Distinctive roles of d-Amino acids in the homochiral world: Chirality of amino acids modulates mammalian physiology and pathology

Jumpei Sasabe, Masataka Suzuki

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Living organisms enantioselectively employ l-amino acids as the molecular architecture of protein synthesized in the ribosome. Although l-amino acids are dominantly utilized in most biological processes, accumulating evidence points to the distinctive roles of d-amino acids in non-ribosomal physiology. Among the three domains of life, bacteria have the greatest capacity to produce a wide variety of damino acids. In contrast, archaea and eukaryotes are thought generally to synthesize only two kinds of d-amino acids: d-serine and d-aspartate. In mammals, d-serine is critical for neurotransmission as an endogenous coagonist of N-methyl d-aspartate receptors. Additionally, d-aspartate is associated with neurogenesis and endocrine systems. Furthermore, recognition of d-amino acids originating in bacteria is linked to systemic and mucosal innate immunity. Among the roles played by d-amino acids in human pathology, the dysfunction of neurotransmission mediated by d-serine is implicated in psychiatric and neurological disorders. Non-enzymatic conversion of l-aspartate or l-serine residues to their d-configurations is involved in age-associated protein degeneration. Moreover, the measurement of plasma or urinary d-/l-serine or d-/l-aspartate levels may have diagnostic or prognostic value in the treatment of kidney diseases. This review aims to summarize current understanding of d-amino-acid-associated biology with a major focus on mammalian physiology and pathology.

Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalKeio Journal of Medicine
Volume68
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

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Keywords

  • Cell wall
  • Chirality
  • D-amino acid
  • Innate immunity
  • Neurobiology

ASJC Scopus subject areas

  • Medicine(all)

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