uric acid transport and disease英文教材.PDFVIP

Science in medicine Uric acid transport and disease 1 2 Alexander So and Bernard Thorens 1Service de Rhumatologie, Department of Musculoskeletal Medicine, and 2Department of Physiology and Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant prop- erties that may be protective but can also be pro-oxidant, depending on its chemical microenvi- ronment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hyperten- sion, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metab- olism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development. Introduction dietary changes brought about by increasing prosperity, increased Uric acid, a weak organic acid with a pK a of 5.75, is present prin- life expectancy, the increased use of hypertensive agents, as well as cipally as monosodium urate (MSU) at physiological pH values. aging of the overall population. Whereas in humans an