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Pathophysiology and Clinical Manifestations of Gout
Uric acid is the end product of purine catabolism in man. Purines originate from food and the degradation of nucleic acids and nucleotides. Xanthine oxidase (XOD) is the key enzyme in purine degradation. XOD converts hypoxanthine to xanthine and xanthine to uric acid, respectively (Fig. 1). Uric acid is filtered in the glomerulus of the kidney, is almost completely absorbed in the proximal tubules, and secreted more distally (Fig. 2). At physiological pH (<7.4), uric acid exists predominantly in its ionic form (urate). At lower pH, the fraction of uric acid molecules (protonized form) increases. This is important because uric acid possesses a lower solubility than urate. Thus, a decrease in pH, as it occurs in inflammed tissue and in the tubules, facilitates the formation of uric acid crystals, which are the initial cause of gout. Of importance for...