Vol. 9, No 3, 2002 pp. 201 - 206
UC 615.363
COMPETITIVE INHIBITORS OF ENZYMES
AND THEIR THERAPEUTIC APPLICATION
Gordana Bjelaković, Ivana Stojanović, Goran B. Bjelaković1,
Dušica Pavlović, Gordana Kocić, Angelina Daković-Milić
Institute of Biochemistry, 1Clinic
of Hepato-Gastroenterology, Faculty of Medicine, University of Niš, Serbia
Summary. Enzymes catalyze virtually every biochemical process in
the cell. The usefulness of the most important pharmaceutical agents, antimetabolites,
is based on the concept of competitive enzyme inhibition. The antimetabolites
are structural analogues of normal biochemical compounds. As competitive
inhibitors they compete with the naturally substrate for the active site
of enzyme and block the formation of undesirable metabolic products in
the body. Antibacterial, antiviral and anticancer pharmaceutical agents
are among numerous examples of antimetabolites. Sulfa drags, sulfanilamide,
structural analogs of amino acids (cycloserine, L-fluoroalanine), folic
acid antagonists (4-amino-10-methyl folic acid=methotrexate), analogues
of purine and pyrimidine (6-mercaptopurine, allopurinol, 5-fluorouracil,
5-azacytidine), inhibitors of polyamine biosynthesis (difluoromethyl ornithine,
methylglyoxal-bis (guanyl hydrazone)) are the most used in modern chemotherapy
The use of enzyme inhibitors, antimetabolites, beside the therapeutic significance
has also provided valuable informations about enzyme mechanisms and has
helped to define some metabolic pathways.
Key words: Enzyme inhibitors, sulfa drugs, antimetabolites,
folic acid antagonists, purine and pyrimidine analogues, polyamines antagonists,
chemotherapy
KOMPETITIVNI INHIBITORI ENZIMA I NJIHOVA
TERAPIJSKA PRIMENA
Kratak sadržaj: Enzimi katalizuju gotovo sve biohemijske procese
u ćeliji. Primena mnogih lekova u medicini, antimetabolita, bazirana je
na konceptu kompetitivne enzimske inhibicije. Antimetaboliti se veoma malo
strukturalno razlikuju od prirodnih enzimskih supstrata. Svoja specifična
dejstva ispoljavaju ponašajući se kao kompetitivni inhibitori određenih
enzimskih reakcija blokirajući formiranje neželjenih metabolita u organizmu.U
antimetabolite spadaju antibakteriski, antivirusni i antitumorski lekovi.
Najzastupljeniji od njih jesu sulfonamidi, strukturni analozi amino kiselina
(cikloserin, 5-fluoroalanin), antagonisti folne kiseline (4-amino-10-metil
folna kiselina -metotreksat), analozi purina i pirimidina (6-merkaptopurin,
alopurinol, 5-fluorouracil, 5-azacitidin), inhibitori biosinteze poliamina
(a-difluorometil ornitin, metillglioksal-bis (guanil hidrazone=MGBG).
Primena enzimskih inhibitora, antimetabolita,osim terapiskog značaja,
omogućava bolje razumevanje raznih metaboličkih puteva, kao i bolje upoznavanje
mehanizma delovanja enzima.
Ključne reči: Enzimska inhibicija, sulfonamidi, antimetaboliti,
antifolati, analozi purina i pirimidina, analozi poliamina, hemioterapija
