T3DB: Phenylacetic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (5)XML

Targets (5)

Record Information

Version

2.0

Creation Date

2014-08-29 05:47:14 UTC

Update Date

2014-12-24 20:26:40 UTC

Accession Number

T3D4153

Identification

Common Name

Phenylacetic acid

Class

Small Molecule

Description

Phenylacetic 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. Phenyl acetate (or phenylacetate) is a carboxylic acid ester that has been found in the biofluids of patients with nephritis and/or hepatitis as well as patients with phenylketonuria (PKU). Excess phenylalanine in the body can be disposed of through a transamination process leading to the production of phenylpyruvate. The phenylpyruvate can be further metabolized into a number of products. Decarboxylation of phenylpyruvate gives phenylacetate, while a reduction reaction gives phenyllactate. The phenylacetate can be further conjugated with glutamine to give phenylacetyl glutamine. All of these metabolites can be detected in serum and urine of PKU patients. Phenyl acetate is also produced endogenously as the metabolite of 2-Phenylethylamine, which is mainly metabolized by monoamine oxidase to form phenyl acetate. 2-phenylethylamine is an endogenous amphetamine which may modulate central adrenergic functions, and the urinary phenyl acetate levels have been postulated as a marker for depression. Phenylacetate is also found in essential oils, e.g. neroli, rose oil, free and as esters' and in many fruits. As a result it is used as a perfumery and flavoring ingredient. (1, 2, 3).

Compound Type

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

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2-Phenylacetate
2-Phenylacetic acid
2-Phenylethanoate
2-Phenylethanoic acid
a-Toluate
a-Toluic acid
alpha-Toluate
alpha-Toluic acid
Benzeneacetate
Benzeneacetic acid
Benzylformate
Benzylformic acid
Omega-Phenylacetate
Omega-Phenylacetic acid
Phenylacetate
Phenylethanoate
Phenylethanoic acid
w-Phenylacetate
w-Phenylacetic acid

Chemical Formula

C₈H₈O₂

Average Molecular Mass

136.148 g/mol

Monoisotopic Mass

136.052 g/mol

CAS Registry Number

103-82-2

IUPAC Name

2-phenylacetic acid

Traditional Name

ω-phenylacetic acid

SMILES

OC(=O)CC1=CC=CC=C1

InChI Identifier

InChI=1S/C8H8O2/c9-8(10)6-7-4-2-1-3-5-7/h1-5H,6H2,(H,9,10)

InChI Key

InChIKey=WLJVXDMOQOGPHL-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Not Available

Direct Parent

Benzene and substituted derivatives

Alternative Parents

Substituents

Monocyclic benzene moiety
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

monocarboxylic acid (CHEBI:30745 )
benzenes (CHEBI:30745 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	76.7°C
Boiling Point	265.5°C
Solubility	16.6 mg/mL
LogP	1.41

Predicted Properties

Property	Value	Source
Water Solubility	3.61 g/L	ALOGPS
logP	1.72	ALOGPS
logP	1.61	ChemAxon
logS	-1.6	ALOGPS
pKa (Strongest Acidic)	4.55	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	37.3 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	37.37 m³·mol⁻¹	ChemAxon
Polarizability	13.85 Å³	ChemAxon
Number of Rings	1	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-MS (1 TMS)	splash10-0006-9700000000-c07461cdad68959aa53f	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0006-9100000000-de65c7c0092343a4e599	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0006-9700000000-c07461cdad68959aa53f	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0006-9700000000-43e86e45beae2fa6704f	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0006-9200000000-dc43e5e062b0ed500c5f	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0006-9100000000-aaef76d181aebe492bbe	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 (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI M-80B) , Positive	splash10-0006-9100000000-de65c7c0092343a4e599	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , negative	splash10-0006-9000000000-6ca33b098558bf13801c	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-000i-0900000000-f898aafe4cecc87d26f1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0006-9400000000-aa5bff1d7a8df7c97bdb	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-014i-9000000000-6a017c8136a375269f3e	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-000i-2900000000-d79f9224f2390d6b17a2	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-0006-9000000000-e712b088c9a3d3855ec7	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-01ri-9000000000-f0ed89dae2c22d4c538c	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-053i-2900000000-3e4bf20b985893f203e7	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-000i-1900000000-5419b00a9c7c126093db	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-000i-1900000000-9a2e089c5511fa2bf210	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00kr-2900000000-94a6f40f937bf9d7e4c7	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0006-9500000000-8d3540e40bfc0e4c0e5f	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-417ad1f13a593ac780b9	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000l-5900000000-0ed04a623daaf32fffda	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000l-8900000000-709928d6b823240d3528	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00kf-9600000000-4a7739132344f3dec710	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-9000000000-5671d4c535a6553aaf0d	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-5671d4c535a6553aaf0d	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-5e37e9f4d7b24c763302	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00kf-9800000000-aacb25995ab02725e0f4	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0006-9100000000-930a2cbe3e9fb1915075	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00kf-9000000000-199de8006c0d100aaabb	2021-09-24	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0006-9100000000-1e23fd8e6ce900cd8e4c	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 125 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 15.09 MHz, CDCl₃, 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
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	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 phenylacetic 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) (5). 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 (6)

Metabolism

Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

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).

Minimum Risk Level

Not Available

Health Effects

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular 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

Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

30745

BioCyc ID

PHENYLACETATE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

PAC

ACToR ID

Not Available

Wikipedia Link

Phenylacetic_acid

References

Synthesis Reference

Zhou, Shu-jing; Li, Jin-lian; Luan, Fang. New synthetic method for benzeneacetic acid. Huaxue Yu Shengwu Gongcheng (2005), 22(2), 43-44.

MSDS

Link

General References

Ostergaard J, Larsen C: Bioreversible derivatives of phenol. 2. Reactivity of carbonate esters with fatty acid-like structures towards hydrolysis in aqueous solutions. Molecules. 2007 Oct 30;12(10):2396-412. [17978765 ]
Lorentz K, Flatter B, Augustin E: Arylesterase in serum: elaboration and clinical application of a fixed-incubation method. Clin Chem. 1979 Oct;25(10):1714-20. [476920 ]
Sabelli HC, Fawcett J, Gusovsky F, Javaid J, Edwards J, Jeffriess H: Urinary phenyl acetate: a diagnostic test for depression? Science. 1983 Jun 10;220(4602):1187-8. [6857245 ]
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 ]
Jankowski J, van der Giet M, Jankowski V, Schmidt S, Hemeier M, Mahn B, Giebing G, Tolle M, Luftmann H, Schluter H, Zidek W, Tepel M: Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. J Clin Invest. 2003 Jul;112(2):256-64. [12865413 ]
Pontoni G, Rotondo F, Spagnuolo G, Aurino MT, Carteni-Farina M, Zappia V, Lama G: Diagnosis and follow-up of cystinuria: use of proton magnetic resonance spectroscopy. Amino Acids. 2000;19(2):469-76. [11128553 ]
Rubin A, Knadler MP, Ho PP, Bechtol LD, Wolen RL: Stereoselective inversion of (R)-fenoprofen to (S)-fenoprofen in humans. J Pharm Sci. 1985 Jan;74(1):82-4. [3920382 ]
Davis BA, Kennedy SH, D'Souza J, Durden DA, Goldbloom DS, Boulton AA: Correlations of plasma and urinary phenylacetic acid and phenylethylamine concentrations with eating behavior and mood rating scores in brofaromine-treated women with bulimia nervosa. J Psychiatry Neurosci. 1994 Jul;19(4):282-8. [7918350 ]
Silvennoinen R, Malminiemi K, Malminiemi O, Seppala E, Vilpo J: Pharmacokinetics of chlorambucil in patients with chronic lymphocytic leukaemia: comparison of different days, cycles and doses. Pharmacol Toxicol. 2000 Nov;87(5):223-8. [11129502 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Aldose reductase

General Function:: Glyceraldehyde oxidoreductase activity
Specific Function:: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name:: AKR1B1
Uniprot ID:: P15121
Molecular Weight:: 35853.125 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	96 uM	Not Available	BindingDB 16419

References

Ferrari AM, Degliesposti G, Sgobba M, Rastelli G: Validation of an automated procedure for the prediction of relative free energies of binding on a set of aldose reductase inhibitors. Bioorg Med Chem. 2007 Dec 15;15(24):7865-77. Epub 2007 Aug 22. [17870536 ]
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. Tyrosine-protein kinase Lck

General Function:: Sh2 domain binding
Specific Function:: Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.
Gene Name:: LCK
Uniprot ID:: P06239
Molecular Weight:: 58000.15 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Dissociation	>50000 uM	Not Available	BindingDB 16419

References

Hajduk PJ, Zhou MM, Fesik SW: NMR-based discovery of phosphotyrosine mimetics that bind to the Lck SH2 domain. Bioorg Med Chem Lett. 1999 Aug 16;9(16):2403-6. [10476877 ]
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. 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

4. 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

5. 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 ]

Phenylacetic acid (T3D4153)

Structure for T3D4153: Phenylacetic acid

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

References

References

References