Amino Acid Chirality: Stereospecific Conversion and Physiological Implications

Area of Science:

• Biochemistry
• Enzymology
• Molecular Biology

Background:

• Chiral molecules, particularly amino acids, have distinct biological roles based on their absolute configuration (l- or d-).
• While proteins primarily use l-amino acids, d-amino acids are crucial in bacterial cell walls, neurotransmission, and metabolic pathways.
• The presence of both enantiomers necessitates stereoselective enzymes for their interconversion and recognition.

Purpose of the Study:

• To review the mechanistic insights into the interconversion of l- and d-amino acids by amino acid racemases.
• To discuss the structural, mechanistic, and evolutionary aspects of key enzymes involved in amino acid oxidative deamination.
• To highlight the physiological and pathological roles of specific d-amino acid enzymes and their potential as drug targets.

Main Methods:

• Literature review focusing on mechanistic studies of amino acid racemases.
• Analysis of structural, mechanistic, and evolutionary relationships of enzymes catalyzing amino acid interconversion.
• Examination of the physiological roles and implications of d-amino acid oxidase and d-aspartate oxidase.

Main Results:

• Amino acid racemases are key enzymes facilitating the interconversion of l- and d-amino acid enantiomers.
• Four crucial enzymes involved in oxidative deamination of amino acids exhibit distinct structural, mechanistic, and evolutionary characteristics.
• d-amino acid oxidase and d-aspartate oxidase have significant physiological implications in human health and disease.

Conclusions:

• Understanding amino acid racemase mechanisms is crucial for comprehending chiral molecule roles in biological systems.
• d-amino acid oxidase and d-aspartate oxidase represent potential therapeutic targets for various diseases.
• Microbially derived chiral-selective enzymes offer promising applications as biocatalysts in industrial processes.