Proline metabolism and redox; maintaining a balance in health and disease

Lisa A Vettore, Rebecca L Westbrook, Daniel A Tennant

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Abstract

Proline is a non-essential amino acid with key roles in protein structure/function and maintenance of cellular redox homeostasis. It is available from dietary sources, generated de novo within cells, and released from protein structures; a noteworthy source being collagen. Its catabolism within cells can generate ATP and reactive oxygen species (ROS). Recent findings suggest that proline biosynthesis and catabolism are essential processes in disease; not only due to the role in new protein synthesis as part of pathogenic processes but also due to the impact of proline metabolism on the wider metabolic network through its significant role in redox homeostasis. This is particularly clear in cancer proliferation and metastatic outgrowth. Nevertheless, the precise identity of the drivers of cellular proline catabolism and biosynthesis, and the overall cost of maintaining appropriate balance is not currently known. In this review, we explore the major drivers of proline availability and consumption at a local and systemic level with a focus on cancer. Unraveling the main factors influencing proline metabolism in normal physiology and disease will shed light on new effective treatment strategies.

Original languageEnglish
Number of pages10
JournalAmino Acids
Early online date22 Jul 2021
DOIs
Publication statusE-pub ahead of print - 22 Jul 2021

Bibliographical note

Funding Information:
LAV is supported through Cancer Research UK Grant Number A26982, RLW is in part supported through Cancer Research UK Grant Number A24747.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Proline
  • Redox
  • Cancer
  • Disease

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