Cerebrospinal fluid, purines

Mutations in the gene for adenylosuccinate lyase (ASL), inherited as an autosomal recessive disorder in purine metabolism, are associated with severe mental retardation and autistic behavior, but apparently not self-mutilation [10, 11]. This enzyme catalyzes two distinct reactions in the de novo biosynthesis of purines the cleavages of adenylosuccinate (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAR), both of which accumulate in plasma, urine and cerebrospinal fluid of affected individuals [12]. Measurements of these metabolites in urine... 

Dobolyi A, Reichart A, Szikra T, SzLlagy N, Kekesi AK, et al. 1998. Analysis of purine and pyrimidine bases, nucleosides and deoxynucleosides in brain microsamples (microdialy-sates and micropunches) and cerebrospinal fluid. Neuro-chem Int 32 247. 

Kuracka, L. Kalnovicova, T. Liska, B. Turcani, P. HPLC method for measurement of purine nucleotide degradation products in cerebrospinal fluid. Clin. Chem. 1996, 42 (5), 756-760. 

We have used an adaptation of the fluorimetric assay described by Gardiner to measure purine levels in ultrafiltrates of human plasma (collection from different sites), cerebrospinal fluid and bone marrow aspirates. The assay technique allows the sequential determination of three major purine components, i.e. Hypoxanthine (Hx) plus Xanthine (X), Inosine (IR) and Adenosine (AR). 

Total purine levels in cerebrospinal fluid were always elevated when compared with simultaneous peripheral venous plasma (P < 0.05). AR was much lower, being detected in only 3 of 8 CSF specimens. ... 

Purine and pyrimidine bases are present in plasma and urine because of their low renal threshold, urine is preferred for analysis. Little use has been found for the analysis of cerebrospinal fluid. As a 24-h-urine sample is often difficult to obtain, the excretion of purine and pyrimidine bases (and nucleosides) is best expressed as mol/mol creatinine. Urine uric acid declines with age from values of 0.5-1.5 mol/mol creatinine in the first year of life to 0.2-0.5 mol/mol creatinine in adulthood [6]. Reference values for the most common purines/pyrimidines are given in Table D.l. 

In support of its role as an intermediate in purine metabolism, adenylosuccinic acid has been isolated from mammalian liver (164) and from Penidllium chrysogenum (166). The free base, adeninosuccinic acid [6-(succinoamino) purine], was identified in human urine (166) and isolated from Neurospora mutants (167, 168). Also, the ribonucleoside derivative of adeninosuccinic acid (adeno lsuccinic acid) has been found in human cerebrospinal fluid (169) and in a Neurospora mutant (168). Another adenylosuccinate compound contained sulfate in a ribos fi -phosphosulfate linkage as well as a peptide residue, but its significance is not known (160). 

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