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BODY

PROTEIN
Enzyme
Receptor
Hormone
Growth Factor
Immunoglobulin
Interferon, Interleukin, Cytokine
Adhesions molecules
HLA/MHC

STRUKTUR

PROTEIN
SIFAT PROTEIN
FUNGSI PROTEIN
PEMBENTUKAN PROTEIN
DISTRIBUSI PROTEIN
PEMERIKSAAN PROTEIN

Proteins are composed of subunits called amino acids

Biokimia

: DNA adalah Polymer dari


Desoxyribonucleotide (Basa, zat Gula dan 1
atau lebih gugus Phosphat)
Zat Gula : -D-2 Desoxyribose (Ribose)
Ikatan N-Glykosida antara Desoxyribose
(C1) dengan Pyrimidin (N1) atau Purin (N9)

DNA Base Pairing


A G C G A T C T G G
T C G C T A G A C C
Double helix consists of 2
complimentary strands of DNA.

Genes
Segments of DNA code for proteins (or
parts of proteins)
Each coding segment is called a gene
One gene codes one protein (or part of)
Genes contain the information which
makes us what we are

Gene Structure
Every

three bases of DNA is called a codon


Each codon specifies an amino acid which
join together to form the protein
eg ATG = methionine = START
TAA = STOP
TAG = STOP
TGA = STOP

Protein Synthesis Transcription


Each

gene codes for a protein


DNA sense strand acts as template
and is transcribed into messenger
RNA (mirror image of the DNA but
Uracil instead of Thymine)
DNA
mRNA

ATC G G
UAG C C

Protein Synthesis- Translation


Introns

are spliced out of the mRNA


mRNA leaves the nucleus
In the cytoplasm, ribosomes attach to the
mRNA ensuring the correct amino acid, for
each codon, is added to a growing chain of
amino acids which forms the resulting
protein.

Amino acid assembly during translation occurs on ribosomes;


tRNA serves as the crucial adaptor molecule

Nukleotida 1.
(5)
U

Nukleotida 2.

Nukleotida 3.

Phe

Ser

Tyr

Cys

Phe

Ser

Tyr

Cys

Leu

Ser

STOP

STOP

Leu

Ser

STOP

Trp

Leu

Pro

His

Arg

Leu

Pro

His

Arg

Leu

Pro

Gln

Arg

Leu

Pro

Gln

Arg

(3)

Ile

Thr

Asn

Ser

Ile

Thr

Asn

Ser

Ile

Thr

Lys

Arg

Met

Thr

Lys

Arg

Val

Ala

Asp

Gly

Val

Ala

Asp

Gly

Val

Ala

Glu

Gly

Val

Ala

Glu

Gly

Protein Synthesis
transcription

DNA

RNA

Protein

translation

Mutations
A change in the DNA sequence of the
gene
All cells acquire mutations as they
divide

-6

rate of approx 10 per gene per cell

Mutations can alter protein product of


DNA, stop gene working or activate
gene

Types of Mutation
Deletion

- DNA missing
Insertion - extra DNA inserted
Expansion (Amplification) - DNA
repeat size has increased
Point Mutation - change in one base

Types of Mutation
(in coding sequence)

AGC TTC GAC CCG


Wild type
AGC TCG ACC CG
Deletion
AGC TTC CGA CCC G
Insertion
AGC TTC TTC GAC CCG
Expansion
ATC TTC GAC CGG
Point mutation

POINT MUTATION
UAA
(Termination Codon)
UCA
(Codon for Serine)
UCU
(Codon for Serine)
CCA
(Codon for Proline)

Cancer
Cancer is a group of diseases in which
genetically damaged cells proliferate
autonomously
The genetic damage consists of mutations
(eg.point mutation, deletion, insertion) and
chromosomal rearrangements or losses
Such changes result in the loss or altered
function of molecules involved in cell growth
or proliferation.

Genes in Cancer
Mutations could affect Protooncogenes
or Tumorsuppressor genes.
Protooncogenes code for a variety of
growth factors, growth factor receptors,
enzymes or transcription factors that
promote cell growth and/or cell division.
Mutated version of Protooncogenes
(erbB, ras, jun, fos, myc, etc) are called
Oncogenes

Genes in Cancer
Proto-oncogenes

are activated to
oncogenes by various mechanisms.
1. Promoter insertion
2. Enhancer insertion
3. Chromosomal translocations
4. Gene amplification
5. Point mutation

Oncogen

Cancer

abl
Translocation
CML
myc
Translocation
Burkitts Lymphoma
erb B
Amplification
Epithelcarcinoma,
Astrocytoma,
Ca Oesophagus
neu
Amplification
Adeno Ca (Mammae,
Ovarium, Gaster)
myc
Amplification
Ca- Mammae, Lung,
Uterus, Oes
N-myc
Amplification
Neuroblastoma, Ca.Paru

Int-2

Amplification

Ca-Oesophagus

Apoptosis
Programmed

cell death
Intracellular machinery responsible for
apoptosis is called caspases.
Caspases

Synthesized in the cell as inactive precursor called


procaspases
Usually activated by cleavage at aspartic acids by
other caspases.

Tumor suppressor genes


Play

an important role in tumorigenesis.


Involved in the control of abnormal cell
proliferation.
Loss or inactivation : association with the
development of malignancy.

Tumor suppressor genes


The majority of p53 mutations (80%) in
breast cancer are missense, while 20%:
nonsense mutations, deletions, insertions
P53 protein (21kD) normally inhibits Cdk
(Cyclin dependent kinase) enzymes.
Recent evidence indicates that other
damaged or deleted Tumorsuppressor
genes may code for enzymes involved in
DNA Repair mechanisms.
If DNA repair mechanisms are incomplete,
a complex mechanism involving P53 leads
to programmed cell death or Apoptosis

Carcinogenics
Radiant energy
Chemical compounds
Viruses ( DNA virus,RNA virus, Adeno
virus)

These act by causing mutations or by


introducing novel genes into cells

Familial conditions (Tumor suppressor


genes)
Oxidative damage to DNA increase the
mutations rate

Photodimerizatio
n
Exposure to UV light
can cause adjacent
thymines to
covalently link.
This results in a
distortion of the DNA
molecule and
breaks the hydrogen
bonding with the
adenine.

UV light
|
| |
A C T

|
T

T
|

A C G T
| |
| |

G A
| |

| |
| |
G C A T
A
|

thymine
dimer
|
|
A C

| |
| |
G C A T

T
|

C G T
|
| |

G
|

A
|

Carcinogenesis (Colorectal
Cancer)

Tumor metastasis
Metastasis is the most dangerous
property of tumor cells
The cell grow as secondary tumors
Many changes have been documented at
the surfaces of malignant cells
Some are: alterations in transport
property, diminished adhesion, loss of
certain antigens etc.