Group 3

Putri Indrawati (4411415034)

Reno Yuriansyah (4411415020)
Isti Fadah (4411415050)
Nita Septiawijiastuti (4411415051)
*Enzyme inhibitors inactivate the enzyme;

*Two main types of inhibition exist:

*Reversible enzyme inhibition: enzyme activity can
be recovered by removing the inhibitor (e.g. dialysis,
gel filtration);

*Irreversible enzyme inhibition: inhibitor binds

covalently to enzyme, which is then irreversibly
inactivated.
 Reversible Inhibition

This may involve

a) competitive inhibition
b) noncompetitive inhibition
- including allosteric regulation
c) feedback inhibition
 Sometimes enzyme function can be inhibited
by other molecules (reducing the rate of
enzyme-controlled reactions)

 These molecules are called INHIBITORS

 There are COMPETITIVE INHIBITORS and

NON-COMPETITIVE INHIBITORS
 These are molecules that are similar in shape to the
substrate

 They bind to the enzyme’s active site preventing the real

substrate from binding

 The molecule “competes” with the substrate for the

active site

 This can be overcome by increasing the substrate

concentration
 substrate

Now the substrate

cannot get to the
active site because
it is blocked by the
inhibitor.

enzyme
 A molecule binds to the enzyme at a location other
than the active site

 This binding alters the shape of the enzyme,

changing the shape of the active site

 The enzyme is now dysfunctional because the

substrate now cannot bind to the active site.

 Adding more substrate will not affect the reaction

because the active site is unavailable.
 substrate

The shape of the active

site has changed

Therefore, the
substrate no longer fits
in

enzyme
 Some enzymes have receptor sites away from the
active site called ALLOSTERIC SITES

 (These enzymes are usually proteins made of

several subunits each with an active site)

 Substance that bind to the allosteric sites may

inhibit or stimulate (increase) the enzyme activity.
 Binding an ACTIVATOR to an allosteric site
stabilizes the protein conformation

 This keeps all the active sites available for the

substrates to bind to them.
*Binding of an allosteric inhibitor (a type of
noncompetitive inhibitor) stabilizes the
inactive form of the enzyme
 The binding of an activator or an inhibitor
affects the activity of all the active sites on
the enzyme
 Method of controlling metabolic pathways

 Negative feedback inhibition is like a

thermostat.

 When it is cold, the thermostat turns on the

heater to produce heat.

 When it is too warm, the heat will cause the

thermostat to turn off the heater
Cold Thermostat Heater Heat

INHIBITS

 Heat has a negative effect on the thermostat;

 A build up of product inhibits the enzymes and the

reaction
 Many enzymatic pathways are regulated by
feedback inhibition

 As the enzyme’s end product accumulates, it

inhibits the enzyme by binding to the first
enzyme in the pathway.

 This shuts down the entire sequence.

 *

© 2017 Paul Billiet ODWS

 As the product is used up over time, the concentration
of product decreases

 The inhibition product will detach from the enzyme

allowing it to become active once again and produce
product.

 When the product concentration gets too high again, the

product will once again allosterically inhibit the enzyme
* 1. inhibit uncompete
* 2. contoh tisp inhibit dibidang kesehatan,
pertanianm, pangan, aplikasui
* Kapan inhibit lepas
* Uncompetitive inhibition is another class of reversible
inhibition.
* The inhibitor binds ONLY to the enzyme-substrate complex in
this process.
* Binding of the inhibitor prevents the formation of products by
causing a change in the interaction between the enzyme and
the substrate.

*
* Zidovudine is a potent HIV inhibitor that decreases levels
of HIV in the blood by inhibiting the replication of HIV. The
enzyme that inhibited by Zidovudine is glukoronil
transferase

*
* Penisilin dan Aspirin
Senyawa obat ini terikat pada tapak aktif, dan enzim kemudian
mengubah inhibitor menjadi bentuk aktif yang bereaksi secara
ireversibel dengan satu atau lebih residu asam amino.

*
* Merupakan Inhibitor Protein Dipeptidyl Peptidase-4, Generasi
Baru Obat Antidiabetes
* Obat ini menghambat degradasi hormon inkretin yang
berfungsi mengatur dan mengontrol glukosa darah.3 Interaksi
antara senyawa analog sitagliptin dengan DPP4 sudah berhasil
dikristalkan dan dipublikasikan serta dimanfaatkan untuk
merancang obat baru oleh Biffu dan kawan-kawan.

*
*Obat antiinflamasi golongan non steroid bekerja melalui
mekanisme lain seperti isoenzim COX-1 dan COX-2. Enzim
COX ini berperan dalam memacu pembentukan prostaglandin
dan tromboksan dari asam arakhidonat. Prostaglandin
merupakan molekul pembawa pesan pada proses inflamasi.
Inhibisi sintesis prostaglandin dalam mukosa lambung sering
kali dapat menyebabkan kerusakan gastrointestinal (dispepsia,
mual, dan gastritis). Efek samping yang paling serius adalah
pendarahan gastrointestinal (Neal, 2006). Pemberian obat pada
dosis yang rendah secara terus-menerus digunakan sebagai
terapi pada penderita stroke untuk mencegah terjadinya stroke
berikutnya. Selain itu, penghambatan COX juga berakibat pada
peningkatan produksi leukotrien yang berperan dalam proses
kontraksi pada bronkus sehingga dapat memicu terjadinya asma
(Roberts & Morrow, 2011).
* Indometasin merupakan suatu senyawa turunan indol termetilasi
seperti yang terlihat pada Gambar 6. Efek antiinflamasi dicapai melalui
mekanisme penghambatan enzim siklooksigenase secara tidak selektif,
obat ini juga diketahui dapat menghambat migrasi leukosit
polimorfonuklear (Caramis & Varonos, 1980; Roberts & Morrow, 2001).
Indometasin banyak digunakan untuk mengatasi nyeri pada penyakit-
penyakit seperti osteoarthritis, rheumatoid arthritis, ankylosing
spondyliti, bursitis, dan tendinitis.
* Statin drugs such as lipitor compete with HMG-CoA(substrate)
and inhibit the active site of HMG CoA-REDUCTASE (that bring
about the catalysis of cholesterol synthesis).
* malonatdan oksalosuksinat, yang bersaing dengan substrat
untuk berikatan dengan enzim suksinat dehidrogenase, yaitu
enzim yang bekerja pada substrat oseli suksinat.