Flavin Coenzymes

Sandro Ghisla, University of Konstanz, Konstanz, Germany
Dale E Edmondson, Emory University, Atlanta, Georgia, USA

Published online: September 2009

DOI: 10.1002/9780470015902.a0000654.pub2

Flavins are yellow chromophores in organisms from bacteria to humans and essential for practically all metabolic processes. They occur in nature in a variety of forms. The core of the flavin cofactor is the (iso)alloxazine nucleus with the most common forms as FMN (flavin mononucleotide) and FAD (flavin-adenine dinucleotide). A number of flavin cofactors are covalently linked to their apoproteins. The covalent linkage is, in general, via a modification of the benzene subnucleus and functional groups of amino acid side chains. As cofactors, flavins are distinguished by their ability to catalyse a variety of different processes involving oxidation-reduction (redox) reactions.

Key Concepts

  • Chemical variation of a basic molecule (the isoalloxazine) leads to several (modified) coenzymes that differ significantly in their catalytic properties.
  • The type and position of the modification is a key determinant for the properties of the (modified) coenzyme.
  • The cofactor interacts with the protein in many different ways. These, in turn, affect the properties of the cofactor as a catalyst. The result is a disparate selection of catalytic functions.

Keywords: FMN; FAD; flavoprotein; alloxazine; cofactor; redox

Figure 1. Structure and nomenclature of flavins and analogues.
Figure 2. Structures of naturally occurring modified flavins. [VIII] carries a covalent linkage from the flavin C8 -methylene position to a protein functional group such as His-N(3), His-N(1), Tyr-O or Cys-S. In [IX] a Cys sulfur is linked to the flavin position C(6). In [IXa] the flavin is linked both to a Cys sulfur to position C(6) and to a His-N(1) of the protein backbone. In [X] the modification is at the benzene C(8) position. [XI] is the chromophore of 8-hydroxy-5-deazaflavins, which additionally carry a modified N(10) side chain R. In [XII] the N(10)-ribityl side chain carries modifications.
Figure 3. Outline of the most used pathway for the chemical synthesis of the flavin nucleus. [XIII] is a xylidine derivative and [XIV] a barbituric acid.
Figure 4. Outline of the biosynthesis of riboflavin [III]. The origin of the components of the xylene ring is denoted in shading in the 8-ribityllumazine [XVI] precursor.
Figure 5. Absorption spectra of the flavin molecule [III] in its different redox states and ionic forms. Note that the semiquinone forms (radical forms) can be stabilized to nearly 100% only when bound to enzymes such as glucose oxidase. The anionic form of free reduced flavin does not show major differences compared to the neutral one in the visible range.
Figure 6. Redox and ionization states of the flavin.
Figure 7. Functions and classes of reactions catalysed by flavoenzymes.
Figure 8. Possible configurations of flavins. The ‘hairpin’ configuration preferred by free FAD in solution is shown on the top. The bottom structure shows the reduced flavin viewed along its N(5)–C(10) axis, along which it can ‘bend’.
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 References
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 Further Reading
    book Chapman SK and Reid GA (eds) (1998) Flavoprotein Protocols, pp. 1–9. [A recent collection of methods applicable to various problems in the context of flavin biochemistry.] Totowa: Humana Press.
    book Chytill F and McCormick DB (eds) (1986) Vitamins and coenzymes part G. Methods in Enzymology, vol. 122. San Diego: Academic Press.
    book Chytill F and McCormick DB (eds) (1986) Vitamins and coenzymes part H. Methods in Enzymology, vol. 123. San Diego: Academic Press.
    other Flavins and Flavoproteins (1965–) [A series of symposium proceedings of the International Congress on Flavins and Flavoproteins held every three years since their inception in 1965. No volume was published for the 1972 symposium.]
    book McCormick DB, Suttie JW and Wagner C (eds) (1997) Vitamins and coenzymes part I. Methods in Enzymology, vol. 279. San Diego: Academic Press.
    book McCormick DB, Suttie JW and Wagner C (eds) (1997) Vitamins and coenzymes part J. Methods in Enzymology, vol. 280. San Diego: Academic Press.
    book McCormick DB, Suttie JW and Wagner C (eds) (1997) Vitamins and coenzymes part K. Methods in Enzymology, vol. 281. San Diego: Academic Press.
    book McCormick DB and Wright LD (eds) (1970) Vitamins and coenzymes. Methods in Enzymology, vol. 18A. San Diego: Academic Press.
    book McCormick DB and Wright LD (eds) (1971) Vitamins and coenzymes. Methods in Enzymology, vols 18A and 18C. San Diego: Academic Press.
    book McCormick DB and Wright LD (eds) (1979) Vitamins and coenzymes part D. Methods in Enzymology, vol. 62. San Diego: Academic Press.
    book McCormick DB and Wright LD (eds) (1980) Vitamins and coenzymes part E. Methods in Enzymology, vol. 66. San Diego: Academic Press.
    book McCormick DB and Wright LD (eds) (1980) Vitamins and coenzymes part F. Methods in Enzymology, vol. 67. San Diego: Academic Press.
    book Müller F (1991) Chemistry and Biochemistry of Flavoenzymes, vol. 3. Boca Raton, FL: CRC Press.

Related Sub-Topics:

Proteins: Structure, Function, Metabolism | Other Biomolecules: Structure, Function, Metabolism | Enzymes: Structure and Action Mechanism
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Article Title: Flavin Coenzymes
 
How to Cite close
Ghisla, Sandro, and Edmondson, Dale E(Sep 2009) Flavin Coenzymes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000654.pub2]