Nucleolus
 Adalah dua lapis membran
yang memisahkan materi
genetik dengan sitoplasma
 Berfungsi sebagai barier
 Terdiri dari:
1. Membran luar = Selaput
sistolik
2. Membran dalam =
Selaput nukleoplasmik
3. Ruang perinukleus =
diantara kedua membran
 Kedua membran menyatu
pada suatu daerah yang
 Merupakan kompleks
protein yang menembus
kedua lapis selubung inti
 Pori ini berfungsi sebagai
gerbang keluar masuknya
molekul dari nukleus ke
sitoplasma atau sebaliknya
dengan cara difusi
 Pori nukleus dibentuk oleh
suatu kompleks yang disebut
Nuclear Pore Complex
(NPC).
Merupakan cairan inti atau kariotin yang
bersifat transparan dan semisolid
Mengandung kromatin, granula, nukleoprotein
dan serabut protein-skelet
Berfungsi memberi bentuk pada inti sel, terlibat
dalam aktivitas inti sel baik pada proses
replikasi DNA, transkripsi dan post transkripsi.
Certain long string-like structures that appeared in the
nuclei of cells took stains very well. They were given the
name chromosomes (i.e., colour bodies) in 1888.
 Chromosome as a basis of heredity
 Chromosome number and shape are
species specific.
 The nucleolus is a prominent
sub-nuclear structure that is
not bound by a membrane and
resides within the nuclear matrix
 The size of the nucleolus depends on the metabolic
activity of the cell, with large nucleoli found in
cells that are actively engaged in protein synthesis.
 Eukaryotic cells often contain a single nucleolus,
but several are also possible. The exact number of
nucleoli is fixed among members of the same species
 Nucleoli is the site of rRNA transcription and
processing, and of ribosome assembly (pre-ribosomal
protein)
Ribosom

 “Ribosom adalah organel kecil tidak bermembran
yang ditemukan di dalam semua sel dan terlibat
dalam sintesis protein
Poliribosom
Ribosom pada
organela
Struktur Ribosom
 Terdiri dari 2 subunit: subunit besar dan subunit kecil
 Subunit besar berbentuk bulat dengan 3 tonjolan, subunit
kecil berbentuk seperti batang yang terbelah 2

 Struktur ribosom mencerminkan FUNGSInya yaitu


mempertemukan mRNA dengan tRNA dalam sintesis protein
tahap TRANSLASI
 Ribosom subunit kecil merupakan tempat ikatan mRNA
(mRNA binding site) yang membawa kode genetik yang akan
ditranslasi (diterjemahkan) menjadi rantai asam amino
Ribosom subunit besar memiliki 3 situs pengikatan
untuk tRNA
•= situs peptidil-tRNA
•Mengikat tRNA yang membawa rantai polipeptida yangsedang tumbuh
P site
•= situs aminoasil-tRNA
•Mengikat tRNA yang mengangkut asam amino yang akan ditambahkan ke rantai
A site polipeptida

•= exit site
•tRNA yang telah melepaskan asam amino meninggalkan ribosom melalui E site
E site
Pembagian Ribosom

 1. Ribosom bebas  2. Ribosom terikat


 Lokasinya tersebar di  Terikat pada membran (ER,
sitoplasma nukleus, mitokondria)
 Mensintesis protein yang  Membuat protein yang
berfungsi di sitosol, ex. Enzim berfungsi di dalam sistem
endomembran atau protein
pada glikolisis sekresi, ex. Enzim dalam
vesikel sekresi; sel pancreas
yang mensekresi enzim
pencernaan memiliki ribosom
terikat dalam jumlah banyak
Golgi Apparatus
 The Golgi Apparatus is also  The name comes from
known as the Golgi Italian anatomist Camillo
Complex or Golgi Body. Golgi, who identified it in
 It is part of the 1898.
endomembrane system.  Location: near the nucleus &
floating in the cytoplasm
Structure
 smooth, curvy structure.
 consists of flattened sacs (with a
single membrane) which are
stacked like pancakes
 It has a front end and a back end.
The front end is called the cis face
and the back end is called the
trans face.
 cisternae are the flattened
membrane folds and secretory
vesicles which are what the cell
discharges.
Function

 Apparatus golgi as a central delivery system for the
cell.
 Collection, packaging, and distribution of material.
 targeted to the plasma membrane, lysosomes or
endosomes
 receives materials for transportation through the cis
face and sends the materials through to the trans face
once they are packaged and modified into the vesicles.
Endoplasmic Reticulum

 Endoplasmic reticulum (ER) is a continuous single
membrane system but consists of various domains that
perform different functions
 Structurally distinct
domains of this organelle
include the rough and
smooth ER
The function of ER

1. Synthesis of secretory proteins
2. The folding and modification of proteins in the ER
lumen
3. Synthesis of steroids
4. Detoxification of hydrophobic substances especially
in the liver.
5. The storage of calcium ions and their regulated
release into the cytosol
Smooth ER Rough ER
 Structure: tubular  Has ribosomes on its
 Smooth ER lacks ribosomes surface
on its surface  Makes membrane
 Is attached to the ends of proteins and proteins for
rough ER EXPORT out of cell
 Makes cell products that are  Proteins are made by
used INSIDE the cell ribosomes on ER surface
 SER is abundant only in  They are then threaded
certain cell types, such as in into the interior of the
steroid-synthesizing cells, Rough ER to be modified
liver cells and transported
Mitochondria

 Mitokondria merupakan tempat respirasi seluler, yaitu
proses metabolik yang menghasikan ATP dengan cara
mengambil energi dari glukosa, lipid, dan bahan bakar
lain dengan bantuan oksigen
 Mitokondria merupakan organel yang bersifat dinamis &
semiotonom  dapat berpindah tempat dalam sitosol,
berubah bentuk, berfusi dan membelah menjadi dua
Struktur mitokondria
• Ukuran : diameter 0.2 – 1.0 μm, panjang 1-
4μm
• Jumlah mitokondria bervariasi terhantung
pada jenis organisme dan jenis jaringan: 0
(pada prokariot dan eritrosit) sampai ribuan
1. Mitokondria diselubungi oleh membran
lipid bilayer ganda:
a. membran luar
b. membran dalam
c. ruang antarmembran
2. Matrix mitokondria:
a. enzim-enzim yang terlibat dalam proses
respirasi seluler
b. DNA
c. ribosom
Fungsi mitokondria
1. Memproduksi energi dalam bentuk ATP melalui proses
respirasi seluler
2. Regulasi metabolisme seluler
3. Regulasi membran potensial
4. Kematian sel yang terprogram (apoptosis)
5. Menyimpan Ca
6. Ca-signaling (Ca-evoked apoptosis)
7. Sintesis heme
8. Sintesis steroid
9. Produksi ROS (reactive oxygen species)
10. Detoksikasi amonia (pada hepatosit)
Respirasi seluler pada
mitokondria

Lysosome

 A lysosome is a membrane bag containing digestive
enzymes
 Lysosomes are spherical organelles that contain
enzymes
 Surrounded by single membrane
 The size of lysosomes varies from 0.1–1.2 µm
 Enzyme-filled sacs
 Their shape and size vary depending
on what material is digested
Lysosome Function
1.

Digestion of ingested material from phagocytosis
 Lysosomes pick up foreign invaders such as bacteria, food and
old organelles and break them into small pieces that can
hopefully be used again
 to digest food, the lysosome membrane fuses with the
membrane of a food vacuole and squirts the enzymes inside.
 The digested food can then diffuse through the vacuole
membrane and enter the cell to be used for energy or growth.
Digestive Enzyme
Contain about 40 different  These enzymes work only at
hydrolytic enzymes: low pH (highly acidic) levels
 Lipase, which digests lipids  acid hydrolase
 Amylase, which digest  The only thing that keeps the
carbohydrates (e.g., sugars) cell itself from being digested
 Proteases, which digest is the membrane surrounding
proteins the lysosomes.
 Nucleases, which digest  Uncontrolled release of
nucleic acids lysosome contents into the
cytoplasm can also cause cell
death (necrosis).
Lysosome Function

2. Autophagy & Cell Death
 Lysosomes pick up foreign invaders such as bacteria,
food and old organelles and break them into small
pieces that can hopefully be used again
 Autophagy may also lead to autophagic cell death, a
form of programmed self-destruction, or autolysis, of
the cell, which means that the cell is digesting itself
Function of lysosomes

Peroxisomes

 Peroxisomes are vesicles than contain enzymes
 The enzymes in these organelles use up oxygen and
produce hydrogen peroxide.
 Peroxisomes are abundant in the liver where they
produce bile salts and cholesterol and break down fats.
 Surrounded by a single membrane
 Diameter of 0.1 to 1.0 um.
Peroxisomes

 The site of synthesis and degradation of hydrogen
peroxide (H2O2), a highly reactive and toxic
oxidizing agent.

mentransfer
hidrogen (dari
berbagai substrat) mengubah H2O2
ke oksigen dan menjadi air dan
menghasilkan oksigen
hidrogen peroksida
(H2O2)
Function

to house many metabolic pathways that are involved in
various aspects of lipid metabolism:
1. Enzymes involved in the degradative oxidation
2. The early steps in the synthesis of ether glycerolipids or
plasmalogens
3. The formation of bile acids, dolichol, and cholesterol
4. The catabolism of purines, polyamines, and amino acids,
5. Detoxification of reactive oxygen species such as
hydrogen peroxide

 Cyto + skeleton = “cell skeleton”
 Internal framework of cell
 The cell also have skeleton, like our
body
1 2 3

Microtubules Microfilaments/
Intermediate
(MTs) Actin Filaments
Filaments
(IFs) (Actin)
Each of the 3 types of cytoskeletal filament is a
polymer of protein subunits held together by
weak, noncovalent bonds
Structure of Microtubule

 Tubular structures, hollow, relatively rigid
 Diameter 25 nm, a wall thickness 4 nm, length between 250 nm-
25 μm
 Compose of globular proteins arranged in longitudinal rows,
termed protofilaments
 Each protofilament is assembled from dimeric building blocks
consisting of 1 α-tubulin & 1 β-tubulin subunit
 In cross section, microtubules are seen to consist of 13
protofilament aligned side by side in a circular pattern
 One end of a microtubue is known as the plus end and is
terminated by row of β-tubulin subunit. The opposite end is the
minus end, and is terminated by a row of α-tubulin subunit
Structure of microfilament (actin)

Intermediate Filament

 Unlike microtubules and microfilaments, intermediate
filaments are assembled from a large number of different
IF proteins.
 The assembly of intermediate filaments probably
proceeds through several intermediate structures, which
associate by lateral and end-to-end interactions
 Intermediate filaments are much more stable than
microfilaments and microtubules
 Major degenerative diseases of skin, muscle, and neurons
are caused by disruption of the IF cytoskeleton or its
connections to other cell structures
Struktur IF

 2 Monomer IF 
dimer  tetramer 
IF
Dynamic instability

Dynamic instability model of
microtubule growth and shrinkage

 Assembly of tubulin dimers


requires a GTP molecule
bound to the β-tubulin subunit
Cytoskeleton function

Anchoring Cell
Provide cell shape Organeles
Cytoskeleton function

Intercellular Anchoring
Cytoskeleton function

Aids in Cell Locomotion

Aids in Cell Division


Microtubule Dynamics in
Mitosis

the mitotic apparatus (microtubules) is designed to attach


and capture chromosomes, align the chromosomes, and
then separate them so that the genetic material is evenly
partitioned to each daughter cell. Fifteen hours later, the
whole process is repeated by the two daughter cells.
dr. Alvi Milliana
Sublethal Acute injury
chronic injury

 Cellular
adaptation
 intrascellular
accumulatio
n
 Pathologic
calcification
 Cell ageing
Apoptotic cells may be isolated in tissues and not affect other cells. Necrotic
cells in tissues dispense hydrolytic enzymes that damage their neighbors.
Necrosis
 Definition:
Necrosis is unprogrammed death of cell & living tissue. A
form of cell injury which result in the premature death of
cell in living tissue by autolysis.
Causes:
the most common causes of cell death are: viruses,
ischaemia, bacterial toxins, hypersensitivity, and ionizing
radiation
 Morphologic changes:
The changes don’t appear in the affected cells by light
microscopy before 2-6 hours according to the type of the
affected tissue
Mechanisms leading to necrotic cells
Coagulative necrosis—
kidney infarction
myocardial infarction

Gangrenous necrosis Liquefaction necrosis


Apoptosis
Definition:
 It is programmed death of cells in living tissues. It is
an active process differing from necrosis by the
following points:
 Occurs in both physiological and pathological
conditions.
 Starts by nuclear changes in the form of chromatin
condensation and fragmentation followed by
cytoplasmic budding and then phagocytosis of the
extruded apoptotic bodies.
 Plasma membrane are thought to remain intact
during apoptosis until the last stage so does not
initiate inflammatory reaction around it.
APOPTOSIS
While committing suicide
cells:
 Shrink
 Chromatin Degraded
 Mitochondria Break
Down
 Break into Membrane-
bound Fragments
 Phosphatidylserine
Exposed
 Phagocytic Receptors
 Inflammation Inhibition
Major criteria of Apoptosis

1. Morphological changes
2. Nuclei (Chromatin) condensation
3. DNA fragmentation
4. Cells fragment into membrane-bound bits

Bits are phagocytosed by macrophages


Examples of physiologic and pathologic cases
accompanied with apoptosis:

1. Programmed cell death during embryogenesis.
2. Hormone dependent cell involution in case of
endometrial cell break down during menstrual
cycle.
3. Normal turnover in proliferating tissues (e.g.
intestinal epithelium)
4. Cell death in tumours during regression
induced by cytotoxic drugs or irradiation.
5. In some viral disease e.g. viral hepatitis in which
apoptotic cells are known as councilman bodies.
Mechanisms of apoptosis
APOPTOSIS NECROSIS
Physiological or pathological Always pathological
Single cells Sheet of cells
Energy dependent Energy independent
Cell shrinkage Cell swelling
Membrane integrity maintened Membrane integrity lost
Role of mitochondria & cytochrome C No role for mitochondria

No leak of lysosomal enzyme Leak of lysosomal enzymes


Characteristic nuclear changes Nuclei lost
Apoptotic bodies form Do not form
DNA cleavage No DNA cleavage
Activation of specific proteases No activation
Regulated process Not regulated
Evolutionary conserved Not conserved
Dead cells ingested by neighbouring Dead cells ingested by neutrophils &
cells macrophages

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