Biology of the cell

&
Principle of Genetics

Dwi Ari Pujianto, Ph.D

Department of Medical Biology

 Life develops from one cell

Sea urchin Mouse Fucus seaweed

 The Discovery of Cells
• First compound microscope  was discovered
at the end of 16th century

• The discovery of cells (1665) 

– Robert Hooke  Cork contains little porous (like

honeycomb)  the pores  Cells

– Anton van Leeuwenhoek (Dutchman)  examine a

drop of pond water
 The Discovery of Cells (2)
• In 1838, Matthias Schleiden  Plants
were made of cells and the plant embryo
arose from a single cell

• In 1839, Theodor Schwann  the cells of

plants and animals are similar structure 
proposed “Cell Theory”
 Cell Theory (1839)
• All organisms are composed of one or
more cells

• The cell is the structural unit of life

• Cells can arise only by division from a pre-

existing cell (was added in 1855 by Rudolf
Virchow)
 Two Different Classes of Cells

• Prokaryotic (pro = before, karyon =

nucleus)  Bacteria

• Eukaryotic (eu = true, karyon =nucleus) 

Protist, Fungi, Plants and Animals
 Features held in common
by prokaryotic and Eukaryotic

Similar construction of plasma membrane

Genetic information  identical code

Similar mechanism for transcription and

translation

Shared metabolic pathways  e.g. Glycolysis &

TCA cycle
 Features of Eukaryotic cells
not found in prokaryotes

Nucleus and cytoplasm separated by a nuclear

envelope containing complex pore structures

Complex chromosome composed of DNA &

associated protein

Organelles are enclosed in the membrane

system

Specialized cytoplasmic organelle for aerobic

respiration  Mitochondria
The three major divisions of living world
The structure of Prokaryote
Structure of Eukaryotes
Proof that living things are from
a common ancestor cell
Evolutionary Origins of Organelles
Evolutionary origin of Mitochondria
 Nucleus
• Nucleus  contains genome (aside from
mitochondrial and chloroplast DNA)

• Principal site of DNA and RNA synthesis

(DNA replication and Transcription)
 Cytoplasm
• Outside nucleus, inside the cell membrane

• Consist of cytosol and the cytoplasmic

organelles

• Cytosol is the site of protein synthesis and

degradation

• Cytosol also perform most of the cell’s

intermediary metabolism  to form
macromolecules
 Endoplasmic Reticulum (ER)
• Rough ER has many ribosomes bound to its cytosolic
surface

• Synthesis both soluble and integral membrane protein

• Most proteins are secreted or for other organelles

• Smooth ER  lack bound ribosomes

• ER also produces most of the lipid, stores Ca2+ ions

 Golgi apparatus
• Discovered by Camillo Golgi in 1897

• Consist of organized stack of disclike

compartments called Golgi cisternae

• Receives proteins and lipids from ER,

modifies them (Glycosylation,
phosphorylation, signal sequence) and
dispatches to various destinations
 Mitochondria and Chloroplast
• Generate most of the ATP that cells use to
drive reactions requiring an input of free
energy

• Chloroplasts are a specialized version of

plastids which can also have other
function  storage of food or pigment
 Lysosomes & Endosomes
• Lysosomes contains digestive enzymes 
degrade defunct intracellular organelles,
macromolecules & particles taken from
outside by endocytosis

• On their way to lysosomes, endocytosed

materials must first pass through a series
of organelles called endosomes
 Peroxisomes
• Small vesicular compartment

• Contains enzymes used in various

oxidation reactions  produce H2O2

• Peroxidase eliminates H2O2

 Membran Plasma

melingkupi, menjadi batas antar sel dan antar organel

mempertahankan perbedaan antara sitosol dan

lingkungan ekstraseluler

Pada sel eukariotik  Membran organel mempertahankan

spesifisitas

Ion gradient pada membran  sintesa ATP 

pergerakan molekul lewat membran

Mengandung protein yang bertindak sebagai 

sensor/reseptor thd signal dari luar
 General Structure of the biological membranes

# lapisan tipis lipid dan molekul protein diikat bersama oleh ikatan noncovalent

- Molekul lipid  double layer (tebal 5 nm)  lipid bilayer,

impermeable thd sebagian besar molekul yang larut dlm air

- Molekul protein  tertanam pada lipid bilayer (protein transmembran)

 memfasilitasi hampir semua fungsi membran sel :

- Transport molekul spesisfik

- katalisasi reaksi sintesa ATP
- Reseptor
- Menghubungkan sitoskeleton dg extraseluler matrix
 General structure of cell membrane

Electron micrograph of human RBC

 Lipid Bilayer

-Struktur dasar pada membran sel  proporsi lipid = 50% dari total massa
- membran lipid bersifat amphiphilic

Hydrophilic (water-loving) / polar

Amphiphilic
Hydrophobic (water-fearing) / non polar

- Lipid yang paling banyak adalah  phospholipid  yang tersusun oleh

-Satu polar head group
-Dua hydrophobic hydrocarbon tail (fatty acids)  14 -24 atom carbon
-Cis-double bond  unsaturated  small kink  menentukan
membrane fluidity

-Phospholipid yang paling sering ditemukan pada membran  phosphoglyceride

 Phosphoglycerides

-Mempunyai 3 atom carbon pada Glycerol backbone

- Dua rantai asam lemak (fatty acid) dihubungkan oleh ikatan ester pada glyserol,
sedangkan atom ke 3 dari glyserol berhubungan dengan phosphate group

-Phosphate group berhubungan dengan salah satu head group  Choline,

ethanolamine, serine

-Kombinasi dari beberapa fatty acid dan head group 

- Phosphatidylethanolamine,
Phosphoglyceride utama
- Phosphatidylserine Pada sel mamalia

- Phosphatidylcholine
Bagian-bagian dari molekul phosphogliceride
 Protein Membran

Lipid bilayer  struktur dasar membran biologi

Protein membran  berperan dalam fungsi spesifik

Myelin membran  < 25% adalah protein (less functions)

Membran yg terlibat dlm produksi ATP  75% protein

 Berbagai cara protein berasosiasi dengan lipid bilayer

Glycosylphosphatidylinositol (GPI) anchor

Integral membrane protein

Soluble protein
Transmembrane Protein In the cytosol
With hidrophobic & hidrophilic Peripheral membrane protein
regions
 Membran transport

Dikarenakan hydrophobic interior membran  sebagian besar molekul polar tidak bisa masuk 
mempertahankan konsentrasi solute dlm sitosol

Sel menggunakan transmembran protein untuk transport:

- inorganik ion,
- molekul organik yg larut dlm air

Pentingnya transport membran tercermin dlm banyaknya gen yang mengkode transport protein

15 – 30% dari seluruh protein membran

Transport protein  Transporter (Mempunyai bagian yg bergerak untuk

mentransport molekul spesifik melewati membran)

Channel (Dgn pori-pori hydrophilic ) pasive transmembran

movements untuk ion anorganik

Kombinasi antara selective passive permeability dan active transport 

perbedaan komposisi antara sitosol dan cairan ekstraseluler
 Prinsip membran transport

-Pada protein-free lipid bilayer

- Molekul berdifusi berdasarkan gradien konsentrasi

- Dari konsentrasi tinggi ke Konsentrasi yang rendah

-Faktor yang menentukan laju difusi :

- ukuran molekul
- Kelarutan dalam minyak
- Muatan

-Makin kecil ukuran molekul dan makin larut dlm minyak (makin hidrofobik dan makin
non polar)  makin cepat berdifusi dengan lipid bilayer

- Iipid bilayer  highly impermeable terhadap molekul yg bermuatan (ion)

Relative permeability of synthetic lipid bilayer to different classes of molecules
 Terdapat 2 klas utama Membran Transport Protein

Transporter (carrier atau permease)

- mengikat solute yang spesifik untuk ditransport

- Protein ini mengalami serangkaian perubahan konformasi untuk men-

transfer solute yg telah terikat melewati membran

- Bisa aktif dan pasif

Channel

- Interaksi dengan solute lemah

- Terbentuk aqueous pores  terbuka  specific solutes (inorganic ion

dengan ukuran dan muatan yang sesuai) bisa lewat

- Pasif transport
Transporters and Channel Proteins
Transport aktif and pasif
Tiga cara transport aktif melalui protein transporter
 Ion Channels

Two important properties distinguish ion channels

from simple aqueous pores

1. Ion selectivity  permitting some inorganic ions to pass but not others

2. Ion channels are not continuously open

 Gated, which allow to open briefly and then close again

 Prolonged stimulation  desensitized

The gating of ion channels
Human Genetics
Mendel’s monohybrid cross
 Mendel’s Key Principles

The Principle of Dominance (genetic function)

In heterozygote, one allele may conceal
the presence of another

The Principle of Segregation (Genetic transmission)

In heterozygote, two different alleles segregate from each other
during the formation of gametes
Dihybrid Cross: The principle of independent assortment
Mendel’s
Dihybrid Cross
 The 3rd Mendel’s Principle

• The Principle of independent Assortment:

The alleles of different genes segregate (assort)
independently of each other
 Achondroplasia

A = Achodroplasia Aa x Aa
a = normal

AA x aa
AA = Achondroplasia
Aa = Achondroplasia
Aa = Achondroplasia Aa = Achondroplasia
Aa = Normal
 Albinisme

A = Gen encoding the formation of melanin (Normal)

a = mutated allele that causes disruption in melanin production

aa x AA Aa x Aa
(albino) (normal)

AA = normal
Aa Aa = normal 75%
(Normal) Aa = normal
aa = albino 25%
 Mendelian inheritance in human
pedigree

-Pedigrees  Diagrams that show the relationship

among the member of a family

-Traits caused by dominant alleles  Every affected

individual is expected to have, at least one, affected
parent

-Recessive traits  Occur in individuals whose parents

are not affected  Sometimes, several generations of
pedigree data are needed to trace the recessive alleles

(c) Recessive trait

 Genetic Counselling

The risk depends on 2 factors

(1) Probability that R is a heterozygous carrier

(2) Probability that he will transmit albino allele The risk that T will be aa =
to T if he actually is carrier
[Probability that R is Aa] x [Probability that R

Transmit a, assuming that R is Aa]

= (2/3) x (1/2) = (1/3)

 Extension of Mendelism
• Incomplete dominance
• codominance
• Multiple alleles
• Gene interaction
• Epistasis
• Pleiotropy
 Incomplete Dominance
In Antirrhinum majus (snapdragons)

The intensity of pigmentation depends on the amount of product specified by the color gene
 Codominant
The two alleles contribute independently to the phenotype of the heterozygotes

• M-N blood types

• Determined by two alleles of a gene on chromosomes 4

• LM = M blood type

• LN = N blood type

• LMLN = MN blood type

Multiple alleles

c+ > cch > ch > c

 Penetrance
When individuals do not show a trait even though they have the appropriate genotype

- Incomplete penetrance

Example : Polydactyly  The presence of extra finger and toes

 Dominant mutation (P)

III-2 must be a carrier (both his mother & three of his children are polydactyly),
 No extra fingers or toes
 Expressivity
If a trait is not manifested uniformly among the individuals that show it

Example : Variable expressivity of the lobe mutation (dominant mutation)

in Drosophila

Each fly is heterozygous for the mutation  phenotypes vary

 Gene Interaction
When a trait is influenced by more than one gene (Bateson & Pannett)

Comb shapes in chickens

Rose Pea

Walnut Single
 Pleiotropy
When a gene affects many aspects of the phenotype
e.g. gene for phenylketonuria in human beings

Transaminase
Phenylalanine Phenylpyruvic acid
Blocked
In phenylketonuria Phenylalanine hydroxylase

Tyrosinase
Tyrosine Melanin (dark pigment)

Blocked in
albinisme

Homogentisic acid
Blocked in
alkaptonuria
Homogentisic acid oxidase

Fumaric acid + Acetoacetic acid

 Sex-Linked Genes in Human Beings

• A situation where a gene (phenotype

expression) is related to the chromosomal sex of
the individual

• E.g.
– Hemophilia, an x-linked blood-clotting disorder
- unable to produce a factor needed for blood
clotting
– Color blindness, an x-linked vision disorder
- Abnormality in light-absorbing protein
 Non Mendelian Inheritance
• Multifactorial disorders

• Somatic cell genetics disorders

• Mitochondrial disorders
Multifactorial diseases
 Somatic cell genetic disorders
• Mutation after the first cell division 
mosaic

• Mutation on tumor suppressor gene 

cancer
 Mitocondrial disorders
• All derived from the mother
• Transmission to all children of affected
mother
• No risk to the offspring of affected man
• Mitochondria has 10x higher mutation rate
than nuclear DNA
• Phenotype effect depends on the location,
type of mutation, proportion of the
mitochondrial chromosome involved
Examples of Mitochondrial Diseases
CELL CYCLE
The Cell Cycle Control System
 Cyclin-Dependent Protein Kinases (Cdks)

The activity of these kinases rise and fall as the cell

progresses through the cycle

Cyclical changes in Cdk activity are controlled by a

complex array of enzymes and other proteins that
regulate these kinases  the most important are
proteins known as Cyclins
 Four Classes of Cyclin
• G1/S-cyclins : Activate Cdks in late G1  trigger cell-
cycle entry

• S-cyclins : Stimulate chromosome duplication, remain

elevated until mitosis, contribute to early mitotic events

• M-cyclins : Activate Cdks that stimulate entry into

mitosis at G2/M checkpoint

• G1-cyclins : Help govern the activities of the G1/S-

cyclins
Two key components of the cell-cycle control system

Without cyclin,
Cdk is inactive
Cyclin-Cdk complexes in the cell-cycle control system

Anaphase-promoting complex
Or
Cyclosome

APC Destroys the protein securin which normally protect

protein linkages that hold sister chromatids