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Amount and constitution

are created. To study any protein or for that matter, any


molecule in chemistry, one needs to understand its

Reference ranges in CSF

structure first. That is why to study a protein, a biochemist

Substance

Lower limit

Upper limit

Unit

must first find out its amino acid sequence. A protein is

Glucose

50[3]

80[3]

mg/dL

much more complex than a peptide chain with hundreds or

Protein

15[3]

40[4]45[3]

mg/dL

thousands of amino acids bonding together.

RBCs

n/a[3]

0[3] / negative

cells/L

WBCs

0[3]

3[3]

cells/L

The formation of proteins happens at the cellular level. The


recipe or the code for creation of any protein is encoded in

The CSF is produced at a rate of 500 ml/day. Since

the DNA (Deoxyribose Nucleic Acid) molecule. To create

the brain can contain only 135 to 150 ml, large

every protein, the recipe for creation, must first be

amounts are drained primarily into the blood

deciphered from the DNA molecule and then relayed to the

through arachnoid granulations in the superior

site of protein synthesis. The deciphering part is done in

sagittal sinus. Thus the CSF turns over about 3.7

the form of a mRNA (messenger RNA) strand that holds

times a day. This continuous flow into the venous

information about creating a protein from a gene. Every

system

larger,

amino acid has a specific three letter corresponding code

lipoinsoluble molecules penetrating the brain and

(called a codon) in the DNA sequence. You will have to

dilutes

the

concentration

of

refer to a codon chart to know the code for every amino

CSF.[5]

acid. In such charts, amino acid abbreviations are generally


The CSF

contains

proteins,

or

approximately

approximately

15

0.3%
to

plasma

used.

40 mg/dL,

depending on sampling site.[4] CSF pressure ranges

This mRNA code has a sequence of codons which provides

from 80 to 100 mmH2O (780980 Pa or 4.4

the order of assembling various amino acids together. From

7.3 mmHg)

200 mmH20

the strand of mRNA transported in the cytoplasm, tRNA

(1.94 kPa) in normal children and adults, with most

(transfer RNA) carry the information about the amino acid

variations due to coughing or internal compression

sequence to a ribosome site for protein assembly. So the

of jugular veins in the neck.

order of an amino acid sequence, if known, can be used to

There

in

are

newborns,

quantitative

and

<

differences

in

the

distributions of a number of proteins in the CSF. In

decipher the corresponding DNA code segment or gene


that created it through reverse engineering!

general, globular proteins and albumin are in lower


concentration

in

ventricular

CSF

compared

to

lumbar or cisternal fluid

FUNGSI PROTEIN
Sebagai yang terentang di dalam membrane membentuk
jalur atau saluran berisi air yang menembus lipid lapisan

What is an Amino Acid Sequence?

ganda sehingga memungkinkan zat-zat larut air yang cukup

An amino acid sequence, as you might already guessed, is

kecil memasuki saluran, misalnya ion.

the order in which various amino acids get linked to form a

Setiap saluran dapat terbuka atau tertutup terhadap ion

protein or peptide chains. A peptide chain is a long

spesifiknya akibat perubahan bentuk saluran sebagai

covalently bonded chain of amino acids. If a peptide chain,

respon terhadap mekanisme pengontrol.

happens to be a protein, its amino acid sequence

Sebagai molekul pembawa yang mengangkut zat-zat yang

alignment is called the 'Primary Structure' of that protein.

tidak mampu menembus membrane dengan sendirinya.

Branched chain amino acids form all the proteins of the

Dengan demikian saluran dan molekul pembawa keduanya

human body.

penting dalam transportasi zat-zat antara CES dan CIS.


Contoh: Hemoglobin sebagai transport oksigen dalam

Proteins and peptide chains are created through the

darah, seruloplasmin sebagai transport tembaga dalam

formation of peptide bonds between different amino acids.

darah.

The amino acid sequence is created through the bonding of

Banyak protein di luar permukaan berfungsi sebagai

the carboxyl group of one amino acid with the amino group

tempat reseptor yang mengenali dan berikatan dengan

of another. This kind of linking goes on until polypeptides

molekul-molekul

spesifik

di

lingkungan

sekitar

sel

pengikatan

ini

mencetus

serangkaian

kejadian

standard amino acids; however, in certain organisms the

dipermukaan membrane dan di dalam sel yang mengubah

genetic code can include selenocysteineand in certain

aktivitas sel tertentu.

Kelompok protein lain berfungsi sebagai enzim yang terikat

after

or

even

during

synthesis, the residues in a protein are often chemically

dipermukaan dalam atau luar sel. Sel-sel memperlihatkan

modified by post-translational modification, which alters the

menbran plasma.

Shortly

ke membrane yang mengontrol reaksi-reaksi kimia tertentu


khususnya pada jenis enzim yang terbenam dalam

archaeapyrrolysine.

physical and chemical properties, folding, stability, activity,

Contoh glikolat oksidasi dari glioksisom, dan alkahol

and ultimately, the function of the proteins. Proteins can

dehidrogenase pada fermentasi alcohol.

also work together to achieve a particular function, and they

Sebagian protein tersusun dalam sualu jalinan filamentosa

often associate to form stable complexes.

dipermukaan bagian dalam membrane dan dihubungkan

dengan unsur-unsur protein tertentu pada sitoskleton.

Of the most distinguishing features of polypeptides is their

Protein lain berfungsi sebagai molekul adhesi sel. Molekul-

ability to fold into a globual state, or "structure". The extent

molekul ini menonjol keluar dari permukaan membrane

to which proteins fold into a defined structure varies widely.

dan membentuk lengkungan-lengkungan atau anggota


badan laju yang digunakan oleh sel untuk saling

berpegangan dan untuk melekatkan ke serat-serat jaringan

rigid structure with small fluctuations and are therefore

ikat yang menjalin antara sel-sel.

considered to be single structure. Other proteins have been

Contoh: kolagen jaringan ikat fibrora (kartilago, tulang,


tendon), myosin, aktin.

to

undergo

large

rearrangements

from

one

conformation to another. This conformational change is

penting untuk kemampuan sel mengenali diri dan dalam

often associated with a signaling event. Thus, the structure

interaksi sel ke sel.

of a protein serves as a medium through which to regulate

Selain itu protei juga berfungsi sebagai aktivitas hormonal,


hormone

pertumbuhan

yang

mengatur

either the function of a protein or activity of an enzyme. Not

pertumbuhan tulang, dan juga pada saat kita digigit ular

all proteins requiring a folding process in order to function

tubuh akan mengeluarkan enzim hidrolitik (degra dastis).

as some function in an unfolded state.

Sebagian protein berfungsi sebagai toksin seperti toksin


glistridium botulinun yakni tiksin makanan bacterial letal.

shown

Protein lain khususnya bersama dengan karbohidrat

seperti

Data supports that some protein structures fold into a highly

Like

other

biological

macromolecules

such

as

Ada juga protein yang berungsi sebagai proteksi seperti

polysaccharides and nucleic acids, proteins are essential

antibody yang berinteraksi dengan proein asing, fibrinogen

parts of organisms and participate in virtually every process

yang digunakan dalam pembekuan darah, juga insulin


sebgai regulator metabolism glukosa dalam darah.

within cells. Many proteins are enzymes that catalyze

Dan juga ada sebagian protein yangberfungsi sebagai

biochemical reactions and are vital to metabolism. Proteins

cadangan dalam tubuh, seperti fertin sebagai cadagan zat

also have structural or mechanical functions, such as actin

besi (limpa) dan juga kasein cadangan asam amino

and myosin in muscle and the proteins in the cytoskeleton,

Protein
Proteins (also known as polypeptides) are organic
compounds made of amino acids arranged in a linear chain
and folded into a globular form. The amino acids in a
polymer are joined together by the peptide bonds between
the carboxyl and amino groups of adjacent amino acid
residues. The sequence of amino acids in a protein is
defined by the sequence of a gene, which is encoded in the
genetic code. In general, the genetic code specifies 20

which form a system of scaffolding that maintains cell


shape. Other proteins are important in cell signaling,
immune responses, cell adhesion, and the cell cycle.
Proteins are also necessary in animals' diets, since animals
cannot synthesize all the amino acids they need and must
obtain essential amino acids from food. Through the
process of digestion, animals break down ingested protein
into free amino acids that are then used in metabolism.
Synthesis

The DNA sequence of a gene encodes the amino acid

number of amino acids it contains and by its total molecular

sequence of a protein.

mass, which is normally reported in units of daltons

Proteins are assembled from amino acids using information

(synonymous with atomic mass units), or the derivative unit

encoded in genes. Each protein has its own unique amino

kilodalton (kDa). Yeast proteins are on average 466 amino

acid sequence that is specified by the nucleotide sequence

acids long and 53 kDa in mass.[11] The largest known

of the gene encoding this protein. The genetic code is a set

proteins are the titins, a component of the muscle

of three-nucleotide sets called codons and each three-

sarcomere, with a molecular mass of almost 3,000 kDa and

nucleotide combination designates an amino acid, for

a total length of almost 27,000 amino acids.

example AUG (adenine-uracil-guanine) is the code for


methionine. Because DNA contains four nucleotides, the
total number of possible codons is 64; hence, there is some
redundancy in the genetic code, with some amino acids
specified by more than one codon.[12] Genes encoded in
DNA are first transcribed into pre-messenger RNA (mRNA)
by proteins such as RNA polymerase. Most organisms then
process the pre-mRNA (also known as a primary transcript)
using various forms of post-transcriptional modification to
form the mature mRNA, which is then used as a template
for protein synthesis by the ribosome. In prokaryotes the
mRNA may either be used as soon as it is produced, or be
bound by a ribosome after having moved away from the
nucleoid. In contrast, eukaryotes make mRNA in the cell
nucleus and then translocate it across the nuclear
membrane into the cytoplasm, where protein synthesis then
takes place. The rate of protein synthesis is higher in
prokaryotes than eukaryotes and can reach up to 20 amino
acids per second.

Chemical synthesis
Short proteins can also be synthesized chemically by a
family of methods known as peptide synthesis, which rely
on organic synthesis techniques such as chemical ligation
to produce peptides in high yield.[15] Chemical synthesis
allows for the introduction of non-natural amino acids into
polypeptide chains, such as attachment of fluorescent
probes to amino acid side chains. These methods are
useful in laboratory biochemistry and cell biology, though
generally not for commercial applications. Chemical
synthesis is inefficient for polypeptides longer than about
300 amino acids, and the synthesized proteins may not
readily assume their native tertiary structure. Most chemical
synthesis methods proceed from C-terminus to N-terminus,
opposite the biological reaction.
Structure of proteins
Three possible representations of the three-dimensional
structure of the protein triose phosphate isomerase. Left:

The process of synthesizing a protein from an mRNA

all-atom representation colored by atom type. Middle:

template is known as translation. The mRNA is loaded onto

Simplified

the ribosome and is read three nucleotides at a time by

conformation, colored by secondary structure. Right:

matching each codon to its base pairing anticodon located

Solvent-accessible

on a transfer RNA molecule, which carries the amino acid

residue type (acidic residues red, basic residues blue, polar

corresponding to the codon it recognizes. The enzyme

residues green, nonpolar residues white).

aminoacyl tRNA synthetase "charges" the tRNA molecules

Most proteins fold into unique 3-dimensional structures.

with the correct amino acids. The growing polypeptide is

The shape into which a protein naturally folds is known as

often termed the nascent chain. Proteins are always

its native conformation. Although many proteins can fold

biosynthesized from N-terminus to C-terminus.

unassisted, simply through the chemical properties of their

The size of a synthesized protein can be measured by the

amino

representation

acids,

surface

others

illustrating

the

representation

require

the

aid

backbone

colored

of

by

molecular

chaperones to fold into their native states. Biochemists

(IgG, an antibody), hemoglobin, insulin (a hormone),

often refer to four distinct aspects of a protein's structure:

adenylate kinase (an enzyme), and glutamine synthetase

Primary structure: the amino acid sequence.

Secondary structure: regularly repeating local structures


stabilized by hydrogen bonds. The most common examples
are the alpha helix, beta sheet and turns. Because
secondary structures are local, many regions of different
secondary structure can be present in the same protein
molecule.

Tertiary structure: the overall shape of a single protein


molecule; the spatial relationship of the secondary
structures to one another. Tertiary structure is generally

Proteins can be informally divided into three main classes,


which correlate with typical tertiary structures: globular
proteins, fibrous proteins, and membrane proteins. Almost
all globular proteins are soluble and many are enzymes.
Fibrous proteins are often structural, such as collagen, the
major component of connective tissue, or keratin, the
protein component of hair and nails. Membrane proteins
often serve as receptors or provide channels for polar or
charged molecules to pass through the cell membrane.

stabilized by nonlocal interactions, most commonly the

A special case of intramolecular hydrogen bonds within

formation of a hydrophobic core, but also through salt

proteins, poorly shielded from water attack and hence

bridges, hydrogen bonds, disulfide bonds, and even post-

promoting their own dehydration, are called dehydrons.

translational modifications. The term "tertiary structure" is

Structure determination

often used as synonymous with the term fold. The tertiary


structure is what controls the basic function of the protein.

(an enzyme).

Quaternary structure: the structure formed by several


protein molecules (polypeptide chains), usually called
protein subunits in this context, which function as a single
protein complex.
Proteins are not entirely rigid molecules. In addition to
these levels of structure, proteins may shift between several
related structures while they perform their functions. In the
context of these functional rearrangements, these tertiary
or quaternary structures are usually referred to as
"conformations", and transitions between them are called
conformational changes. Such changes are often induced
by the binding of a substrate molecule to an enzyme's
active site, or the physical region of the protein that
participates in chemical catalysis. In solution proteins also
undergo variation in structure through thermal vibration and
the collision with other molecules.

Discovering the tertiary structure of a protein, or the


quaternary

structure

of its complexes,

can provide

important clues about how the protein performs its function.


Common experimental methods of structure determination
include X-ray crystallography and NMR spectroscopy, both
of which can produce information at atomic resolution.
However, NMR experiments are able to provide information
from which a subset of distances between pairs of atoms
can be estimated, and the final possible conformations for a
protein are determined by solving a distance geometry
problem. Dual polarisation interferometry is a quantitative
analytical method for measuring the overall protein
conformation

and

conformational

changes

due

to

interactions or other stimulus. Circular dichroism is another


laboratory technique for determining internal beta sheet/
helical composition of proteins. Cryoelectron microscopy is
used to produce lower-resolution structural information
about very large protein complexes, including assembled
viruses;[24] a variant known as electron crystallography
can also produce high-resolution information in some cases

Molecular surface of several proteins showing their

, especially for two-dimensional crystals of membrane

comparative sizes. From left to right are: immunoglobulin G

proteins.[25] Solved structures are usually deposited in the

Protein Data Bank (PDB), a freely available resource from

responsible for binding another molecule is known as the

which structural data about thousands of proteins can be

binding site and is often a depression or "pocket" on the

obtained in the form of Cartesian coordinates for each atom

molecular surface. This binding ability is mediated by the

in the protein.[26]

tertiary structure of the protein, which defines the binding

Many more gene sequences are known than protein


structures. Further, the set of solved structures is biased
toward proteins that can be easily subjected to the
conditions required in X-ray crystallography, one of the
major structure determination methods. In particular,
globular proteins are comparatively easy to crystallize in
preparation for X-ray crystallography. Membrane proteins,
by

contrast,

are

difficult

to

crystallize

and

are

underrepresented in the PDB.[27] Structural genomics


initiatives have attempted to remedy these deficiencies by
systematically solving representative structures of major
fold classes. Protein structure prediction methods attempt

site pocket, and by the chemical properties of the


surrounding amino acids' side chains. Protein binding can
be extraordinarily tight and specific; for example, the
ribonuclease inhibitor protein binds to human angiogenin
with a sub-femtomolar dissociation constant (<1015 M) but
does not bind at all to its amphibian homolog onconase (>1
M). Extremely minor chemical changes such as the addition
of a single methyl group to a binding partner can
sometimes suffice to nearly eliminate binding; for example,
the aminoacyl tRNA synthetase specific to the amino acid
valine discriminates against the very similar side chain of
the amino acid isoleucine.

to provide a means of generating a plausible structure for

Proteins can bind to other proteins as well as to small-

proteins whose structures have not been experimentally

molecule substrates. When proteins bind specifically to

determined.

other copies of the same molecule, they can oligomerize to


form fibrils; this process occurs often in structural proteins

Cellular functions

that consist of globular monomers that self-associate to


Proteins are the chief actors within the cell, said to be

form rigid fibers. Proteinprotein interactions also regulate

carrying out the duties specified by the information encoded

enzymatic activity, control progression through the cell

in genes. With the exception of certain types of RNA, most

cycle, and allow the assembly of large protein complexes

other biological molecules are relatively inert elements

that carry out many closely related reactions with a

upon which proteins act. Proteins make up half the dry

common biological function. Proteins can also bind to, or

weight

other

even be integrated into, cell membranes. The ability of

macromolecules such as DNA and RNA make up only 3%

binding partners to induce conformational changes in

and 20%, respectively. The set of proteins expressed in a

proteins allows the construction of enormously complex

particular cell or cell type is known as its proteome.

signaling networks.[30] Importantly, as interactions between

of

an

Escherichia

coli

cell,

whereas

proteins are reversible, and depend heavily on the


availability of different groups of partner proteins to form
The enzyme hexokinase is shown as a simple ball-and-

aggregates that are capable to carry out discrete sets of

stick molecular model. To scale in the top right-hand corner

function, study of the interactions between specific proteins

are two of its substrates, ATP and glucose.

is a key to understand important aspects of cellular

The chief characteristic of proteins that also allows their

function, and ultimately the properties that distinguish

diverse set of functions is their ability to bind other

particular cell types.[31][32]

molecules specifically and tightly. The region of the protein

Enzymes

The best-known role of proteins in the cell is as enzymes,

system whose main function is to bind antigens, or foreign

which catalyze chemical reactions. Enzymes are usually

substances in the body, and target them for destruction.

highly specific and accelerate only one or a few chemical

Antibodies

reactions. Enzymes carry out most of the reactions involved

environment or anchored in the membranes of specialized

in metabolism, as well as manipulating DNA in processes

B cells known as plasma cells. Whereas enzymes are

such as DNA replication, DNA repair, and transcription.

limited in their binding affinity for their substrates by the

Some enzymes act on other proteins to add or remove

necessity of conducting their reaction, antibodies have no

chemical groups in a process known as post-translational

such constraints. An antibody's binding affinity to its target

modification. About 4,000 reactions are known to be

is extraordinarily high.

catalyzed by enzymes. The rate acceleration conferred by


enzymatic catalysis is often enormous as much as 10 17fold increase in rate over the uncatalyzed reaction in the
case of orotate decarboxylase (78 million years without the
enzyme, 18 milliseconds with the enzyme).

can

be

secreted

into

the

extracellular

Many ligand transport proteins bind particular small


biomolecules and transport them to other locations in the
body of a multicellular organism. These proteins must have
a high binding affinity when their ligand is present in high
concentrations, but must also release the ligand when it is

The molecules bound and acted upon by enzymes are

present at low concentrations in the target tissues. The

called substrates. Although enzymes can consist of

canonical

hundreds of amino acids, it is usually only a small fraction

haemoglobin, which transports oxygen from the lungs to

of the residues that come in contact with the substrate, and

other organs and tissues in all vertebrates and has close

an even smaller fraction 3 to 4 residues on average

homologs in every biological kingdom.[38] Lectins are

that are directly involved in catalysis.[35] The region of the

sugar-binding proteins which are highly specific for their

enzyme that binds the substrate and contains the catalytic

sugar moieties. Lectins typically play a role in biological

residues is known as the active site.

recognition phenomena involving cells and proteins.[39]

Cell signaling and ligand binding

example

of

ligand-binding

protein

is

Receptors and hormones are highly specific binding


proteins.

Ribbon diagram of a mouse antibody against cholera that


binds a carbohydrate antigen
Many proteins are involved in the process of cell signaling
and signal transduction. Some proteins, such as insulin, are
extracellular proteins that transmit a signal from the cell in
which they were synthesized to other cells in distant
tissues. Others are membrane proteins that act as
receptors whose main function is to bind a signaling
molecule and induce a biochemical response in the cell.
Many receptors have a binding site exposed on the cell
surface and an effector domain within the cell, which may
have enzymatic activity or may undergo a conformational
change detected by other proteins within the cell.[36]
Antibodies are protein components of adaptive immune

Transmembrane proteins can also serve as ligand transport


proteins that alter the permeability of the cell membrane to
small molecules and ions. The membrane alone has a
hydrophobic

core

through

which

polar

or

charged

molecules cannot diffuse. Membrane proteins contain


internal channels that allow such molecules to enter and
exit the cell. Many ion channel proteins are specialized to
select for only a particular ion; for example, potassium and
sodium channels often discriminate for only one of the two
ions.[40]
Structural proteins
Structural proteins confer stiffness and rigidity to otherwisefluid biological components. Most structural proteins are
fibrous proteins; for example, actin and tubulin are globular

and soluble as monomers, but polymerize to form long, stiff

animals had entered the human food chain before controls

fibers that comprise the cytoskeleton, which allows the cell

on high-risk offal were introduced in 1989.

to maintain its shape and size. Collagen and elastin are


critical components of connective tissue such as cartilage,
and keratin is found in hard or filamentous structures such
as hair, nails, feathers, hooves, and some animal shells.

A British inquiry into BSE concluded that the epizootic was


caused by cattle, who are normally herbivores, being fed
the remains of other cattle in the form of meat and bone
meal (MBM), which caused the infectious agent to spread.

Other proteins that serve structural functions are motor

The origin of the disease itself remains unknown. The

proteins such as myosin, kinesin, and dynein, which are

infectious agent is distinctive for the high temperatures at

capable of generating mechanical forces. These proteins

which it remains viable; this contributed to the spread of the

are crucial for cellular motility of single celled organisms

disease in Britain, which had reduced the temperatures

and the sperm of many multicellular organisms which

used during its rendering process. Another contributory

reproduce sexually. They also generate the forces exerted

factor was the feeding of infected protein supplements to

by contracting muscles.

very young calves.

Bovine spongiform encephalopathy

Cause

Classic image of a cow with BSE. A feature of such disease

Microscopic "holes" of tissue sections are examined in the

is the inability of the infected animal to stand.

lab. Source: APHIS

Bovine spongiform encephalopathy (BSE), commonly

The infectious agent in BSE is believed to be a specific

known as mad-cow disease, is a fatal, neurodegenerative

type of misfolded protein called a prion. Prion proteins carry

disease in cattle, that causes a spongy degeneration in the

the disease between individuals and cause deterioration of

brain and spinal cord. BSE has a long incubation period,

the brain. BSE is a type of transmissible spongiform

about 4 years, usually affecting adult cattle at a peak age

encephalopathy (TSE).[12] TSEs can arise in animals that

onset of four to five years, all breeds being equally

carry an allele which causes previously normal protein

susceptible. In the United Kingdom, the country worst

molecules to contort by themselves from an alpha helical

affected, more than 179,000 cattle have been infected and

arrangement to a beta pleated sheet, which is the disease-

4.4 million slaughtered during the eradication program.

causing shape for the particular protein. Transmission can

The disease may be most easily transmitted to human


beings by eating food contaminated with the brain or spinal
cord of infected carcasses. However, it should also be
noted that the infectious agent, although most highly
concentrated in nervous tissue, can be found in virtually all
tissues throughout the body, including blood. In humans, it
is known as new variant CreutzfeldtJakob disease (vCJD
or nvCJD), and by October 2009, it had killed 166 people in
Britain (the most recent being of a different genotype than

occur when healthy animals come in contact with tainted


tissues from others with the disease. In the brain these
proteins cause native cellular prion protein to deform into
the infectious state, which then goes on to deform further
prion protein in an exponential cascade. This results in
protein aggregates, which then form dense plaque fibers,
leading to the microscopic appearance of "holes" in the
brain, degeneration of physical and mental abilities, and
ultimately death.

other sufferers), and 44 elsewhere with the number

Different hypotheses exist for the origin of prion proteins in

expected to rise because of the disease's long incubation

cattle. Two leading hypotheses suggest that it may have

period. Between 460,000 and 482,000 BSE-infected

jumped species from the disease scrapie in sheep, or that it

evolved from a spontaneous form of "mad cow disease"

increase of the infectious agents in the cattle feed. A

that has been seen occasionally in cattle for many

contributing factor was suggested to have been a change in

centuries. Publius Flavius Vegetius Renatus records cases

British laws that allowed a lower temperature sterilization of

of a disease with similar characteristics in the 4th and 5th

the protein meal. While other European countries like

century AD. The British Government enquiry took the view

Germany required said animal byproducts to undergo a

the cause was not scrapie as had originally been

high temperature steam boiling process, this requirement

postulated, and was some event in the 1970s that it was

had been eased in Britain as a measure to keep prices

not possible to identify.

competitive. Later the British Inquiry dismissed this theory

Findings published in PLoS Pathogens (September 12,


2008) suggest that mad cow disease also is caused by a
genetic mutation within a gene called Prion Protein Gene.

saying "changes in process could not have been solely


responsible for the emergence of BSE, and changes in
regulation were not a factor at all."

The research shows, for the first time, that a 10-year-old

The first animal to fall ill with the disease occurred in 1984

cow from Alabama with an atypical form of bovine

in Britain, lab tests the following year indicated the

spongiform encephalopathy had the same type of prion

presence of BSE; it was only in November 1986 that the

protein gene mutation as found in human patients with the

British Ministry of Agriculture accepted it had a new disease

genetic form of CreutzfeldtJakob disease, also called

on its hands. Subsequently, 165 people (up until October

genetic CJD for short. Besides having a genetic origin,

2009) acquired and died of a disease with similar

other human forms of prion diseases can be sporadic, as in

neurological symptoms subsequently called vCJD, or (new)

sporadic CJD, as well as foodborne. That is, they are

variant Creutzfeldt-Jakob disease. This is a separate

contracted when people eat products contaminated with

disease from 'classical' CreutzfeldtJakob disease, which is

mad cow disease. This form of Creutzfeldt-Jakob disease is

not related to BSE and has been known about since the

called variant CJD.

early 1900s. Three cases of vCJD occurred in people who

Epidemic in British cattle

had lived in or visited Britain one each in Ireland,


Canada and the United States. There is also some concern

Cattle are normally herbivores. In nature, cattle eat grass.

about those who work with (and therefore inhale) cattle

In modern industrial cattle-farming, various commercial

meat and bone meal, such as horticulturists, who use it as

feeds are used, which may contain ingredients including

fertilizer. Up to date statistics on all types of CJD are

antibiotics, hormones, pesticides, fertilizers, and protein

published by the National Creutzfeldt-Jakob Disease

supplements. The use of meat and bone meal, produced

Surveillance Unit (NCJDSU) in Edinburgh.

from the ground and cooked left-overs of the slaughtering


process as well as from the cadavers of sick and injured
animals such as cattle, sheep, or chickens, as a protein
supplement in cattle feed was widespread in Europe prior
to about 1987. Worldwide, soya bean meal is the primary
plant-based protein supplement fed to cattle. However,
soya beans do not grow well in Europe, so cattle raisers
throughout Europe turned to the less expensive animal byproduct feeds as an alternative. A change to the rendering
process in the early 1980s may have resulted in a large

For many of the vCJD patients, direct evidence exists that


they had consumed tainted beef, and this is assumed to be
the mechanism by which all affected individuals contracted
it. Disease incidence also appears to correlate with
slaughtering practices that led to the mixture of nervous
system tissue with hamburger and other beef. It is
estimated that 400,000 cattle infected with BSE entered the
human food chain in the 1980s. Although the BSE epizootic
was eventually brought under control by culling all suspect

cattle populations, people are still being diagnosed with

memperlihatkan setidaknya 2 konformasi yang stabil.

vCJD each year (though the number of new cases currently

Konformasi dalam keadaan asli itu larut air dan ada dalam

has dropped to fewer than 5 per year). This is attributed to

sel yang sehat. Sampai 2006, fungsi biologisnya tak

the long incubation period for prion diseases, which are

diketahui. Keadaan konformatif lainnya kurang larut air dan

typically measured in years or decades. As a result the

mudah membentuk agregat protein.

extent of the human vCJD outbreak is still not fully known.

Orang juga bisa terjangkit Creutzfeldt-Jakob melalui mutasi

The scientific consensus is that infectious BSE prion

gen (perlu didefinisikan), yang hanya terjadi dalam 5-10%

material

dari semua kasus.

is

not

destroyed

through

normal

cooking

procedures, meaning that contaminated beef foodstuffs


prepared "well done" may remain infectious.

Prion Creutzfeldt-Jakob berbahaya karena meningkatkan


pelipatan protein asal ke dalam keadaan sakit, yang

In 2004 researchers reported evidence of a second

menyebabkan meningkatnya prion tak larut pada sel yang

contorted shape of prions in a rare minority of diseased

terjangkit. Massa protein yang salah lipat ini mengacaukan

cattle. If valid, this would imply a second strain of BSE

fungsi sel dan menyebabkan kematiannya. Mutasi pada

prion. Very little is known about the shape of disease-

gen untuk protein prion bisa menyebabkan kesalahan lipat

causing prions, because their insolubility and tendency to

sebagian besar regio alfa-heliks ke lembar beta yang

clump thwarts application of the detailed measurement

terlipat.

techniques of structural biology. But cruder measures yield

kemampuan protein mengalami pencernaan. Sekali prion

a "biochemical signature" by which the newly discovered

ditransmisikan, protein cacat itu menyerang otak dan

cattle strain appears different from the familiar one, but

diproduksi di putaran umpan balik yang disokong sendiri,

similar to the clumped prions in humans with traditional

menyebabkan penyebaran eksponensial prion, kematian

CJD Creutzfeldt-Jakob Disease. The finding of a second

dalam beberapa bulan, meski beberapa orang diketahui

strain of BSE prion raises the possibility that transmission

hidup selama-lamanya 2 tahun.

of BSE to humans has been underestimated, because

Perubahan

konformasi

ini

melumpuhkan

Insidensi dan prevalensi

some of the individuals diagnosed with spontaneous or


"sporadic" CJD may have actually contracted the disease

Meski merupakan penyakit prion yang paling umum pada

from tainted beef. So far nothing is known about the relative

manusia, Creutzfeldt-Jakob masih jarang dan hanya terjadi

transmissibility of the two disease strains of BSE prion.

pada sekitar 1:1.000.000 orang, yang biasanya menjangkiti

Penyakit Creutzfeldt-Jakob
Penyebab
Penyakit ensefalopati spongiform menular ini disebabkan

orang antara usia 4575, kebanyakan muncul pada orang


antara usia 6065. Pengecualian dalam hal ini adalah
Creutzfeldt-Jakob varian (vCJD) yang kini dikenali, yang
terjadi pada orang berusia muda.

oleh prion, sehingga sering disebut sebagai penyakit prion.

Creutzfeldt-Jakob terjadi sedunia dalam tingkat 1:1.000.000

Penyakit prion lainnya termasuk Sindrom Gerstmann-

penduduk per tahun.

Strussler-Scheinker (GSS), insomnia familial fatal dan

Penyakit ini paling banyak ditemukan pada pasien antara

kuru pada manusia, juga ensefalopati spongiform sapi yang

usia 5565, namun kasus ini dapat terjadi pada orang yang

umum dikenal sebagai penyakit sapi gila, chronic wasting

berusia lebih dari 90 tahun dan kurang dari 55 tahun.

disease (CWD) pada rusa, dan scrapie pada domba.

Gejala

Prion yang dipercaya menyebabkan Creutzfeldt-Jakob

Gejala pertama Creutzfeldt-Jakob adalah demensia yang

cepat dengan mioklonus. Pengamatan lanjutan kemudian

berlangsung cepat, menimbulkan kehilangan ingatan,

dapat dilakukan untuk mendukung diagnosis termasuk

perubahan kepribadian dan halusinasi, yang disertai


dengan masalah fisik seperti menurunnya kecakapan
berbicara, gerakan tertegun-tegun (mioklonus), disfungsi
keseimbangan

koordinasi

(ataksia),

perubahan

gaya

berjalan, postur yang kaku, dan serangan jantung. Durasi


penyakit ini bervariasi, namun Creutzfeldt-Jakob yang
sporadik (tak diwarisi) bisa fatal dalam beberapa bulan
bahkan minggu (Johnson, 1998). Pada beberapa orang,
gejala itu bisa berlanjut selama beberapa tahun. Pada
sebagian besar pasien, gejala tersebut diikuti dengan
gerakan

tak

sadar

dan

munculnya

pelacakan

elektroensefalogram diagnostik khas.


Gejala Creutzfeldt-Jakob disebabkan oleh kematian sel
saraf otak yang berkelanjutan, yang dikaitkan dengan
bertambahnya protein prion abnormal. Saat jaringan otak
penderita Creutzfeldt-Jakob diperiksa di bawah mikroskop,
banyak lubang kecil terlihat di mana keseluruhan area sel
saraf mati. Kata 'spongiform' pada 'ensefalopati spongiform
menular' merujuk pada kemunculan 'pori' pada jaringan
otak.
Diagnosis
Diagnosis Creutzfeldt-Jakob dicurigai bila ada gejala klinik
dan tanda yang khas seperti demensia yang berlangsung

Usia kematian rata-rata


Durasi sakit rata-rata

Elektroensefalografi sering ada gambaran paku trifasik


yang khas
Analisis cairan serebrospinal untuk protein 14-3-3
MRI otak sering menunjukkan intensitas sinyal tinggi di
nucleus caudatus dan putamen secara bilateral pada
gambar diapit T2.
Gambar Diffusion Weighted Imaging (DWI) paling sensitif.
24% kasus DWI hanya menunjukkan hiperintensitas
korteks; 68% abnormalitas korteks dan subkorteks; dan 5%
hanya anomali subkorteks Keterlibatan talamus dapat
ditemukan

Analisis imunohistokimia jaringan otak


Keberadaan agen di jaringan getah bening
Pertambahan rasio glikoform pada analisis imunoblot protein
prion resisten protease

sCJD

(Creutzfeldt-Jakob

sporadik),

malahan lebih kuat dan konstan daripada vCJD.


Dalam sepertiga pasien sCJD, endapan "protein prion
(scrapie)," PrPSc, dapat ditemukan di otot rangka dan/atau
limpa. Diagnosis vCJD dapat didukung dengan biopsi
amandel, yang mengandung PrpSc dalam jumlah banyak;
namun, biopsi jaringan otak lebih bersifat menentukan.
Penularan
Protein yang cacat dapat ditularkan oleh produk hormon
pertumbuhan

manusia

(hGH),

cangkoqan

kornea,

cangkoqan dura atau implan elektrode (bentuk yang


didapat atau iatrogenik: iCJD); dapat diwarisi (bentuk
herediter atau familial: fCJD); atau muncul untuk pertama
CJD klasik
68 tahun
4-5bulan
Demensia;
tanda
neurologis awal

Tanda dan gejala klinik

Gelombang elekteroensefalogram yang tajam secara berkala


Hiperintensitas sinyal di nucleus caudatus dan putamen pada
difusi apit dan FLAIR MRI
"Tanda pulvinar" di MRI

pada

Sering ada
Sering ada
Tak dilaporkan
Akumulasi
bervariasi
Tak
mudah
dideteksi
Tak dilaporkan

CJD varian
28tahun
13-14bulan
Gejala psikiatri/perilaku
mencolok; disestesias
nyeri;
Tanda neurologis yang
terlambat
Sering tiada
Sering tiada
Ada dalam >75% kasus
Akumulasi protein prion
resisten protease
yang mengancam
Mudah dideteksi
Akumulasi protein prion
resisten protease
yang mengancam

kalinya

pada

pasien (bentuk
sporadik:
sCJD).

Dalam

bentuk
herediter,
sebuah mutasi
terjadi

pada

gen untuk PrP,


PRNP. 10-15%
kasus
Creutzfeldt-

Jakob diwarisi. (CDC)

tahun 1985.

Penyakit itu telah diketahui diakibatkan dari penggunaan

Diperkirakan manusia dapat terjangkit penyakit ini dengan

HGH yang diambil dari kelenjar pituitari kadaver yang mati

mengkonsumsi bahan dari hewan yang terinfeksi penyakit

akibat penyakit Creutzfeldt-Jakob,[14] meski insidensi

ini yang dari jenis sapi. Sejauh ini, satu-satunya kasus yang

penyebabnya yang diketahui cukup kecil (sampai April

dicurigai muncul adalah vCJD.

2004). Risiko infeksi melalui penggunaan HGH kadaver di


AS hanya berakhir saat pengobatan itu dihentikan pada

Dapat juga ditularkan melalui transfusi darah.

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