DAAO Human

D-Amino Acid Oxidase (DAAO) is a flavoenzyme that catalyzes the oxidative deamination of D-amino acids, converting them into their corresponding α-keto acids, ammonia, and hydrogen peroxide . This enzyme is highly specific for D-amino acids, excluding acidic ones, and plays a crucial role in various physiological processes, particularly in the central nervous system .

DAAO was first discovered in 1935 by Hans Adolf Krebs during experiments with porcine kidney homogenates and amino acids . Shortly after its discovery, Warburg and Christian identified the presence of a flavin adenine dinucleotide (FAD) cofactor, making DAAO the second flavoenzyme to be discovered . Over the years, DAAO has been extensively studied, leading to a deeper understanding of its structure, function, and regulation .

DAAO is a homodimeric enzyme, with each monomer containing an FAD-binding domain and a substrate-binding domain . The enzyme’s three-dimensional structure is highly conserved across different species, with minor variations that account for functional differences . In humans, DAAO is primarily involved in the degradation of D-serine, a neuromodulator that acts as a coagonist of N-methyl D-aspartate (NMDA) receptors . These receptors are critical for various brain functions and are implicated in several neurological disorders .

Recombinant human DAAO is typically expressed in Escherichia coli and isolated as an active homodimeric flavoenzyme . This recombinant form retains the properties of the native enzyme, including its low kinetic efficiency and sequential kinetic mechanism . The recombinant enzyme is valuable for research and biotechnological applications, providing insights into the enzyme’s function and potential therapeutic uses .

DAAO’s activity must be finely tuned to maintain physiological functions, particularly in the brain where it regulates D-serine levels . The enzyme’s role extends beyond the central nervous system, contributing to detoxification processes and energy generation in microorganisms . In biotechnology, DAAO is used in biocatalysis to produce α-keto acids from D-amino acids, resolve racemic mixtures, and in cancer therapy .

Recent studies focus on the epigenetic modulation of DAAO expression and the impact of post-translational modifications on its biochemical properties . Additionally, the enzyme’s link to neurological disorders, such as schizophrenia, is being explored, with inhibitors like risperidone and sodium benzoate showing potential therapeutic benefits .