FLAVONOIDS : METABOLIC CHANGES AND EFFECT ON ENZYME SYSTEMS

Cilj: Cilj ovog diplomskog rada je opisati metabolizam različitih skupina flavonoida u ljudskom organizmu te njihov utjecaj na enzimske sustave, a ovisno o strukturnim značajkama koje flavonoidi moraju posjedovati da bi se taj učinak ostvario. Materijali i metode: Osnovna struktura flavonoida sastoji se od dva benzenska prstena povezana propanskim lancem. Obično se, prema strukturnim značajkama, flavonoidi dijele u šest glavnih skupina, a to su: antocijanidini, flavan-3-oli, flavoni, flavanoni, izoflavoni i flavonoli. Ulaskom u ljudski organizam, flavonoidi su podložni različitim metaboličkim promjenama od kojih se mogu izdvojiti reakcije hidrolize i hidroksilacije (monooksigenacije) kao reakcije prve faze metabolizma, a od reakcija druge faze značajne su: glukuronidacija, sulfokonjugacija i metilacija. Rezultati: Metabolizam flavonoida započinje reakcijom hidrolize kojom se iz glikozida flavonoida oslobađa aglikonski dio molekule čime se omogućava apsorpcija. Zatim slijede reakcije prve faze metabolizma koje se poglavito odvijaju u jetri pod utjecajem enzima superporodice citokrom P450, a nakon njih i reakcije druge faze od kojih se ističu reakcije glukuronidacije i sulfatacije. Flavonoidi uglavnom djeluju inhibicijski na različite enzimske sustave, a u ovom radu obrađeni su inhibicijski učinci na: ciklooksigenaze (COX), lipooksigenaze (LOX), enzime citokrom P450 (CYP), ksantin oksidoreduktaze (XOR), fosfodiesteraze (PDE), fosfolipazu A2 (PLA2) i dr. Istraživanja su pokazala da inhibicijski učinci ovise o strukturnim značajkama flavonoida. Zaključak: Metaboličke promjene flavonoida bitno mijenjaju njihova svojstva i biološke učinke u ljudskom organizmu. Djelovanjem na enzimske sustave flavonoidi ostvaruju različite farmakološke i biokemijske učinke te stoga posjeduju veliki potencijal u prevenciji i terapiji različitih vrsta oboljenja.Objectives: The aim of this diploma thesis is to describe the metabolism of different flavonoid groups in human body and to describe the effect of flavonoids on the enzymatic systems and structural characteristics that flavonoids must have in order to achieve this effect. Material and Methods: The basic structure of flavonoids consists of two benzene rings connected by propan chain. Usually, according to structural characteristics, flavonoids are divided into six major groups: anthocyanidines, flavan-3-ols, flavones, flavanones, isoflavones and flavonols. By entering into a human organism, flavonoids are subject to various metabolic changes. Hydrolysis and hydroxylation (monooxygenation) reactions (first phase metabolic reactions) and glucuronidation and sulfation (second phase metabolic reactions) can be extracted. Results: Metabolism of flavonoids begin with hydrolysis during which flavonoids are set free from aglycone part of the molecule to allow absorption. After absorption, flavonoids are transported to liver where they undergo extensive metabolism which includes first phase of metabolic reactions and also conjugation reactions (glucuronidation and sulfation). Usually, flavonoids inhibit various enzyme systems. Some of the enzymes that have been inhibited by flavonoids are: cyclooxygenase (COX), lipooxygenase (LOX), cytochrome P450 enzymes (CYP), xanthine oxidoreductase (XOR), phosphodiesterase (PDE), phospholipase A2 (PLA2). Structural characteristics of flavonoids play hugh role in their effect on enzymes. Conclusion: Metabolic changes of flavonoids significantly alter properties and biological effects in the human body. By acting on enzyme systems, flavonoids accomplish different pharmacological and biochemical effects and thus have great potential in preventing and treating various types of diseases