Detalji o radu
Broj pregleda rada: 442
Naslov: Metabolizam kofeina posredovan citokromom P450 1A2
Godina: 2024
Autori: MATEA GADŽA, MARTIN KONDŽA
Sažetak: UVOD: Kofein je najkorišteniji psihostimulans na svijetu, a ljudi ga konzumiraju putem različitih
pića, hrane, ali i lijekova. Kofein se gotovo u potpunosti metabolizira, a oko 3% kofeina se izlučuje
nepromijenjeno urinom. Glavni put metabolizma kod ljudi (70-80%) je N-3 demetilacija u
paraksantin putem citokrom P450 1A2 enzima (CYP1A2) te se zbog toga kofein koristi kao marker
supstrat za dokazivanje aktivnosti CYP1A2. Još neki od supstrata ovog enzima su klozapin, teofilin,
takrin i meksiletin. Aktivnost CYP1A2 pokazuje izraženu intra- i interindividualnu varijabilnost.
Pušenje i neke namirnice kao što je meso s roštilja djeluju kao induktori CYP1A2. Trudnoća i
patološka stanja poput hepatitisa B produžuju poluvrijeme eliminacije kofeina kao supstrata.
Oralni kontraceptivi i kinoloni enoksacin i ciprofloksacin inhibiraju CYP1A2. Također su poznati
genski polimorfizmi enzima CYP1A2 koji dovode do usporenog (CYP1A2*1F) ili ubrzanog
(CYP1A2*1A) metabolizma. Budući da je uporaba kofeina toliko raširena, poznavanje njegove
farmakokinetike i farmakogenomike vrlo je važno za javno zdravlje. CILJ: Cilj istraživanja je bio
dokazati da je paraksantin glavni metabolit biotransformacije kofeina posredstvom CYP1A2.
MATERIJALI I METODE: Odrađen je postupak metaboličke biotransformacije kofeina posredovan
CYP1A2 enzimima istodobnom inkubacijom enzima, supstrata i generirajućeg sustava pri pH=7,4
i temperaturi od 37°C. Identifikacija uzoraka radila se pomoću tankoslojne kromatografije i
tekućinske kromatografije visoke djelotvornosti. Ispitivanja su rađena u triplikatu. REZULTATI:
CYP1A2 je uključen u metabolizam kofeina. Glavni metabolit je paraksantin. ZAKLJUČAK: Kofein
se metabolizira putem CYP1A2 kao i 9% poznatih lijekova i 15% ksenobiotika te je potreban oprez
prilikom zajedničke konzumacije zbog mogućih postupaka inhibicije ili indukcije.
Znanstvena područja:
FARMACIJA
Naslov (eng): Caffeine metabolism mediated by cytochrome P450 1A2
Sažetak (eng): INTRODUCTION: Caffeine stands as the most widely consumed psychostimulant globally.
People ingest caffeine through various beverages, food items and medications. Nearly all caffeine
undergoes metabolism, with approximately 3% excreted unchanged in urine. In humans, the
primary metabolic pathway (70-80%) involves N-3 demethylation to paraxanthine via cytochrome
P450 1A2 enzyme (CYP1A2), making caffeine a useful marker for assessing CYP1A2 activity.
Several substrates of this enzyme include clozapine, theophylline, tacrine and mexiletine.
CYP1A2 activity exhibits significant intra- and interindividual variability. Smoking and certain
foods like grilled meat act as inducers of enzyme. Pregnancy and pathological conditions such as
hepatitis B prolong the elimination half-life of caffeine as a substrate. Oral contraceptives and
quinolones enoxacin and ciprofloxacin inhibit CYP1A2. Additionally, gene polymorphisms of
CYP1A2 enzyme are also known, which lead to slowed (CYP1A2*1F) or accelerated (CYP1A2*1A)
metabolism. Given the widespread use of caffeine, understanding its pharmacokinetics and
pharmacogenomics holds paramount importance for public health. AIM: The aim of the research
was to demonstrate that paraxanthine is the main metabolite of caffeine biotransformation
mediated by CYP1A2. MATERIALS AND METHODS: The procedure of caffeine metabolic
biotransformation mediated by CYP1A2 enzymes was performed by simultaneous incubation of
enzyme, substrate and generating system at pH=7,4 and temperature of 37°C. Sample
identification was preformed using thin-layer chromatography and high-performance liquid
chromatography. The experiments were conducted in triplicate. RESULTS: CYP1A2 is involved in
the metabolism of caffeine, with paraxanthine being the main metabolite. CONCLUSION:
Caffeine's metabolism predominantly occurs via CYP1A2, like 9% of known drugs and 15% of
xenobiotics. Caution is advised when consuming these substances.