Sema UYSAL, Sümeyya AKYOL, Rukiye HASGÜL, Ferah ARMUTÇU, M. Ramazan YİĞİTOĞLU

Çok yönlü bir enzim: Paraoksonaz

Paraoksonaz enzimi ilk olarak organofosfor zehirlenmesine karşı koruyucu bir bariyer olarak tanımlanmıştır. Bu enzim hakkında son yıllarda oldukça fazla sayıda araştırma yapılmış olup, sahip olduğu fonksiyonlar ve hastalıklardaki rolü hakkında büyük ilerleme kaydedilmiştir. Bu derleme makalesinde, paraoksonaz enziminin normal fizyolojik fonksiyonlarının yanıbaşında hastalıklar ın etyopatogenezinde sahip olduğu rolü de gözden geçirmeyi amaçladık. Paraoksonaz 1 (PON1) enzimi, esteraz ve laktonaz aktivitesi gösteren yüksek dansiteli lipoprotein (HDL) ilişkili bir enzimdir. Herhangi bir kritere göre belirlenmiş bir insan populasyonunda serum PON1 aktivitesi en az 40 kat değişebilir. Bu değişkenliğin çoğu PON1 geninin kodlama (Q192R, L55M) bölgesinde ve promotor (T-108C) bölgedeki genetik polimorfizm ile izah edilebilir. Oksidatif strese karşı önemli bir antioksidan olarak görev yapan bu enzim, kanser ve kardiyovasküler hastalıklar başta olmak üzere birçok hastalığın patogeneziyle ilişkilendirilmektedir. Enzimin transkripsiyon ve translasyon başta olmak üzere düzenleyici mekanizmalar ı ile birlikte moleküler mekanizmasının daha iyi anlaşılması, enzimin antioksidan etkilerini potansiyalize etmek için agonistlerden yararlanmada bize yardımcı olacaktır.

Paraoxonase: A multifaceted enzyme

Paraoxonase enzyme has initially been identified as a protective barrier against organophosphorus poisoning. In the recent years, a wide range of investigations were conducted on this enzyme and the knowledge about its functions and the etiopathogenetic role in some diseases has been clarified in depth. In this review article, we aimed to evaluate the normal physiological functions of PON enzyme as well as the etiopathogenetic role of this enzyme in several diseases. PON1 is a high density lipoprotein-associated enzyme that have esterase and lactonase activities. In a human population selected by any of the criteria, serum PON1 activity can be changed by at least 40-fold. Genetic polymorphisms in the coding region (Q192R, L55M) and in the promoter region (T- 108C) may account for most of these variations. PON, as an important anti-oxidant enzyme against oxidative stress, has been implicated in the pathogenesis of a number of disorders including cancer, cardiovascular and several other diseases. A better understanding of molecular mechanisms of the enzyme along with regulatory circuits including transcription and translational mechanisms will help us to utilize agonists to potentiate the antioxidant actions of the enzyme.

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