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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2019-07-23 05:44:23 UTC
HMDB IDHMDB0000678
Secondary Accession Numbers
  • HMDB00678
Metabolite Identification
Common NameIsovalerylglycine
DescriptionIsovalerylglycine (IVG) is an acyl glycine. Acyl glycines are normally minor metabolites of fatty acids. However, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. In certain cases the measurement of these metabolites in body fluids can be used to diagnose disorders associated with mitochondrial fatty acid beta-oxidation. Acyl glycines are produced through the action of glycine N-acyltransferase (EC 2.3.1.13) which is an enzyme that catalyzes the chemical reaction: acyl-CoA + glycine < -- > CoA + N-acylglycine. Isovalerylglycine is a byproduct of the catabolism of the aminoacid leucine. Accumulation of isovalerylglycine occurs in Isovaleric Acidemia (IVA). IVA (OMIM/ McKusick 243500) is an autosomal recessive disorder caused by mutations in the isovaleryl-CoA dehydrogenase (EC 1.3.99.10) gene. The deficiency of this enzyme in the metabolism of leucine leads to the accumulation of a series of isovaleryl-CoA metabolites, such as isovalerylglycine. It is very important to caution for false positive results when screening for isovaleric acidemia by tandem mass spectrometry based on dried blood-spot levels of C5-acylcarnitines, including isovalerylcarnitine and its isomer, pivaloylcarnitine; pivaloylcarnitine is derived from pivalate-generating antibiotics, and has caused many false-positive results (PMID: 17850781 ). Isovalerylglycine is a biomarker for the consumption of cheese.
Structure
Data?1563860663
Synonyms
ValueSource
2-(3-Methylbutanoylamino)ethanoic acidChEBI
IsopentanoylglycineChEBI
N-IsopentanoylglycineChEBI
N-IsovaleroylglycineChEBI
2-(3-Methylbutanoylamino)ethanoateGenerator
3-MethylbutyrylglycineHMDB
N-Isovaleryl-glycineHMDB
[(3-Methylbutanoyl)amino]acetateHMDB
[(3-Methylbutanoyl)amino]acetic acidHMDB
IsovalerylglycineChEBI
Chemical FormulaC7H13NO3
Average Molecular Weight159.183
Monoisotopic Molecular Weight159.089543287
IUPAC Name2-(3-methylbutanamido)acetic acid
Traditional Nameisovalerylglycine
CAS Registry Number16284-60-9
SMILES
CC(C)CC(=O)NCC(O)=O
InChI Identifier
InChI=1S/C7H13NO3/c1-5(2)3-6(9)8-4-7(10)11/h5H,3-4H2,1-2H3,(H,8,9)(H,10,11)
InChI KeyZRQXMKMBBMNNQC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as n-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids
Alternative Parents
Substituents
  • N-acyl-alpha-amino acid
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Carbonyl group
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Biological location:

Source:

Process

Naturally occurring process:

Role

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point87 - 90 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.5 g/LALOGPS
logP0.35ALOGPS
logP0.1ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)4.17ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.4 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity39.22 m³·mol⁻¹ChemAxon
Polarizability16.4 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9200000000-30d4a8198b51e1741ecdJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-02mu-9400000000-7925a822e184ec8fe5b4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004r-9000000000-0a3d8ca5efe599736988JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-9000000000-bdd258e50d1f36946722JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-052f-9000000000-c69489d7cef77e37b417JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-7900000000-bdfe9288fa831ea12be2JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-9100000000-a536e4ad32d713ca358aJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-35336c548c7912945720JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1900000000-fad032ae217cd6458d13JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-7900000000-3c2abe9b7592a2477edbJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ab9-9000000000-762e4bed2c894348be25JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.17 +/- 0.03 uMNewborn (0-30 days old)BothNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.5925–7.1513 umol/mmol creatinineAdult (25-30 years old)Both
Not Available
details
UrineDetected and Quantified0.5424–5.6561 umol/mmol creatinineAdult (25-30 years old)Both
Not Available
details
UrineDetected and Quantified0.4771–4.7722 umol/mmol creatinineAdult (25-30 years old)Both
Not Available
details
UrineDetected and Quantified3.8 +/- 0.9 umol/mmol creatinineAdolescent (13-18 years old)FemaleNormal details
UrineDetected but not Quantified Adult (24-38years old)Not SpecifiedNormal details
UrineDetected and Quantified2.0 (0.4-4.0) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.37 +/- 1.19 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified2.322 +/- 1.914 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.213-10.157 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified<10 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified<1.15 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<14.205 umol/mmol creatinineChildren (1 - 13 years old)FemaleNormal details
UrineDetected and Quantified0 - 4.5 umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified40.0 (1.3-80.0) uMNewborn (0-30 days old)BothIsovaleric acidemia details
FecesDetected but not Quantified Adult (>18 years old)Both
Colorectal cancer
details
FecesDetected but not Quantified Adult (>18 years old)Both
Colorectal cancer
details
UrineDetected and Quantified15-195 umol/mmol creatinineAdolescent (13-18 years old)MaleIsovaleric acidemia
    • Isovaleric acidem...
details
UrineDetected and Quantified7.7 +/- 4.8 umol/mmol creatinineAdolescent (13-18 years old)FemaleAnorexia nervosa details
UrineDetected and Quantified2.813 +/- 2.181 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified0.0710-1.0654 umol/mmol creatinineInfant (0-1 year old)Not Specified2-Methylbutyryl-CoA dehydrogenase deficiency (SBACDD) details
UrineDetected and Quantified4538.509 umol/mmol creatinineNot SpecifiedNot SpecifiedIsovaleric acidemia details
UrineDetected and Quantified0.6 umol/mmol creatinineAdult (>18 years old)Not Specified
Propionic acidemia
details
UrineDetected and Quantified4474.586 umol/mmol creatinineChildren (1 - 13 years old)FemaleIsovaleric acidemia details
UrineDetected and Quantified3.4 - 36 umol/mmol creatinineAdolescent (13-18 years old)BothEthylmalonic encephalopathy details
UrineDetected and Quantified511.381-795.482 umol/mmol creatinineNewborn (0-30 days old)Not SpecifiedGlutaric Aciduria II details
Associated Disorders and Diseases
Disease References
Isovaleric acidemia
  1. Shigematsu Y, Hata I, Tanaka Y: Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia. Clin Chim Acta. 2007 Nov-Dec;386(1-2):82-6. Epub 2007 Aug 19. [PubMed:17850781 ]
  2. Krieger I, Tanaka K: Therapeutic effects of glycine in isovaleric acidemia. Pediatr Res. 1976 Jan;10(1):25-9. [PubMed:1246461 ]
  3. Matern D, He M, Berry SA, Rinaldo P, Whitley CB, Madsen PP, van Calcar SC, Lussky RC, Andresen BS, Wolff JA, Vockley J: Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. Pediatrics. 2003 Jul;112(1 Pt 1):74-8. [PubMed:12837870 ]
  4. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
  5. Yasutsugu Chinen, Sadao Nakamura, Kunihito Tamashiro, Osamu Sakamoto, Kyoko Tashiro, Takahiro Inokuchi, Koichi Nakanishi (2017). Isovaleric acidemia: Therapeutic response to supplementation with glycine, /react-text l react-text: 82 -carnitine, or both in combination and a 10-year. follow-up case study. Molecular Genetics and Metabolism Reports. Volume 11, June 2017, Pages 2-5. Molecular Genetics and Metabolism Reports.
Colorectal cancer
  1. Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016. [PubMed:27015276 ]
  2. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Anorexia nervosa
  1. Capo-chichi CD, Gueant JL, Lefebvre E, Bennani N, Lorentz E, Vidailhet C, Vidailhet M: Riboflavin and riboflavin-derived cofactors in adolescent girls with anorexia nervosa. Am J Clin Nutr. 1999 Apr;69(4):672-8. [PubMed:10197568 ]
Eosinophilic esophagitis
  1. (). Mordechai, Hien, and David S. Wishart. .
Propionic acidemia
  1. Riemersma M, Hazebroek MR, Helderman-van den Enden ATJM, Salomons GS, Ferdinandusse S, Brouwers MCGJ, van der Ploeg L, Heymans S, Glatz JFC, van den Wijngaard A, Krapels IPC, Bierau J, Brunner HG: Propionic acidemia as a cause of adult-onset dilated cardiomyopathy. Eur J Hum Genet. 2017 Nov;25(11):1195-1201. doi: 10.1038/ejhg.2017.127. Epub 2017 Aug 30. [PubMed:28853722 ]
Ethylmalonic encephalopathy
  1. Lehnert W, Ruitenbeek W: Ethylmalonic aciduria associated with progressive neurological disease and partial cytochrome c oxidase deficiency. J Inherit Metab Dis. 1993;16(3):557-9. [PubMed:7609451 ]
  2. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Glutaric aciduria II
  1. Gregersen N, Kolvraa S, Rasmussen K, Christensen E, Brandt NJ, Ebbesen F, Hansen FH: Biochemical studies in a patient with defects in the metabolism of acyl-CoA and sarcosine: another possible case of glutaric aciduria type II. J Inherit Metab Dis. 1980;3(3):67-72. [PubMed:6158623 ]
  2. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Short/branched chain acyl-CoA dehydrogenase deficiency
  1. Matern D, He M, Berry SA, Rinaldo P, Whitley CB, Madsen PP, van Calcar SC, Lussky RC, Andresen BS, Wolff JA, Vockley J: Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. Pediatrics. 2003 Jul;112(1 Pt 1):74-8. [PubMed:12837870 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022177
KNApSAcK IDNot Available
Chemspider ID475516
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID5647
PubChem Compound546304
PDB IDNot Available
ChEBI ID70984
References
Synthesis ReferenceBondi, S.; Eissler, F. Lipoproteins and the Fatty Degeneration of Cells. Biochemische Zeitschrift (1910), 23 499-513.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Fries MH, Rinaldo P, Schmidt-Sommerfeld E, Jurecki E, Packman S: Isovaleric acidemia: response to a leucine load after three weeks of supplementation with glycine, L-carnitine, and combined glycine-carnitine therapy. J Pediatr. 1996 Sep;129(3):449-52. [PubMed:8804338 ]
  2. Goodman SI, McCabe ER, Fennessey PV, Mace JW: Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II) with transient hypersarcosinemia and sarcosinuria; possible inherited deficiency of an electron transfer flavoprotein. Pediatr Res. 1980 Jan;14(1):12-7. [PubMed:7360517 ]
  3. Hine DG, Hack AM, Goodman SI, Tanaka K: Stable isotope dilution analysis of isovalerylglycine in amniotic fluid and urine and its application for the prenatal diagnosis of isovaleric acidemia. Pediatr Res. 1986 Mar;20(3):222-6. [PubMed:3703611 ]
  4. Shigematsu Y, Hata I, Tanaka Y: Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia. Clin Chim Acta. 2007 Nov-Dec;386(1-2):82-6. Epub 2007 Aug 19. [PubMed:17850781 ]

Enzymes

General function:
Involved in glycine N-acyltransferase activity
Specific function:
Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently. Can conjugate numerous substrates to form a variety of N-acylglycines, with a preference for benzoyl-CoA over phenylacetyl-CoA as acyl donors. Thereby detoxify xenobiotics, such as benzoic acid or salicylic acid, and endogenous organic acids, such as isovaleric acid.
Gene Name:
GLYAT
Uniprot ID:
Q6IB77
Molecular weight:
18506.33
General function:
Involved in glycine N-acyltransferase activity
Specific function:
Acyltransferase which transfers an acyl group to the N-terminus of glutamine. Can use phenylacetyl-CoA as an acyl donor.
Gene Name:
GLYATL1
Uniprot ID:
Q969I3
Molecular weight:
35100.895
General function:
Involved in glycine N-acyltransferase activity
Specific function:
Mitochondrial acyltransferase which transfers the acyl group to the N-terminus of glycine. Conjugates numerous substrates, such as arachidonoyl-CoA and saturated medium and long-chain acyl-CoAs ranging from chain-length C8:0-CoA to C18:0-CoA, to form a variety of N-acylglycines. Shows a preference for monounsaturated fatty acid oleoyl-CoA (C18:1-CoA) as an acyl donor. Does not exhibit any activity toward C22:6-CoA and chenodeoxycholoyl-CoA, nor toward serine or alanine.
Gene Name:
GLYATL2
Uniprot ID:
Q8WU03
Molecular weight:
34277.055
General function:
Involved in glycine N-acyltransferase activity
Specific function:
Acyltransferase which transfers the acyl group to the N- terminus of glycine
Gene Name:
GLYATL3
Uniprot ID:
Q5SZD4
Molecular weight:
32703.3