Cofactors

FAD.

Reaction Mechanism

L-amino-acid oxidase By Reference

L-aminoacid oxidase is a dimeric flavoprotein. it uses a non-covalently bound FAD cofactor in catalysing the stereospecific oxidative deamination of an L-amino acid substrate to an alpha ketoacid, forming ammonia and hydrogen peroxide. The enzyme shows a marked preference for hydrophobic amino acids including phenylalanine, tryptophan, tyrosine and leucine.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Products

The non-covalently bound FAD is first reduced to FADH2 with oxidation of the amino acid to an imino acid. Non-enzymatic hydrolysis at the imine centre leads to the elimination of ammonia and formation of an alpha-ketoacid. The mechanism is thought to involve a base for the abstraction of a proton from the amino group of the substrate and subsequent transfer of a hydride from the alpha carbon to the N5 of the isoalloxazine ring of FAD to form the imino intermediate.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
His	P81382	241	1f8r	223
Lys	P81382	344	1f8r	326

Step Components

overall reactant used, proton transfer, overall product formed, bimolecular nucleophilic addition, native state of cofactor regenerated, intermediate formation, aromatic bimolecular nucleophilic addition, hydride transfer, elimination (not covered by the Ingold mechanisms)



Step 1.

His223 acts as a base to deprotonate the amine group of the amino acid substrate.



Step 2.

Once depronated the substrate is activated for hydride transfer from the alpha-C atom to the N5 of FAD, forming the imine intermediate.



Step 3.

The presence of a structurally conserved water molecule and lysine residue suggest a possible role for Lys326 in activating the water for hydrolysis of the intermediate. The intermediate is subject to nucleophilic attack by the water, while the imine accepts a proton.



Step 4.

In an inferred hydrolysis step there is movement of electrons from the hydroxyl lone pair, causing elimination of ammonia and forming the product. Following hydrolysis there is an oxidative half reaction in which the cofactor FADH- is reoxidised to FAD by molecular oxygen.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• Analysis of inhibition mechanisms of Streptococcus agalactiae by Siganus oramin L‐amino acid oxidase
• Ancestral l-amino acid oxidase: From substrate scope exploration to phenylalanine ammonia-lyase assay.
• Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action.
• Red-spotted grouper Epinephelus akaara blood L-amino acid oxidase utilizes the substrates in plasma
• Substituted kynurenic acid derivatives as fluorophore-based probes for D- and L-amino acid oxidase assays and their in vitro application in eels.
• Co-Immobilization of a Multi-Enzyme Cascade: (S)-Selective Amine Transaminases, l-Amino Acid Oxidase and Catalase.
• Unveiling the peptidome diversity of Lachesismuta snake venom: Discovery of novel fragments of metalloproteinase, l-amino acid oxidase, and bradykinin potentiating peptides.
• Hydrogen peroxide from L-amino acid oxidase of king cobra (Ophiophagus hannah) venom attenuates Pseudomonas biofilms.
• Structural and functional analysis of hyper-thermostable ancestral L-amino acid oxidase that can convert Trp derivatives to D-forms by chemoenzymatic reaction.
• L-amino acid oxidase-1 is involved in the gut-liver axis by regulating 5-aminolevulinic acid production in mice.
• Purification of L-Amino acid oxidase obtained from Aspergillus terreus MZ769058 and its biochemical characterization