Dr. dr. H. Busjra M.

Nur MSc
Dept. Fisiologi FKUI / FKKUMJ
Main Cell Functions
 Movement
 Conductivity
 Metabolic absorption
 Secretion
 Excretion
 Respiration
 Reproduction
Part of the Cell
 Cell Membrane
 Cytosol
 Organelles
 Nucleus
Cell Membrane
= plasma membrane
 Separates the extracellular and intracellular
environments
 Regulates molecular traffic into and out of the cell 
channels and carriers
 Sensitivity  Receptor
Membrane Protein
 Anchoring proteins
 Recognition proteins
 Enzymes
 Receptors
 Carrier proteins
 Channels
Cytosol
 Lots of potassium
 Lots of protein (ec: enzyme)
Mitochondria
 Oxidative phosphenylation  ATP
 Regulation of apoptosis
 Hundreds to thousands in each eukaryotic cells
 Sausage shape in mammals
 Have their own genom
Lysosomes
 Is more acidic than the rest of cytoplasm
 External material (endocytosed bacteria, worn-out cell
components)  ingested in them
 When a lysosomal enzyme is congenitally absent 
lysosomal storage diseases
Peroxisomes
 Found in the microsomal fraction of cells
 Surrounded by a membrane
 The membrane contains a number of peroxisome-
specific proteins  transport of substances into / out
of matrix of the peroxisome
 The matrix contains > 40 enzymes  catalyze a variety
of anabolic / catabolic reactions
Cytoskeleton
 A system of fibers
 Maintains the structure of the cell
 Permits it to change shape and move
 Made up of microtubules, intermediate filaments and
microfilaments and proteins that anchor them and tie
them together
Microtubules
 Long, hollow structures
 5 nm walls
 A cavity 15 nm in diameter
 Made up of two globular protein (α and β tubulin)
 The assembly is facilitated by warmth and disassembly
by cold and other factors
Microtubules
 Constant assembly and disassembly  dynamic
portion of cell skeleton
 The tracks for transport vesicles, organelles (such as
secretory granules) and mitochondria from one part of
the cells to another
 Form the spindle which moves the chromosomes in
mitosis
Microtubules
 Microtubules assembly is prevented by colchicine and
vinblastine
 Paclitaxel (Taxol), anticancer drug  binds to
microtubules and makes them so stable that organelles
cannot move  mitotic spindles cannot form  the
cells die
Intermediate filaments
 8-14 nm in diameter
 Connect the nuclear membrane to the cell membrane
 Form a flexible scaffolding for the cells
 Help it resist external pressure
 Absent: cells rupture more easily
 Abnormal in humans: blistering of the skin
Microfilaments
 Long, solid fiber, 4-6 nm in diameter
 Made up of actin
 Most abundant protein in mammalian cells
 Attach to various parts of cytoskeletons
 Reach to tips of the microvilli on the epithelial
cells of intestinal mucosa
 Also in lamellopodia that cells put out when they
crawl along surfaces
 Actin filaments interact with integrin receptors
and form focal adhesion complexes  points of
traction with the surface  cells pulls itself
Molecular Motors
 Move protein, organelles, and other cell parts (their
cargo) to all parts of the cell
 They attach to their cargo and their heads bind to
microtubules or actin polymers
 Hydrolysis of ATP in their heads  molecules move
 2 types: - producing motion along
microtubules
- producing motion along actin
Centrosomes
 Microtubule-organizing centers (MTOGs)  contain
∂-tubulin
 When a cell divides  centrosomes duplicate
themselves  move apart to the poles
Cilia
 Unicellular: to propel themselves through the water
 Multicellular: To propel mucus and other substances
over the surface of various epithelia
Cell adhesion molecules
- Attached cells to the basal lamina and other cells  cell
adhesion molecules (CAMs)
- Important :
 in embryonic development and formation of the
nervous system and other tissues
 In holding tissues together in adult
 In inflammation and wound healing
 In the metastasis of tumors
Cell adhesion molecules
 Many pass through the cell membrane and are
anchored to the cytoskeleton inside the cell
 Some bind like molecules on other cells (homophilic
binding)
 Others bind to other molecules (heterophilic binding)
 Many bind to laminins (multiple receptors domains in
the extracellular matrix)
Cell adhesion molecules
 Divided into
- integrins : heterodimers that binds to
various receptors
- IgG superfamily of immunoglobulins
- cadherins : Ca++ dependent molecule 
cell to cell adhesion
- selectins : have lectin-like domains that bind
carbohydrates
Cell adhesion molecules
 Fastens cells to their neighbors
 Transmit signals into and out of the cells
 Cells that lose their contact via integrins  apoptosis ↑
Intercellular connections
 Fasten the cells to one another and to surrounding
tissues
 Permit transfer of ions and other molecules from one
cell to another
Nucleus
 Made up of in large part of the chromosomes
 The side where DNA and RNA are made
 Cellular functions ultimately are controlled
The Chromosomes
 Carry a complete blueprint for all the heritable species
and individual characteristics
 Occur in pairs, except in germ cells
 Made up of a giant molecule of DNA
(deoxyribonucleic acid)
The human genome
 Finally mapped
 About 30.000 genes
 About 85.000 mRNAs
Nucleus
 DNA  gene  chromosome
↓
 RNA  cytosol  produce proteins
mRNA (messenger RNA)
tRNA (transfer RNA)
rRNA (ribosomal RNA)
DNA & RNA
 Information stored in DNA and RNA direct the
synthesis of proteins that determine the shape and
function of a cell
DNA
 When DNA is damaged  entry into mitosis is
inhibited  giving the cell time to repair
 Failure to repair damaged DNA  leads to cancer
 The cell cycle is regulated by proteins: cyclins and
cyclin-dependent protein kinases
Genetic aspect of cancer
 Some cancers are caused by oncogenes  genes
that are carried in the genomes of cancer cells and
responsible for producing their malignant
properties
 Derived by somatic mutation from proto-
oncogenes (normal genes that control growth)
 > 100 oncogenes
 Another genes  produces protein  suppress
tumor
Oncogenes
 The p53 gene is mutated in up to 50% of human cancer
patients  produce p53 proteins  fail to slow the
cycle cell and permit other mutation in DNA
 The accumulated mutations cause cancer
 The BRCA-1 gene  breast cancer
Regulation of gene expression
 Each nucleated somatic cell  full genetic message 
great differentiation and specialization in the
functions
 Only small part of the message are normally transcribe
 normally maintained in repressed state
  gene are controled: spatially & temporally
Regulation of gene expression
 What turns on genes in one cell and not in other
cell
 What turns on genes in one cell at one stage of
development ad not at other
 What maintains orderly growth in cells and
prevents the uncontrolled growth (cancer)

 DNA sequences promotes orderly transcription

of the gene (cis regulation)
 transciption factors are product of other gene 
mediate trans regulation
Molecular medicine
 Antibiotics: inhibit protein synthesis in bacteria
 Antiviral (acyclovir, ganciclovir): inhibit DNA
polymerase
Siklus Kehidupan Sel
 Jumlah sel tubuh: 75-100 triliun
 Sel hidup dalam fase: - interphase
- mitosis
 Pembelahan sel
- Mitosis
- Meiosis
- Sitokinesis
Fase Pembelahan Sel
Fase Mitosis (M phase):
 Prophase
 Metaphase
 Anaphase
 Telophase
Periode bermitosis
 Sel otot dan sel saraf (long-lived cells) hampir tidak
bermitosis
 Sel epitel (kulit, mukosa) dalam hari / jam
Telomeres
 Cell replication involve:
- DNA polymerase of chromosomes
- transcriptase: telomeres of chromosomes 
telomerase
 High telomerase activity ( includes most cancer cells)
 keep multiplying indefinitely
Kehidupan sel
 Sel membelah diri  sebentar
 Sebagian besar hidup sel dalam masa interphase:
- fungsi sel normal  fase Go
- persiapan untuk membelah
diri  fase G1. S dan G2
 Sel otot lurik & sebagian besar neuron  Go terus menerus
(tidak pernah membelah diri)
 Stem cells  membelah diri berulang-ulang  tidak
pernah masuk Go
Interphase
 Fase G1 (8-12 jam) : sel siap membelah diri, dibuat
cukup mitokondria, sitoskeleton, retikulum
endoplasmik, ribosom, dll.
 Fase S (6-8 jam): menduplikat kromosom, al:
replikasi DNA
 Fase G2 (2-5 jam) : selesaikan replikasi sentriol 
masuk fase M (mitosis)
 Fase Go = fase berfungsi normal  sangat
bervariasi
Apoptosis
 Suatu program kematian sel
 Setiap sel punya jalur yang bila diaktifkan
menyebabkan sel bunuh diri dg menghasilkan ensim
protein yang menghancurkan sel itu.
 Peristiwa normal dlm kehidupan
Peran Apoptosis
 Bagian normal dari pertumbuhan
 Penting pada tissue turnover pd dewasa
 Penting pada sistem imun  buang sel yang terinfeksi
virus
 Membuang sel yang tidak diperlukan / menghambat
homeostasis: sel tua, sel rusak, sel bermutasi (sebelum
menjadi kanker)
Sitokin (cytokines)
 = hormon lokal, paracrine factors
 Chemical messenger yg dilepaskan sel untuk
koordinasi aktivitas lokal
 Diproduksi banyak sel untuk komunikasi parakrin,
komunikasi sel ke sel dalam satu jaringan.
 Yg diproduksi sel pertahanan  kerja spt hormon
 Contoh: interferron, prostaglandin
Prostaglandin
 Dihasilkan sel tertentu
 Efek utama pada jaringan setempat
 Efek sekunder pada jaringan / organ lain  seperti
hormon
Hormon
 Chemical messenger yang dilepaskan pada satu
jaringan, masuk aliran darah  sel spesifik pada
jaringan lain
Extracellular chemical messenger
 Parakrin
 Neurotransmiter
 Hormon
 Neurohormon
Chemical messenger
 First messenger : berikatan dg reseptor  respon
intrasel
- buka / tutup pintu spesifik
- transfer sinyal ke chemical messenger
intrasel (second messenger )
 Second messenger : mencetuskan serial biokimiawi
dlm sel
  transduksi sinyal
Transduksi Sinyal
 Dicetuskan oleh ikatan chemical messenger pd
reseptor
 Tujuan: - ↑ fungsi
- pertumbuhan
- survival
- replikasi (reproduksi sel)
Membrane channels
 Leak channels : selalu terbuka
 Gated channels : terbuka / tertutup oleh stimulus
Gated channels
 Chemical messenger berikatan dg reseptor membran
spesifik
 Mengubah kelistrikan membran sel
 Deformasi mekanik pd channels
cAMP & cGMP
 Suatu second messenger
 Rangsang reseptor  protein G  adenil siklase 
cAMP & cGMP  aktifkan protein kinase  fosforilasi
protein  sel > aktif
 Dihidrolisis oleh PDE (phosphodiesterase)
Modifications of second messenger pathways
 Jumlah reseptor
 Afinitas reseptor
Reseptor sel
Terdapat pada:
 membran sel
 sitoplasma
 nukleus
Reseptor Membran Plasma
 Terutama untuk menangkap ligand
 Ligand : - hormon
- neurotransmiter
- antigen
- komplemen
- lipoprotein
- mikroba infeksi
-obat
- metabolit
Reseptor Adrenergik
Terdapat pada dinding sel target
Reseptor α  α1 dan α2
Reseptor β  β1 dan β2
Reseptor α  > sensitif thd norepinefrin
Reseptor β1 sama sensitif epi – norepi
Reseptor β2 > sensitif thd epinefrin
Obat: α blocker
β blocker
β2 agonist
Reseptor Adrenergik:

α1 : dilatasi pupil , konstriksi arteriol

α2 : kontraksi otot saluran cerna ↓
β1 : denyut jantung: ↑
Β2 : saluran napas: dilatasi
Reseptor obat
 Anestetika
 Opiat
 Endorfin
 Enkefalin
 Antibiotik
 Kemoterapi kanker
 Digitalis
Reseptor mikroba
 Mengikat : bakteri, virus dan parasit
 Reseptor antigen pada limfosit dll: mengenal dan
mengikat antigen  mengaktifkan respon imun dan
inflamasi
Reseptor Endorfin
 Endorfin = opiate like peptide  dari
kelenjar hipofisa
 Reseptor sangat banyak terdapat pada jalur saraf
penghantar rasa nyeri
 Reseptor + opiat  perubahan permeabilitas
membran  modulasi rasa nyeri
Penyakit
 Diabetes melitus: jumlah reseptor insulin ↓ sbg respon
thd elevasi kronik insulin dlm darah
 Myasthenia gravis: reseptor asetilkolin rusak
 Kolera: toksin kuman menghambat inaktivasi cAMP
pada sel dinding usus.
 cAMP merangsang sekresi cairan ke lumen
Growth factors
 Polypeptides / proteins
 One group:
- insulin-like growth factors
- nerve growth factors
- activins
- inhibins
 Second group: Cytokines
 Colony-stimulating favtors  regulate
proliferation and maturatin and maturation of red
and wihte
Hypercalcemia of malignancy
 Cause by bone metastases
 Produce by PGE from the tumor
 Also by circulating PTH (humoral hypercalcemia of
malignancy)
Hormones & Cancer
 Estrogen-dependent breast carcinoma
 Often have a remission when their ovaries removed
 Tamoxifen: inhibit the action of estrogens 
remission
 Ca prostate  androgen-dependent