In the last fifteen years, genomics and other -omics sciences have revolutionized our understanding of biological processes at the molecular level. An illustrative example is urate metabolism. Before the publication of the complete human genome, in 2003 it was believed that a single enzyme (urate oxidase) was responsible for uricolysis that is the conversion of urate into the more soluble allantoin. Now we know with great detail that this process requires the consecutive action of three enzymes that have been lost by gene inactivation in our hominoid ancestor. Similarly, a single urate transporter (URAT1) was known at that time. Now we have evidence that urate homeostasis depends on a complex set of transporters located on the epithelial cells of the kidney and the intestine. In this review article, we give an account of the recent discoveries on urate metabolism and how these discoveries can be applied to the development of novel drugs to treat hyperuricemia, tumor lysis syndrome and the Lesch-Nyhan disease.
Negli ultimi quindici anni la genomica e le altre scienze "omiche" hanno rivoluzionato la nostra conoscenza dei processi biologici a livello molecolare. Un esempio è il metabolismo dell’urato. Prima della pubblicazione del genoma umano, nel 2003, un solo enzima (urato ossidasi) era ritenuto responsabile della degradazione dell’urato (uricolisi), ovvero della sua conversione ad allantoina, un composto molto più solubile e facilmente eliminabile. Oggi sappiamo che questo processo richiede l’azione sequenziale di tre enzimi, che sono stati persi per inattivazione genica in un antenato degli ominoidi. Allo stesso modo, un solo trasportatore dell’urato (URAT1)era noto all’epoca. Attualmente abbiamo evidenze che nelle cellule epiteliali di reni e intestino vi sia un’intera batteria di trasportatori, non ancora del tutto caratterizzati, deputati alla regolazione dell’omeostasi dell’urato. In questa rassegna, riportiamo alcune recenti scoperte sul metabolismo dell’urato, evidenziandone la possibile applicazione allo sviluppo di nuovi farmaci per il trattamento dell’iperuricemia, della sindrome da lisi tumorale e della malattia di Lesch-Nyhan.
[Recent advances in urate metabolism] / Mori, Giulia; Percudani, Riccardo. - In: GIORNALE ITALIANO DI NEFROLOGIA. - ISSN 1724-5990. - 33:(2016), pp. 54-63.
[Recent advances in urate metabolism]
Mori, Giulia;PERCUDANI, Riccardo
2016-01-01
Abstract
In the last fifteen years, genomics and other -omics sciences have revolutionized our understanding of biological processes at the molecular level. An illustrative example is urate metabolism. Before the publication of the complete human genome, in 2003 it was believed that a single enzyme (urate oxidase) was responsible for uricolysis that is the conversion of urate into the more soluble allantoin. Now we know with great detail that this process requires the consecutive action of three enzymes that have been lost by gene inactivation in our hominoid ancestor. Similarly, a single urate transporter (URAT1) was known at that time. Now we have evidence that urate homeostasis depends on a complex set of transporters located on the epithelial cells of the kidney and the intestine. In this review article, we give an account of the recent discoveries on urate metabolism and how these discoveries can be applied to the development of novel drugs to treat hyperuricemia, tumor lysis syndrome and the Lesch-Nyhan disease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.