Characterization of endogenous D-amino acids in mammals via chiral separations

Lee, Cindy Jung

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https://hdl.handle.net/2142/115519 Copy

Description

Title

Characterization of endogenous D-amino acids in mammals via chiral separations

Author(s)

Lee, Cindy Jung

Issue Date

2022-04-08

Director of Research (if dissertation) or Advisor (if thesis)

Sweedler, Jonathan V

Doctoral Committee Chair(s)

Sweedler, Jonathan V

Committee Member(s)

• Dobrucki, Wawrzyniec
• Gewirth, Andrew A
• Rodríguez-López, Joaquín

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• D-amino acids
• Chiral Separations
• Capillary Electrophoresis
• Liquid Chromatography
• Mass Spectrometry

Abstract

Amino acids are one of the essential molecules for living organisms. Not only are amino acids required for vital processes such as building proteins and peptides, but they are also involved in cell-to-cell signaling. For a long time, it was believed that only L-amino acids were physiologically relevant molecules in mammals. However, diverse D-amino acids, the enantiomers of L-amino acids, have been detected in mammals with the aid of analytical advancements, and their biological significance, which differs from their L-enantiomers due to the chirality, has been studied. The distribution, origin, physiological relevance, and disease implications of D-amino acids have been gradually elucidated. For example, D-amino acids, like D-serine and D-aspartate, have been gaining research interest for their involvement in learning and memory. As a result, many current studies on D-amino acids are largely limited to the central nervous system. The knowledge of endogenous D-amino acids beyond the central nervous system, therefore, remains a mystery and requires further study to establish their metabolic pathways and functions. Nevertheless, studying the physiological and pathological function of D-amino acids in mammals requires sensitive and selective analytical determination of these low abundant and heterogeneously distributed molecules, while distinguishing them from higher concentrations of L-enantiomers based on chirality, in complex biological systems. Here, chiral separation techniques involving capillary electrophoresis-laser induced fluorescence and liquid chromatography-tandem mass spectrometry with methodological optimization are described to improve the quantitative characterization of D-amino acids in various tissues of mammals, including humans. Specifically, D-amino acids in cochlea, gut, more precisely gut microbiota, pancreatic islets, and serum are delineated to advance our understanding of these enigmatic cell-to-cell signaling molecules beyond the central nervous system.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Cindy Jung Lee

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