DRUG - RECEPTOR

KULIAH 3

ENZYME- RECEPTOR
Enzyme: A protein (or protein-based
molecule) that speeds up a chemical
reaction in a living organism.
An enzyme acts as catalyst for specific
chemical reactions, converting a
specific set of reactants (called
substrates) into specific products.
Without enzymes, life as we know it
would not exist.

 enzyme : Symbol E
a protein that catalyzes chemical reactions of
other substances without itself being
destroyed or altered upon completion of the
reactions.
Enzymes are divided into six main groups,
according to the reactions they catalyze :
oxidoreductases,
transferases,
hydrolases,
lyases,
isomerases, and
ligases.

 llosteric enzyme one whose catalytic activity is

altered by binding of specific ligands at sites other
than the substrate binding site.
brancher enzyme, branching enzyme 1,4-glucan branching enzyme: an enzyme that
catalyzes the creation of branch points in glycogen
(in plants, amylopectin); deficiency causes
glycogen storage disease type IV.
constitutive enzyme one produced constantly,
irrespective of environmental conditions or
demand.
debrancher enzyme, debranching enzyme
1. amylo-1,6-glucosidase.
2. any enzyme removing branches from
macromolecules, usually polysaccharides, by
cleaving at branch points.

 induced enzyme, inducible enzyme

one whose production can be stimulated
by another compound, often a substrate
or a structurally related molecule.
proteolytic enzyme peptidase.
repressible enzyme one whose rate of
production is decreased as the
concentration of certain metabolites is
increased.
respiratory enzyme one that is part of
an electron transport (respiratory) chain.

Enzyme Composition
Enzymes can have molecular weights ranging
from about 10,000 to over 1 million. A small
number of enzymes are not proteins, but consist
of small catalytic RNA molecules.
Often, enzymes are multiprotein complexes
made up of a number of individual protein
subunits.
Many enzymes catalyze reactions without help,
but some require an additional non-protein
component called a co-factor. Co-factors may be
inorganic ions such as Fe2+, Mg2+, Mn2+, or Zn2+,
or consist of organic or metalloorganic
molecules knowns as co-enzymes.

 Alcohol dehydrogenase: an oxidoreductase

converting alcohols to aldehydes/ ketones.
Aminotransferases: transferases catalyzing the
amino acid degradation by removing amino groups.
Glucose-6-phosphatase: a hydrolase that removes
the phosphate group from glucose-6-phosphate,
leaving glucose and H3PO4.
Pyruvate decarboxylase: a lyase that removes CO 2
from pyruvate.
Ribulose phosphate epimerase: an isomerase that
catalyzes the interconversion of ribulose-5phosphate and xylulose-5-phosphate.
Hexokinase: a ligase that catalyzes the
interconversion of glucose and ATP with glucose-6phosphate and ADP.

Asam nukleat
Nucleic acid structure refers to the
structure of nucleic acids such as
DNA and RNA It is often divided into
four different levels:
Struktur primer
S. sekunder
S tersier
S. Kuarterner

 Nucleic acids consist of a chain of linked

units called nucleotides.
Each nucleotide consists of three
subunits: a phosphate group and a sugar
(ribose in the case of RNA, deoxyribose
in DNA) make up the backbone of the
nucleic acid strand, and attached to the
sugar is one of a set of nucleobases.
The nucleobases are important in
base pairing of strands to form higherlevel secondary and tertiary structure
such as the famed double helix.

 RNA

Sekunder

Tersier

Kuarterner
The quaternary structure of a nucleic acid
refers to the interactions between separate nucleic
acid molecules, or
between nucleic acid molecules and proteins .
The concept is analogous to
protein quaternary structure, but as the analogy is
not perfect, the term is used to refer to a number of
different concepts in nucleic acids and is less
commonly encountered.
Quaternary structure can refer to the higher-level
organization of DNA in chromatin,[1] including its
interactions with histones.
It may also refer to the interactions between
separate RNA units in the ribosome[2][3] or
spliceosome.

Receptor in biology

In biochemistry, a receptor is a protein

molecule, embedded in either the plasma
membrane or cytoplasm of a cell, to which a
mobile signaling (or "signal") molecule may
attach.
A molecule which binds to a receptor is called a
"ligand," and may be a peptide (such as a
neurotransmitter), a hormone, a
pharmaceutical drug, or a toxin, and when such
binding occurs, the receptor goes into a
conformational change which ordinarily initiates
a cellular response.
Some ligands merely block receptors without
inducing any response (e.g. antagonists).

 In cell biology, a structure on the surface of a

cell (or inside a cell) that selectively receives
and binds a specific substance. There are many
receptors. There is a receptor for (insulin; there
is a receptor for low-density lipoproteins (LDL);
etc.
To take an example, the receptor for substance
P, a molecule that acts as a messenger for the
sensation of pain, is a unique harbor on the cell
surface where substance P docks. Without this
receptor, substance P cannot dock and cannot
deliver its message of pain.
Variant forms of nuclear hormone receptors
mediate processes such as cholesterol
metabolism and fatty acid production.

 Some hormone receptors are implicated in

diseases such as diabetes and certain
types of cancer. A receptor called PXR
appears to jump-start the body's response
to unfamiliar chemicals and may be
involved in drug-drug interactions.
In neurology, a terminal of a sensory nerve
that receives and responds to stimuli.
In Biochemistry, a molecular structure or
site on the surface or interior of a cell that
binds with substances such as hormones,
antigens, drugs, or neurotransmitters

 A structure or site, found on the surface of a cell or

within a cell, that can bind to a hormone, antigen,
or other chemical substance and thereby begin a
change in the cell.
For example, when a mast cell within the body
encounters an allergen, specialized receptors on
the mast cell bind to the allergen, resulting in the
release of histamine by the mast cell.
The histamine then binds to histamine receptors in
other cells of the body, which initiate the response
known as inflammation as well as other responses.
In this way, the symptoms of an allergic reaction
are produced.
Antihistamine drugs work by preventing the
binding of histamine to histamine receptors.

Pharmacology
A cellular macromolecule, or an assembly of
macromolecules,
that is concerned directly and specifically in
chemical signaling between and within cells.
Combination of a hormone, neurotransmitter, drug, or
intracellular
messenger with its receptor(s) initiates a change in
cell function.
Thus NC-IUPHAR does not classify simple
binding sites, without function (although truncated proteins
without signaling function may be designated as
such, to avoid confusion).

A receptor may consist of several proteins,

called subunits.
In some cases the large number of
combinatorial possibilities for assembly of
multiple subunits may require NC-IUPHAR to
use an interim nomenclature based on the
individual subunits (Spedding et al., 2002)
Receptor: Any cellular macromolecule that
a drug binds to initiate its effects.
Drug: A chemical substance that interacts
with a biological system to produce a
physiologic effect.

 All drugs are chemicals but not all

chemicals are drugs.
The ability to bind to a receptor is
mediated by the chemical structure of
the drug that allows it to interact with
complementary surfaces on the
receptor.
Drugs that interact with receptors can
be classified as being either agonists
or antagonists.
Once bound to the receptor an agonist
activates or enhances cellular activity.

 Examples of agonist action are drugs that bind to

beta receptors in the heart and increase the force
of myocardial contraction or drugs that bind to
alpha receptors on blood vessels to increase
blood pressure. The binding of the agonist often
triggers a series of biochemical events that
ultimately leads to the alteration in function.
The biochemicals that initiate these changes are
referred to as second messengers.
Antagonists have the ability to bind to the
receptor but do not initiate a change in cellular
function. Because they occupy the receptor, they
can prevent the binding and the action of
agonists. Hence the term antagonist.
Antagonists are also referred to as blockers.

INTERAKSI OBAT-RESEPTOR
Interaksi obat/drug dengan reseptor akan
menimbulkan efek biologis
Efek agonis
Efek antagonis

Mekanisme timbulnya respons ada 6 teori:

1. Teori Klasik
2. Teori kependudukan
3. Teori kecepatan
4. Teori kessuaian terimbas
5. Teori gangguan molekul
6. Teori pendudukan aktivasi

1. Teori klasik
Crum, Brown dan Fraser: 1869,
aktivitas biologis suatu senyawa
merupakan fungsi struktur kimia dan
tempat obat berinteraksi
Langley: 1878, mengungkapkan
konsep reseptor
Erlich: 1907, obat tak berefek bila tdk
tidak terikat pada reseptor yang khas,
atau sisi reseptor dan saling mengisi

2. Teori Pendudukan
Clark, 1926 : suatu obat akan menempati sisi
reseptor dan diberikan dalam jumlah banyak
agar efektif selama proses pembentukan
kompleks
O + R membentuk OR
O + R afn
Kompleks OR
efikasi
Respons
biologis
Respons (+): seny. Agonis, afn >, akt intrsik 1
Respons (-): seny. Antagonis, afn >, akt intrisik 0
Afinitas: kemampuan obat u mengikat reseptor
Aktintrisik: kemampuan obat u memulai
timbulnya respons biologis

 An agonist is a chemical that binds to a receptor

of a cell and triggers a response by that cell.
Agonists often mimic the action of a naturally
occurring substance.
Whereas an agonist causes an action, an
antagonist blocks the action of the agonist and an
inverse agonist causes an action opposite to that
of the agonist.
Receptors can be activated or inactivated by either
endogenous (such as hormones and
neurotransmitters) or exogenous (such as drugs)
agonists and antagonists, resulting in the
stimulation or inhibition of a biological response.
A physiological agonist is a substance that
creates the same bodily responses but does not
bind to the same receptor.

 An endogenous agonist for a particular receptor is a

compound naturally produced by the body that binds to
and activates that receptor.
For example, the endogenous agonist for
serotonin receptors is serotonin, and the endogenous
agonist for dopamine receptors is dopamine.[1]
Efficacy spectrum
A superagonist is a compound that is capable of
producing a greater maximal response than the
endogenous agonist for the target receptor, and thus has
an efficacy of more than 100%.
This does not necessarily mean that it is more potent
than the endogenous agonist, but is rather a comparison
of the maximum possible response that can be produced
inside the cell following receptor binding.

 Full agonists bind (have affinity for) and activate a

receptor, displaying full efficacy at that receptor. One
example of a drug that acts as a full agonist is
isoproterenol, which mimics the action of adrenaline at
adrenoreceptors.
Another example is morphine, which mimics the
actions of endorphins at -opioid receptors throughout
the central nervous system.
Partial agonists (such as buspirone, aripiprazole,
buprenorphine, or norclozapine) also bind and activate
a given receptor, but have only partial efficacy at the
receptor relative to a full agonist. One study of
benzodiazepine active sedative hypnotics found that
partial agonists have just under half the strength of full
agonists.[2] Partial agonists such as abecarnil have
demonstrated a reduced rate and reduced severity of
dependence and withdrawal syndromes.[3]
An inverse agonist is an agent that binds to the same

3. Teori kecepatan
Paton: 1961, efek biologis setara dengan
kecep kombinasi OR, bukan jumlah R yang
diduduki
Kerja obat ditentukan dgn kecepatan
asosiasi dan kecepatan disosiasi kompleks
OR bukan pembentukan OR
O + R assosiasi
dissosiasi
Respons biologis

kompleks OR

 Senyawa agonis, kecepatan assosiasi

dan disosiasi besar
Senyawa antagonis, kecepatan asosiasi
besar tp dissosiasinya kecil
Seny agonis parsial jika kecepatan
asosiasi dan dissosiasi tidak maksimal
Fakta: senyawa mempunyai efek
singkat, karena jumlah reseptor yang
diduduki sedikit, kecepatan
penggabungan maksimum, dan
rangsangan singkat

4. Teori kesesuaian terimbas

Koshland, 1955, kombinasi enzim
dan substrat akan terjadi perubahan
konformsi struktur enzim, perubahan
orientasi gugus aktif enzim
E+S

ES

Resp Bio

5. Teori gangguan molekul

Belleau, 1964, interaksi mikromolekul dan
makromolekul menyebabkan terjadi perub
konformasi reseptor:
1. Gangguan konformasi khas (SCP)
2. Gangguan konformasi tidak khas (NSCP)
Obat agonis, punya akt intrisik, mengubah
reseptor menjadi bentuk SCP
Obat antagonis, tdk punya akt intrisik,
mengubah reseptor, menjadi NSCP, efek
pemblokan,
Sbg penunjang adanya ikatan hidrofobik

6. Teori Pendudukan Aktivasi

Ariens dan Rodrigues, sebelum
berinteraksi dgn obat, eseptorr berada
dalam kesetimbangan dinamik yaitu
dalam bentuk R dan R*
R dalam bentuk istirahat, tdk dpt
menunjang efek biologis
R* bentuk yang teraktifkan, dpt
menunjang efek biologis

agonis

R R*
antagonis

 Senyawa agonis: kesetimbangan

kearah R*
Senyawa antagonis: kesetimbangan
ke arah R
Senyawa agonis parsial: terjadi
bentuk R dan R*
Senyawa agonis biasanya sangat
polar, distabilkan oleh reseptor polar
shg kesetimb kearah R* yg lebih
hiddrofil
Senyawa antagonis , memp gugus2
yang hidrofob, distabilkan oleh