Considerable evidence has shown that elevated plasma or cerebrospinal fluid (CSF) urate levels correlated with a reduced risk of Parkinson's disease (PD). Based on its anti-oxidative properties, urate might serve as one of promising neuroprotective candidates for PD. However, how urate is transported through cell membranes to exert its effects inside the cells in PD is largely unknown. To eluci...

Urate oxidase, or uricase (EC 1.7.3.3), is a peroxisomal enzyme that catalyzes the oxidation of uric acid to allantoin in most mammals. In humans and certain other primates, however, the enzyme has been lost by some unknown mechanism. To identify the molecular basis for this loss, urate oxidase cDNA clones were isolated from pig, mouse, and baboon, and their DNA sequences were determined. The m...

1. When changes in urine flow rate were induced by vasopressin administration in eight subjects, urate excretion decreased by a mean of 14% and was positively correlated with urine flow rate (r = 0.88, P less than 0.01). The effect of vasopressin on urate excretion was not influenced by prior changes in extracellular fluid volume. 2. Mannitol administration in a dose sufficient to prevent vasop...

Urate is a major antioxidant as well as the enzymatic end product of purine metabolism in humans. Higher levels correlate with a reduced risk of developing Parkinson's disease (PD) and with a slower rate of PD progression. In this study we investigated the effects of modulating intracellular urate concentration on 1-methyl-4-phenyl-pyridinium (MPP(+))-induced degeneration of dopaminergic neuron...

Although a genetic predisposition to gout has been recognised for centuries, its mechanism has never been defined. This study was designed to determine whether this factor might be the renal clearance of urate, which is an important determinant of the concentration of urate in serum. In this study the renal clearance of urate was examined in 37 pairs of normouricaemic twins to determine whether...

1. The renal mechanism for urate excretion in the Dalmatian dog resembles that in birds. Urate is cleared at a rate considerably greater than the glomerular filtration rate, indicating that its excretion is the result of both glomerular filtration and active tubular secretion. The basic physiological mechanisms involved in the anomalous purine metabolism of the Dalmatian are indicated and their...

(1) Calcium greatly increased crystallization of monosodium urate in otherwise pure water, by enhancing both nucleation and growth. (2) Acid accelerated urate nucleation, both by its direct action and indirectly by increasing the free calcium in physiological fluids. (3) Synovial fluid from one gouty patient accelerated urate nucleation, while that from one rheumatoid patient inhibited nucleati...

G out is a monosodium urate crystal deposition disease. Formation of the crystals requires high serum uric acid levels; the local factors responsible for their predilection for the joints are only started to be grasped. 2 Steady serum urate levels result from the balance between its production and excretion; hyperuricaemia results when formation is increased or difficulties in (mostly) renal ex...

The theory of the "four-component model" of urate excretion in humans is reevaluated, considering that a decrease in urate excretion induced by drugs like pyrazinamide or by endogenous compounds like lactate and ketone bodies might be a result of stimulation of urate reabsorption and not, as previously considered, of inhibition of urate secretion.

Inhibition of [14C]-urate uptake by uricosuric and antiuricosuric agents was investigated in human brush-border membrane vesicles, urate being transported either by anion exchange mechanisms or by voltage sensitive pathway. The IC50 for drugs on [14C]-urate uptake in vesicles loaded with 1 mM cold urate or with 5 mM lactate was, respectively: 0.7 and 0.3 microM for benzbromarone; 6 and 4 microM...