Dispel some mist on circulating biopterins: measurement, physiological interval and pathophysiological implication

Abstract

Abstract BACKGROUND: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and biopterin (B), are critical cofactors for aromatic amino acid and nitric oxide synthases. Apart from their acknowledged significance in various endocrine diseases, there are noticeable research gaps and controversies on related experimental outcomes, for example analytical art, physiological interval and pathophysiological implication. METHODS: Combining chemical derivatization and cold-induced phase separation in sample pretreatment, a new LC-MS/MS method was developed for global profiling biopterins in plasma. On this basis, the impact of anti-oxidation was specifically clarified. Afterwards, 215 apparently normal participates were enrolled to investigate the physiological interval of biopterins. And the relations between biopterins and the routine biochemical indicators were analyzed to explore the biopterins’ pathophysiological implications. RESULTS: The method was validated to be reliable for detecting biopterins in the whole physiological ranges. Timely anti-oxidation was proved essential for accurate assessment of biopterins. The observed overall mean (± SDs) levels were 3.51 (± 0.94) ng/mL for BH4, 1.54 (± 0.48) ng/mL for BH2, 2.45 (± 0.84) for BH4/BH2 and 5.05 (± 1.14) ng/mL for total biopterins. The status of all the biopterins was tightly correlated with age. The levels of BH2 and BH4/BH2 revealed gender-specific differences. In specific, the healthy problems of hyperuricemia and overweight could cause distinct change on biopterins status in vivo. CONCLUSIONS: Coupling with proper anti-oxidation, the newly developed method can accurately determine the global biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental but inspiring supports for further biopterins-based researches.