Cyclic-FMN Is a Detectable, Putative Intermediate of FAD Metabolism
Free flavin adenine dinucleotide (FAD) is metabolized to flavin mononucleotide (FMN) and adenine monophosphate (AMP) by hydrolases and to 4',5'-cyclic phosphoriboflavin (cFMN) and AMP by the triose kinase FMN cyclase (TKFC). Yet, the lack of analytical standards for cFMN might have resulted in the incidence of cFMN in biological specimens being underreported. To address this shortcoming, cFMN was synthesized from either FMN or FAD. The optimization of the FAD to cFMN reaction conditions revealed that an equimolar ratio of ZnSO<sub>4</sub> and FAD yielded pure cFMN upon the precipitation of AMP-Zn salts. cFMN is stable to aqueous acidic and basic conditions and is readily extracted from biological samples for detection by liquid chromatography coupled with mass spectrometry. Although cFMN is hydrolyzed by liver tissue extracts to FMN and riboflavin, the mechanisms for this conversion remain elusive.
Authors
- Luxene Belfleur
- Mathias Ziegler (ORCID: https://orcid.org/0000-0001-6961-2396)
- Juha P. Kallio (ORCID: https://orcid.org/0000-0003-3092-4012)
- Wito Richter (ORCID: https://orcid.org/0000-0001-5588-9060)
- Marie E. Migaud (ORCID: https://orcid.org/0000-0002-9626-2405)
- Natalie R. Gassman
Institutions
- University of Alabama at Birmingham (US)
- USA Mitchell Cancer Institute (US)
- University of Bergen (NO)
- University of South Alabama (US)
Publication Details
- Journal
- Biomolecules
- Published
- 2026-01-21
- DOI
- https://doi.org/10.3390/biom16010175
- Primary Topic
- Folate and B Vitamins Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00