Dissertation

Visualization of Vitamin A Metabolism

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

Author: Koenders, S.T.A.
Date: 17 September 2020
Links: Thesis in Leiden Repository

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system. Vitamin A is converted to retinoic acid (RA) by aldehyde dehydrogenases (ALDHs). The family of ALDHs consists of 19 members, three of which (ALDH1A1, ALDH1A2 andALDH1A3) have retinal as their preferred substrate. Due to a lack of selective and potent inhibitors for these enzymes, it is difficult to study their individual contribution to Vitamin A metabolism in biological systems.Therefore an activity-based probe based on the chemical structure of retinal has been synthesized to enable activity-based protein profiling (ABPP) of ALDHs. The probe covalently binds to the catalytic cysteine of ALDH enzymes which can then be visualized on gel or analyzed by proteomics using ligation chemistry.After biological evaluation of the probe this chemical tool has been used to study the influence of individual ALDH enzymes on the mucosal immune system and to determine the ALDH profile of several breast cancer cell lines. Thus showcasing its use to study Vitamin A metabolism in a wide variety of biological settings including but not limited to: immunology, cancer and (cancer) stem cells.