1. Academic Validation
  2. Ophthalmic acid is a glutathione regulating tripeptide

Ophthalmic acid is a glutathione regulating tripeptide

  • FEBS J. 2024 Aug;291(15):3317-3330. doi: 10.1111/febs.17061.
Bauke V Schomakers 1 2 3 Sonia L Jillings 4 Michel van Weeghel 1 2 3 Frédéric M Vaz 1 2 3 Gajja S Salomons 1 2 Georges E Janssens 1 2 5 Riekelt H Houtkooper 1 2 5
Affiliations

Affiliations

  • 1 Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.
  • 2 Amsterdam Gastroenterology, Endocrinology, and Metabolism, The Netherlands.
  • 3 Core Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, The Netherlands.
  • 4 Green Biotechnology, Inholland University of Applied Sciences, Amsterdam, The Netherlands.
  • 5 Amsterdam Cardiovascular Sciences, The Netherlands.
Abstract

Since its discovery in 1958 in the lens of cows, ophthalmic acid (OPH) has stood in the shadow of its anti-oxidant analog: glutathione (GSH). Lacking the thiol group that gives GSH many of its important properties, ophthalmic acid's function has remained elusive, and it has been widely presumed to be an accidental product of the same Enzymes. In this review, we compile evidence demonstrating that OPH is a ubiquitous metabolite found in bacteria, Plants, fungi, and Animals, produced through several layers of metabolic regulation. We discuss the limitations of the oft-repeated suggestions that aberrations in OPH levels should solely indicate GSH deficiency or oxidative stress. Finally, we discuss the available literature and suggest OPH's role in metabolism as a GSH-regulating tripeptide; controlling both cellular and organelle influx and efflux of GSH, as well as modulating GSH-dependent reactions and signaling. Ultimately, we hope that this review reinvigorates and directs more research into this versatile metabolite.

Keywords

cellular metabolism; diabetes; glutathione; metabolomics; ophthalmate; ophthalmic acid; oxidative stress.

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