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Riboflavin transport and metabolism in humans

  • SSIEM 2015
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Recent studies elucidated how riboflavin transporters and FAD forming enzymes work in humans and create a coordinated flavin network ensuring the maintenance of cellular flavoproteome. Alteration of this network may be causative of severe metabolic disorders such as multiple acyl-CoA dehydrogenase deficiency (MADD) or Brown-Vialetto-van Laere syndrome. A crucial step in the maintenance of FAD homeostasis is riboflavin uptake by plasma and mitochondrial membranes. Therefore, studies on recently identified human plasma membrane riboflavin transporters are presented, together with those in which still unidentified mitochondrial riboflavin transporter(s) have been described. A main goal of future research is to fill the gaps still existing as for some transcriptional, functional and structural details of human FAD synthases (FADS) encoded by FLAD1 gene, a novel “redox sensing” enzyme. In the frame of the hypothesis that FADS, acting as a “FAD chaperone”, could play a crucial role in the biogenesis of mitochondrial flavo-proteome, several basic functional aspects of flavin cofactor delivery to cognate apo-flavoenzyme are also briefly dealt with. The establishment of model organisms performing altered FAD homeostasis will improve the molecular description of human pathologies. The molecular and functional studies of transporters and enzymes herereported, provide guidelines for improving therapies which may have beneficial effects on the altered metabolism.

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Acknowledgments

The authors thank: the student M.T. Damiano, (Università degli Studi di Bari “Aldo Moro”) for the aid in figure drawings and Mr V. Giannoccaro (Università degli Studi di Bari “Aldo Moro”) for the technical assistance.

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Authors and Affiliations

  1. Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari “Aldo Moro”, via Orabona 4, I-70126, Bari, Italy

    Maria Barile, Teresa Anna Giancaspero & Piero Leone

  2. Dipartimento DiBEST (Biologia, Ecologia, Scienze della Terra), Unità di Biochimica e Biotecnologie Molecolari, Università della Calabria, via Bucci 4c, I-87036, Arcavacata di Rende, Italy

    Michele Galluccio & Cesare Indiveri

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  1. Maria Barile
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  2. Teresa Anna Giancaspero
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  3. Piero Leone
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  4. Michele Galluccio
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  5. Cesare Indiveri
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Correspondence to Maria Barile.

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Communicated by: Manuel Schiff

This work was supported by PON-ricerca e competitività 2007-2013, MIUR (Ministry of Instruction, University and Research - Italy) project 01_00937: “Modelli sperimentali biotecnologici integrati per la produzione ed il monitoraggio di biomolecole di interesse per la salute dell’uomo” to M.B.

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Supplementary Fig. 1

Sketch representation of FADS gene exons. Assembly of exons for coding actual (FADS-001 and FADS-002) and predicted protein isoforms is highlithed. Length as coded amino acids for each exon is reported (in brackets). Isoform number and accession numbers are reported on the right (DOCX 609 kb)

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Barile, M., Giancaspero, T.A., Leone, P. et al. Riboflavin transport and metabolism in humans. J Inherit Metab Dis 39, 545–557 (2016). https://doi.org/10.1007/s10545-016-9950-0

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  • DOI: https://doi.org/10.1007/s10545-016-9950-0

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