Studies in the handling and absorption of biopterin derivatives in man

Abstract

The Crithidia fasciculata assay of pterins in biological fluids has been developed and the parameters which affect it assessed, The effects of various pteridines on the assay demonstrated sufficient specificity to allow qualitative deductions from results. Reproducibility and recovery experiments confirmed that it was usable for quantitative analysis, The narrow range of Crithidia active pterins in man with values for serum ranging from 0.4 ne/om> to 3.6 ng/om? and for urine 0.34 ug/em? to 6.9 ue/om? suggest homeostatic maintainance of normal serum concentrations, Urinary excretion was around 1.6 mg/day and all evidence supported an endogenous source. Tetrahydrobiopterin was poorly absorbed in man and biopterin, was better absorbed. Concentrations of Crithidia factor in different areas of brain from different cadavers ranged from 20 ng/g to 500 ng/g wet weight and in liver from 41 ng/g to 163 ng/g. Brain levels probably reflect the role of tetrahydrobiopterin in the hydroxylation of tyrosine to dopa and tryptophan to 5—hydroxytryptophan. Serum Crithidia factor levels in phenylketonuria were elevated as a result of hyperphenylalaninaemia, This raised level could arise either from increased synthesis or altered tissue/body fluid partition. In kidney disease, where urinary concentration is impaired, urinary levels were extremely low and serum levels significantly elevated. Low serum values were found in leukaemia, pernicious anaemia, psoriasis, myeloma, regional enteritis and rheumatoid arthritis, all diseases in which there is alteration in the pattern of cell division. The other disease investigated in which there were low serum levels was schizophrenia. Serum values not significantly at variance with controls were found in cirrhosis, epileptics on anticonvulsants, treated Parkinsons disease and carcinoma. The last group was small in number. Significantly low urine levels were found in rheumatoid arthritis and controlled epilepsy but not in schizophrenia. Urinary concentrations of Crithidia factor are dependant on urinary flow which could mask small changes in output of biopterin derivatives unless timed and measured collections are made. Raised serum levels of biopterin derivatives in man following oral and intravenous methotrexate suggest that the pteridine ring could be derived from folate if normal metabolism is blocked. Confirmation of this was given by the increase in serum Crithidia factor following folic acid and 5—formyltetrahydrofolic acid in patients on methotrexate, which contrasted to the total absence of response to folates in unmedicated subjects. .