Flavin Monoxygenases

 

 

 

yucca reveals an unlikely pathway to auxin biosynthesis Mammalian FMOs have been well-characterized biochemically, but little is known about their physiological roles. Recently research identified a FMO that upregulates IAA synthesis through the "mysterious third pathway." They proposed, based on biochemical assays, that IAA synthesis occur through tryptamine by the hydroxylation of a FMO (Zhao et al 2001).

 

Flavin monooxygenases: Flavin nucleotides are diverse molecules depending on their surrounding protein environments. They have a role in many different reduction reactions. Flavin monooxygenases, like the P450 enzymes, are found in the endoplasmic reticulum. However, they are mechanistically distinct from the P450's, reacting with oxygen and NADPH in the absence of substrate to form a 4a-hydroperoxy flavin enzyme intermediate. The 4-hydroperoxy flavin form is extremely reactive. Thus, FMOs exist in an activated form in the cell, that interacts with a nucleophilic group (such as an amine, thiol, or phosphate), to complete the catalytic cycle. All that is required for product formation at this point is contact between the substrate and the terminal oxygen of the 4-hydroperoxy flavin. The capacity of FMOS to remain stable while poised in an activated state may explain the broad substrate specificity of the FMO isozymes (Figure 16) (Ziegler 1993).

 

Figure 16: Major steps in the catalytic cycle of FMO. Oxygenated product (SO) is formed by nucleophilic attack of oxygenatable substrate (S) on the terminal oxygen of the enzyme-bound hydroperoxyflavin followed by heterlytic cleavage of the peroxide (1). The release of the H2O (2) or of NADP+ (3) is rate-limiting for FMOs. Reductions of flavin by NADPH (4) and addition of oxygen (5) complete the catalytic cycle by regenerating the oxygenating intermdediate (Ziegler 1990).

 

FMO reaction: FMOs catalyze oxidation of organic compounds by molecular oxygen using NADPH as an electron source for reduction of one of the oxygen atoms (Figure 17) (Panvera 2001).

RH + O2 + NADPH + H+ --- FMO---> ROH + H2O + NADP+

 Figure 17: FMO catalyze the oxidation of organic compounds

Common characteristics of all FMOs: A functional FMO must have FAD and NADPH binding motifs (Ziegler 1990).

 

Home Page	Introduction
Plant Hormones	Auxins
yucca	Flavin Monooxygenase
Conclusion	References