T3DB: Indoleacetic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (7)XML

Targets (7)

Record Information

Version

2.0

Creation Date

2014-08-29 05:47:06 UTC

Update Date

2014-12-24 20:26:40 UTC

Accession Number

T3D4152

Identification

Common Name

Indoleacetic acid

Class

Small Molecule

Description

Indoleacetic acid is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Indoleacetic acid (IAA) is a breakdown product of tryptophan metabolism and is often produced by the action of bacteria in the mammalian gut. Some endogenous production of IAA in mammalian tissues also occurs. It may be produced by the decarboxylation of tryptamine or the oxidative deamination of tryptophan. IAA frequently occurs at low levels in urine and has been found in elevated levels in the urine of patients with phenylketonuria ( Using material extracted from human urine, it was discovered by Kogl in 1933 that Indoleacetic acid is also an important plant hormone Specifically IAA is a member of the group of phytohormones called auxins. IAA is generally considered to be the most important native auxin. Plant cells synthesize IAA from tryptophan. IAA and some derivatives can be oxidised by horseradish peroxidase (HRP) to cytotoxic species. IAA is only toxic after oxidative decarboxylation; the effect of IAA/HRP is thought to be due in part to the formation of methylene-oxindole, which may conjugate with DNA bases and protein thiols. IAA/HRP could be used as the basis for targeted cancer therapy involving antibody-, polymer-, or gene-directed approaches, a potential new role for plant auxins in cancer therapy. (1, 2).

Compound Type

Food Toxin
Industrial/Workplace Toxin
Lachrymator
Metabolite
Natural Compound
Organic Compound
Uremic Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(1H-Indol-3-yl)-acetate
(1H-Indol-3-yl)-acetic acid
1H-Indol-3-ylacetate
1H-Indol-3-ylacetic acid
1H-Indole-3-acetate
1H-Indole-3-acetic acid
2-(1H-Indol-3-yl)acetate
2-(1H-Indol-3-yl)acetic acid
2-(3-Indolyl)acetate
2-(3-Indolyl)acetic acid
3-(Carboxymethyl)indole
3-IAA
3-Indole-Acetic acid
3-Indoleacetate
3-Indoleacetic acid
3-Indolylacetate
3-Indolylacetic acid
alpha-Indol-3-yl-acetic acid
b-Indoleacetate
b-Indoleacetic acid
b-Indolylacetate
b-Indolylacetic acid
beta-Indole-3-acetic acid
beta-Indoleacetate
beta-Indoleacetic acid
beta-Indolylacetate
beta-Indolylacetic acid
Heteroauxin
Indol-3-ylacetate
Indol-3-ylacetic acid
Indole-3-acetate
Indole-3-acetic acid
Indoleacetate
Indolyl-3-acetate
Indolyl-3-acetic acid
Indolylacetate
Indolylacetic acid
Kyselina 3-indolyloctova
Rhizopin
Rhizopon A
Skatole carboxylate
Skatole carboxylic acid

Chemical Formula

C₁₀H₉NO₂

Average Molecular Mass

175.184 g/mol

Monoisotopic Mass

175.063 g/mol

CAS Registry Number

87-51-4

IUPAC Name

2-(1H-indol-3-yl)acetic acid

Traditional Name

β-indole-3-acetic acid

SMILES

OC(=O)CC1=CNC2=CC=CC=C12

InChI Identifier

InChI=1S/C10H9NO2/c12-10(13)5-7-6-11-9-4-2-1-3-8(7)9/h1-4,6,11H,5H2,(H,12,13)

InChI Key

InChIKey=SEOVTRFCIGRIMH-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as indole-3-acetic acid derivatives. Indole-3-acetic acid derivatives are compounds containing an acetic acid (or a derivative) linked to the C3 carbon atom of an indole.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indoles and derivatives

Sub Class

Indolyl carboxylic acids and derivatives

Direct Parent

Indole-3-acetic acid derivatives

Alternative Parents

Substituents

Indole-3-acetic acid derivative
3-alkylindole
Indole
Substituted pyrrole
Benzenoid
Heteroaromatic compound
Pyrrole
Azacycle
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Carbonyl group
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Organic nitrogen compound
Hydrocarbon derivative
Organic oxide
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

monocarboxylic acid (CHEBI:16411 )
indole-3-acetic acids (CHEBI:16411 )
Indole alkaloids (C00954 )
Auxins (C00954 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

Brain
Central Nervous System
Fibroblasts
Hippocampus
Hypothalamus
Kidney
Liver
Platelet
Spinal Cord
Striatum

Pathways

Name	SMPDB Link	KEGG Link
Tryptophan Metabolism	SMP00063	map00380
Hartnup Disorder	SMP00189	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	168.5°C
Boiling Point	Not Available
Solubility	1.5 mg/mL
LogP	1.41

Predicted Properties

Property	Value	Source
Water Solubility	1.38 g/L	ALOGPS
logP	1.87	ALOGPS
logP	1.71	ChemAxon
logS	-2.1	ALOGPS
pKa (Strongest Acidic)	4.66	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	53.09 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	48.45 m³·mol⁻¹	ChemAxon
Polarizability	17.74 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0udi-0391000000-7581f14fe5be5b2b2954	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0udi-0691000000-de9ac4f748d50db109ea	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0udi-0591000000-9687f83d1372abe23c3c	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0udi-1793100000-7c78003038436ec5a902	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)	splash10-00ai-7910000000-4aa7b8244f32048c76bc	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0fk9-9250000000-a5f931fc3292056dba65	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (1 TMS)	splash10-001i-1920000000-f0ecee61454a589493af	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0udi-1692000000-ce863a1ca2a657cb41d5	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-003r-0900000000-1edcb4977a52155bc130	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0391000000-7581f14fe5be5b2b2954	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0691000000-de9ac4f748d50db109ea	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0591000000-9687f83d1372abe23c3c	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-1793100000-7c78003038436ec5a902	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00ai-7910000000-4aa7b8244f32048c76bc	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0fk9-9250000000-a5f931fc3292056dba65	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-001i-1920000000-f0ecee61454a589493af	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0udi-1692000000-ce863a1ca2a657cb41d5	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0691000000-f6073f8f35a6930b5aac	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0059-1900000000-ab74ec83b16ac0b97d12	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-001i-7920000000-8dab2ad22251c9fbd21c	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-004i-0900000000-f6dbb01a35af3042d126	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-004i-0900000000-2ae231b7d0e2cd50aed8	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-004i-6900000000-9eae14faa16b8f8259da	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positive	splash10-003r-0900000000-1edcb4977a52155bc130	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-00e9-0900000000-187b48f2258823cbc6a2	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-001i-0900000000-30b7a73fa446d0e3c8d3	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-004i-0900000000-bbe0fb5a48f89ea6e383	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-004i-0900000000-97850f400d80de278334	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-004i-0900000000-600545759ef108827b9e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-0kxr-5900000000-ba2eed29832f9ee48921	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-004l-5900000000-a0b30710f83e53b6f3db	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-001i-9500000000-146ac0a20f9d53e76291	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-053r-9600000000-d9258b3c6b5c6f748f6e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-004i-9300000000-b59628beb41b424daf4a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (UPLC Waters, Quattro Ultima Pt Micromass) , Positive (Annotated)	splash10-004i-0900000000-755373c9248cfb6425fc	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-004i-0900000000-2b3df7a1dd85faea6705	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positive	splash10-003r-0900000000-9522ab089ab89b64f96a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-001i-0900000000-b735e95cb23091491c2e	2012-08-31	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0900000000-2a3dd24f136523e6ce1e	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-053r-0900000000-77436493836245345cb8	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00lr-1900000000-4e0b6f24d03c0b25800f	2015-04-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00e9-0900000000-1d045a56f3669a1c9391	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-05ai-0900000000-518778c36bacbf77b901	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a5c-3900000000-323fc64084836756be30	2015-04-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0900000000-2a3dd24f136523e6ce1e	2015-05-27	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-1900000000-3ffc47eb6c977956ad93	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 15.09 MHz, DMSO-d6, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹H NMR Spectrum (1D, D₂O, experimental)	Not Available	2016-10-22	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, D₂O, experimental)	Not Available	2016-10-22	View Spectrum
2D NMR	[¹H, ¹H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)	Not Available	2012-12-04	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Endogenous, Ingestion, Dermal (contact)

Mechanism of Toxicity

Uremic toxins such as indole-3-acetic acid are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (4). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (5)

Metabolism

Indoleacetic acid (IAA) is a breakdown product of tryptophan metabolism and is often produced by the action of bacteria in the mammalian gut. Some endogenous production of IAA in mammalian tissues also occurs. It may be produced by the decarboxylation of tryptamine or the oxidative deamination of tryptophan.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Naturally produced by the body (endogenous). Also a plant growth hormone (auxin).

Minimum Risk Level

Not Available

Health Effects

Indoleacetic acid is listed in its MSDS as potentially mutagenic to mammalian somatic cells. It is also identified as a potential skin, eye, and respiratory irritant, and users are warned not to ingest it. Acute exposure to Indoleacetic acid can lead to some mild skin and eye irritation. Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Chronically high levels of Indoleacetic acid are associated with the inborn error of metabolism known as Hartnup disease.

Symptoms

As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

Treatment

Chronic Exposure: Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored. Acute Exposure: EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice.

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

16411

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

IAC

ACToR ID

Not Available

Wikipedia Link

Indoleacetic acid

References

Synthesis Reference

Not Available

MSDS

Link

General References

WEISSBACH H, KING W, SJOERDSMA A, UDENFRIEND S: Formation of indole-3-acetic acid and tryptamine in animals: a method for estimation of indole-3-acetic acid in tissues. J Biol Chem. 1959 Jan;234(1):81-6. [13610897 ]
Folkes LK, Wardman P: Oxidative activation of indole-3-acetic acids to cytotoxic species- a potential new role for plant auxins in cancer therapy. Biochem Pharmacol. 2001 Jan 15;61(2):129-36. [11163327 ]
Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [22626821 ]
Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Carpenter LL, Anderson GM, Siniscalchi JM, Chappell PB, Price LH: Acute changes in cerebrospinal fluid 5-HIAA following oral paroxetine challenge in healthy humans. Neuropsychopharmacology. 2003 Feb;28(2):339-47. [12589387 ]
Owens MJ, Nemeroff CB: Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 1994 Feb;40(2):288-95. [7508830 ]
Tu JB, Wong CY: Serotonin metabolism in normal and abnormal infants during the perinatal period. Biol Neonate. 1976;29(3-4):187-93. [133735 ]
Blennow K, Wallin A, Gottfries CG, Mansson JE, Svennerholm L: Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid. J Neural Transm Park Dis Dement Sect. 1993;5(1):5-15. [7679905 ]
Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. [8087979 ]
Morgan WW, Grant RW: Increased rate of disappearance of serum probenecid in barbital dependent rats. Eur J Pharmacol. 1976 Dec;40(2):349-57. [1033074 ]
Jellinger K, Riederer P: Brain monoamines in metabolic (endotoxic) coma. A preliminary biochemical study in human postmortem material. J Neural Transm. 1977;41(4):275-86. [925688 ]
Sarrias MJ, Cabre P, Martinez E, Artigas F: Relationship between serotoninergic measures in blood and cerebrospinal fluid simultaneously obtained in humans. J Neurochem. 1990 Mar;54(3):783-6. [1689378 ]
Kema IP, Meijer WG, Meiborg G, Ooms B, Willemse PH, de Vries EG: Profiling of tryptophan-related plasma indoles in patients with carcinoid tumors by automated, on-line, solid-phase extraction and HPLC with fluorescence detection. Clin Chem. 2001 Oct;47(10):1811-20. [11568091 ]
Bai F, Jones DC, Lau SS, Monks TJ: Serotonergic neurotoxicity of 3,4-(+/-)-methylenedioxyamphetamine and 3,4-(+/-)-methylendioxymethamphetamine (ecstasy) is potentiated by inhibition of gamma-glutamyl transpeptidase. Chem Res Toxicol. 2001 Jul;14(7):863-70. [11453733 ]
Ridges AP, Bishop FM, Lawton K, Goldberg IJ: Amine metabolism, thyroid function and response to clomipramine and maprotiline medication in depression. Postgrad Med J. 1980;56 Suppl 1:37-41. [6156444 ]
Raghuram TC, Krishnaswamy K: Serotonin metabolism is pellagra. Arch Neurol. 1975 Oct;32(10):708-10. [1180737 ]
Carling RS, Degg TJ, Allen KR, Bax ND, Barth JH: Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem. 2002 Nov;39(Pt 6):577-82. [12564839 ]
Taniguchi K, Okatani Y, Sagara Y: Serotonin metabolism in the fetus in preeclampsia. Asia Oceania J Obstet Gynaecol. 1994 Mar;20(1):77-86. [7513511 ]
Russo S, Boon JC, Kema IP, Willemse PH, den Boer JA, Korf J, de Vries EG: Patients with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulation. Psychosom Med. 2004 May-Jun;66(3):422-5. [15184706 ]
Igari T, Shimamura T: Serotonin metabolism and its enzymic activities in joint diseases. Clin Orthop Relat Res. 1979 Mar-Apr;(139):232-49. [455840 ]
Bearcroft CP, Perrett D, Farthing MJ: Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study. Gut. 1998 Jan;42(1):42-6. [9505884 ]
Ilkhanizadeh B, Owji AA, Tavangar SM, Vasei M, Tabei SM: Spot urine 5-hydroxy indole acetic acid and acute appendicitis. Hepatogastroenterology. 2001 May-Jun;48(39):609-13. [11462886 ]
Igari T, Tsuchizawa M, Shimamura T: Alteration of tryptophan metabolism in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. Tohoku J Exp Med. 1987 Oct;153(2):79-86. [3500530 ]
Apak S, Kazez A, Ozel SK, Ustundag B, Akpolat N, Kizirgil A: Spot urine 5-hydroxyindoleacetic acid levels in the early diagnosis of acute appendicitis. J Pediatr Surg. 2005 Sep;40(9):1436-9. [16150345 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Group IIE secretory phospholipase A2

General Function:: Phospholipase a2 activity
Specific Function:: PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a preference for arachidonic-containing phospholipids.
Gene Name:: PLA2G2E
Uniprot ID:: Q9NZK7
Molecular Weight:: 15988.525 Da

References

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

Target Details

2. Kynurenine--oxoglutarate transaminase 1

General Function:: Transaminase activity
Specific Function:: Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond.
Gene Name:: CCBL1
Uniprot ID:: Q16773
Molecular Weight:: 47874.765 Da

References

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

Target Details

3. S-phase kinase-associated protein 1

General Function:: Ubiquitin-protein transferase activity
Specific Function:: Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2 (PubMed:25704143). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2.
Gene Name:: SKP1
Uniprot ID:: P63208
Molecular Weight:: 18657.86 Da

References

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

Target Details

4. Klotho

General Function:: Vitamin d binding
Specific Function:: May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Gene Name:: KL
Uniprot ID:: Q9UEF7
Molecular Weight:: 116179.815 Da

References

Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

Target Details

5. NADPH oxidase 4

General Function:: Superoxide-generating nadph oxidase activity
Specific Function:: Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
Gene Name:: NOX4
Uniprot ID:: Q9NPH5
Molecular Weight:: 66930.995 Da

References

Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

Target Details

6. Solute carrier family 22 member 8

General Function:: Sodium-independent organic anion transmembrane transporter activity
Specific Function:: Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:: SLC22A8
Uniprot ID:: Q8TCC7
Molecular Weight:: 59855.585 Da

References

Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

Target Details

7. Transient receptor potential cation channel subfamily A member 1

General Function:: Temperature-gated cation channel activity
Specific Function:: Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:: TRPA1
Uniprot ID:: O75762
Molecular Weight:: 127499.88 Da

References

Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]

Indoleacetic acid (T3D4152)

Structure for T3D4152: Indoleacetic acid

Targets

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