The Transport and Excretion of Uric Acid in Man. I. True Uric Acid in Normal Cerebrospinal Fluid, in Plasma, and in Ultrafiltrates of Plasma

Abstract

Human cerebrospinal fluid has been reported to contain a relatively small concentration of uric acid compared to that of plasma (cf. Table II). However, it is not known what proportion of these reported uric acid values is due to chromogenic substances similar to those giving the color reaction for uric acid in plasma (1). The introduction of enzymatic methods for determining uric acid specifically (2 to 5) has made reexamination of spinal fluid values advisable, particularly with regard to their relation to plasma ultrafiltrates. SUBJECTSCerebrospinal fluids 2 were obtained by lumbar puncture from individuals suspected of neurosyphilis and from others undergoing routine follow-up after antiluetic therapy. Those fluids which were serologically and Pandy negative were combined into 10-ml. pools, each pool representing 5 individuals. Total and urea-cyanide reagents. The concentration of uric acid equivalent to the color developed is termed total rate.2. Another (2-ml.) aliquot of the specimen is treated with uricase at pH 9.1 to destroy the uric acid present. It is then treated as above, the color developed being termed chromogen.3. The difference between the values for total urate and for chromogen represents the amount of uric acid destroyed by the specific enzyme and is therefore termed true rate.The actual size of the aliquots given in the preceding paragraph is that used in plasma determinations; cerebrospinal fluid contains so little urate that it is advisable to use twice or 3 times these amounts.The nature of the chromogenic substances in plasma and urine which give the color reaction for urate has been discussed recently (1) and will be reviewed more comprehensively in a forthcoming publication (6). A portion of the chromogen is non-purine in origin, but another portion is due to an incompletely characterized purine metabolite (or metabolites) of endogenous origin. In addition, methylurates from the methylxanthines of dietary origin contribute to the chromogen.The normal plasma urate values quoted are based upon repeated determinations on 31 normal individuals and are similar to the values obtained by Bulger and Johns (3) with a uricase method.Plasma for ultrafiltration was obtained from blood drawn in a heparinized syringe and immediately centrifuged; no attempt was made to preserve the normal carbon dioxide content. Ultrafiltrates of plasma were obtained by a modification of the method of Lavietes (7). The membranes used were DuPont No. 600 cellophane, soaked 3 days at 0°before used.8 RESULTSThe results of the urate partition in pooled normal cerebrospinal fluid are given in Table I, together with the average normal concentrations in plasma and the calculated C.S.F./plasma ratios. These data show that normal human cerebrospinal fluid appears to contain, on the average, only 6The cellophane membranes used in ultrafiltration were made available through the cooperation of E. I. du Pont de Nemours Co. 991

The Transport and Excretion of Uric Acid in Man. Ii. The Endogenous Uric Acid-Like Chromogen of Biological Fluids

“…Observations on ultrafiltrates of human plasma ( [10], Table III) show considerably less plasma binding of chromogen than of true urate, when cellophane ultrafiltration is used as the criterion of binding. Moreover, the C.S.F./plasma ratio for chromogen is considerably greater than for true urate ( [ 10], Table I).…”

“…Unlike true rate, chromogen is not attacked by uricase. It appears to be somewhat more freely ultrafiltrable from plasma through cellophane than is true urate ( [10], Table III). It is not deposited in the gouty tophus (Table VI).…”

The Renal Mechanism for Urate Excretion in Man 1

“…Some observers have reported non-filterability of the plasma urate, presumably due to proteinbinding or polymerization, but the magnitude of the bound fraction, 4-24%o (1), and 23% (2) has not been nearly sufficient to account for the difference between the clearances of urate and inulin. In a number of other studies (3)(4)(5) of the behavior of the uric acid of normal serum on ultrafiltration or dialysis, relatively little or no binding has been detected.…”

Inhibition of Iron-Catalyzed Oxidations by Attainable Uric Acid and Ascorbic Acid Levels: Therapeutic Implications for Alzheimer’s Disease and Late Cognitive Impairment

“…At 0.1 mmol/kg of body weight, hypoxanthine orally raised serum uric acid levels by 2.4 8 0.2 mg/dl (mean 8 SE) in normal adults [32] . In subjects with higher plasma uric acid levels in gout, CSF levels averaged as high as 1.79 mg/dl at average plasma level of 7.36 mg/dl [34] .…”

“…CSF levels of urate in man are generally only about 6-15% of the concomitant usual plasma or serum urate levels of about 3-5 mg/dl [34] . Levels are attainable higher as measured in patients with gout [34] .…”