3-Indolepropionic acid

IPA is an even more potent scavenger of hydroxyl radicals than melatonin, the most potent scavenger of hydroxyl radicals that is synthesized by human enzymes. Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.

Occurrence

Biosynthesis in humans and cellular effects

This compound is endogenously produced by human microbiota and has only been detected in vivo when the species Clostridium sporogenes is present in the gastrointestinal tract. As of April 2016, C. sporogenes, which uses tryptophan to synthesize IPA, is the only species of bacteria known to synthesize IPA in vivo at levels which are subsequently detectable in the blood plasma of the host.

C. sporogenes produces IPA via a two step process. Tryptophanase (TnaA) first converts tryptophan into indole. Tryptophan amino transferase (Tam1) then converts indole into IPA.

Peptostreptococcus species with a full fldAIBC gene cluster convert tryptophan into IPA and 3-indoleacrylic acid (IA) in vitro and protects against colitis in mice. IA differs from IPA only by a double bond and both enhance IL-10 secretion after LPS stimulation. However, IA does not reduce TNF production after LPS stimulation. It also activates the NRF2 antioxidant pathway and induces the expression of AhR target genes, unlike IPA.

Biosynthesis by soil microbes

IPA is structurally similar to the phytohormone auxin (indole-3-acetic acid, IAA). Plants may encounter the substance when soil bacteria that produces IPA is present (Clostridium is known to reside in soil). Like auxin, IPA increases the growth of lateral roots and root hairs. However, it seems to inhibit some auxin-related processes such as root gravitation, probably by interfering with the plant's own auxin signaling and/or transport.