3-Indolepropionic acid: Difference between revisions

| verifiedrevid =

| IUPAC_name = <center>3-(1H-indol-3-yl)propanoic acid</center>

| tradename =Oxigon<ref name="IPA/Oxigon review">{{cite journal | vauthors = Bendheim PE, Poeggeler B, Neria E, Ziv V, Pappolla MA, Chain DG | title = Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease | journal = J. Mol. Neurosci. | volume = 19 | issue = 1-2 | pages = 213–7 | year = 2002 | pmid = 12212784 | doi = | quote = The accumulation of amyloid-beta and concomitant oxidative stress are major pathogenic events in Alzheimer's disease. Indole-3-propionic acid (IPA, OXIGON) is a potent anti-oxidant devoid of pro-oxidant activity. IPA has been demonstrated to be an inhibitor of beta-amyloid fibril formation and to be a potent neuroprotectant against a variety of oxidotoxins. This review will summarize the known properties of IPA and outline the rationale behind its selection as a potential disease-modifying therapy for Alzheimer's disease.}}</ref>

| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| legal_US_comment = Unscheduled

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment = Unscheduled

| elimination_half-life = Between 1–5&nbsp;hrs<ref name="Microbiome IPA review" />

| CAS_supplemental = <ref name="Human metabolome" />

| UNII =

| synonyms = Conjugate base:<br />Indole-3-propionate

| molecular_weight = 189.21054 g/mol

| melting_notes = <ref name="Human metabolome" />

'''3-Indolepropionic acid''' ('''IPA'''), or '''indole-3-propionic acid''', is a potent [[neuroprotective]] [[antioxidant]] and plant [[auxin]] that is being studied for therapeutic use in [[Alzheimer's disease]].<ref name="IPA/Oxigon review" /><ref name="Human metabolome" /><ref name="Microbiome IPA review" /> It is endogenously produced within the [[human microbiome]] and detectable in humans only when the bacteria ''[[Clostridium sporogenes]]'' is present in the gastrointestinal tract.<ref name="Microbiome IPA review">{{cite journal | vauthors = Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G | title = Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 10 | pages = 3698–703 | year = 2009 | pmid = 19234110 | pmc = 2656143 | doi = 10.1073/pnas.0812874106 | quote = Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes.&nbsp;... Conversely, a different set of enteric bacteria has been implicated in the metabolic transformation of indole to indole-3-propionic acid (IPA) (27). IPA, also identified only in the plasma of conv mice, has been shown to be a powerful antioxidant (28)&nbsp;... Although the presence of IPA in mammals has long been ascribed in the literature to bacterial metabolic processes, this conclusion was based on either the production of IPA in ex vivo cultures of individual bacterial species (31) or observed decreases in IPA levels in animals after administration of antibiotics (32). In our own survey of IPA production by representative members of the intestinal flora, only Clostridium sporogenes was found to produce IPA in culture (Table S2). Based on these results, individual GF mice were intentionally colonized with C. sporogenes strain ATCC 15579, and blood samples were taken at several intervals after colonization. IPA was undetectable in the samples taken shortly after introduction of the microbes, and was first observed in the serum 5 days after colonization, reaching plateau values comparable with conv mice by day 10. These colonization studies demonstrate that the introduction of enteric bacteria capable of IPA production in vivo into the gastrointestinal tract is sufficient to introduce IPA into the bloodstream of the host. Also, other GF animals were injected i.p. with either IPA (at 10, 20, or 40 mg/kg) or sterile PBS vehicle, and their serum concentrations of IPA were measured over time. As seen in Table S3, the high serum levels of IPA observed 1 h after injection decreased more than 90% within 5 h, showing that IPA is rapidly cleared from the blood, and that its presence in the serum of conv animals must result from continuous production from 1 or more bacterial species associated with the mammalian gut.}}<br />[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656143/figure/F2/ IPA metabolism diagram]</ref><ref name="C. sporogenes auxin synthesis">{{cite journal | vauthors = Attwood G, Li D, Pacheco D, Tavendale M | title = Production of indolic compounds by rumen bacteria isolated from grazing ruminants | journal = J. Appl. Microbiol. | volume = 100 | issue = 6 | pages = 1261–71 | year = 2006 | pmid = 16696673 | doi = 10.1111/j.1365-2672.2006.02896.x | url = }}</ref> In individuals who lack ''C. sporogenes'' colonization, IPA is not detectable in the blood.<ref name="Human metabolome" /><ref name="Microbiome IPA review" /> In other to synthesize IPA, ''C. sporogenes'' metabolizes [[tryptophan]] into [[indole]] and then subsequently 3-indolepropionic acid.<ref name="Microbiome IPA review" />

IPA is an even more potent scavenger of [[hydroxyl radical]]s than melatonin.<ref name="Human metabolome" /><ref name="Indolepropionic acid scavenging" /> Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.<ref name="Human metabolome">{{cite web|title=3-Indolepropionic acid|website=Human Metabolome Database|publisher=University of Alberta|accessdate=12 October 2015|url=http://www.hmdb.ca/metabolites/HMDB02302|quote=Indole-3-propionate (IPA), a deamination product of tryptophan formed by symbiotic bacteria in the gastrointestinal tract of mammals and birds. 3-Indolepropionic acid has been shown to prevent oxidative stress and death of primary neurons and neuroblastoma cells exposed to the amyloid beta-protein in the form of amyloid fibrils, one of the most prominent neuropathologic features of Alzheimer's disease. 3-Indolepropionic acid also shows a strong level of neuroprotection in two other paradigms of oxidative stress. (PMID: 10419516 )<br />Origin: {{bull}} Endogenous {{bull}} Microbial}}</ref><ref name="Indolepropionic acid scavenging">{{cite journal | vauthors = Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA | title = Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid | journal = J. Biol. Chem. | volume = 274 | issue = 31 | pages = 21937–42 | year = 1999 | pmid = 10419516 | doi = | quote = In the process of screening indole compounds for neuroprotection against Abeta, potent neuroprotective properties were uncovered for an endogenous related species, indole-3-propionic acid (IPA). This compound has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. IPA completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. T}}</ref><ref name="Melatonin intermediates">{{cite journal | vauthors = Reiter RJ, Guerrero JM, Garcia JJ, Acuña-Castroviejo D | title = Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin | journal = Ann. N. Y. Acad. Sci. | volume = 854 | issue = | pages = 410–24 | year = 1998 | pmid = 9928448 | doi = | url = }}</ref> ''C. sporogenes'' is the only bacteria known to synthesize 3-indolepropionic acid ''in vivo'' at levels which are subsequently detectable in the blood stream of the host.<ref name="Microbiome IPA review" /><ref name="C. sporogenes auxin synthesis">{{cite journal | vauthors = Attwood G, Li D, Pacheco D, Tavendale M | title = Production of indolic compounds by rumen bacteria isolated from grazing ruminants | journal = J. Appl. Microbiol. | volume = 100 | issue = 6 | pages = 1261–71 | year = 2006 | pmid = 16696673 | doi = 10.1111/j.1365-2672.2006.02896.x | url = }}</ref>

==References==

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