Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian Antimicrobial Metabolite

Annu Rev Nutr. 2015:35:451-73. doi: 10.1146/annurev-nutr-071714-034243. Epub 2015 May 13.

Abstract

Itaconic acid is well known as a precursor for polymer synthesis and has been involved in industrial processes for decades. In a recent surprising discovery, itaconic acid was found to play a role as an immune-supportive metabolite in mammalian immune cells, where it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. Although the immune-responsive gene 1 protein (IRG1) has been associated to immune response without a mechanistic function, the critical link to itaconic acid production through an enzymatic function of this protein was only recently revealed. In this review, we highlight the history of itaconic acid as an industrial and antimicrobial compound, starting with its biotechnological synthesis and ending with its antimicrobial function in mammalian immune cells.

Keywords: cis-aconitic acid decarboxylase; immune-responsive gene 1 protein (IRG1); inflammation; macrophage; metabolic immunity; metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism*
  • Aspergillus / metabolism
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Carboxy-Lyases
  • Citric Acid Cycle
  • Energy Metabolism / drug effects
  • Gene Expression
  • Glyoxylates / antagonists & inhibitors
  • Humans
  • Immune System
  • Inflammation
  • Malates / antagonists & inhibitors
  • Mammals
  • Proteins / analysis
  • Proteins / genetics
  • Proteins / physiology
  • Succinates / metabolism*
  • Succinates / pharmacology

Substances

  • Anti-Infective Agents
  • Glyoxylates
  • Malates
  • Proteins
  • Succinates
  • ACOD1 protein, human
  • Carboxy-Lyases
  • citramalate
  • glyoxylic acid
  • itaconic acid