MiMeDB: Showing metabocard for N-Acetylisoleucine (MMDBc0000678)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:52:33 UTC

Update Date

2024-04-30 19:33:30 UTC

Metabolite ID

MMDBc0000678

Metabolite Identification

Common Name

N-Acetylisoleucine

Description

N-Acetyl-L-isoleucine or N-Acetylisoleucine, 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. N-Acetylisoleucine can also be classified as an alpha amino acid or a derivatized alpha amino acid. Technically, N-Acetylisoleucine is a biologically available N-terminal capped form of the proteinogenic alpha amino acid L-isolecuine. N-acetyl amino acids can be produced either via direct synthesis of specific N-acetyltransferases or via the proteolytic degradation of N-acetylated proteins by specific hydrolases. N-terminal acetylation of proteins is a widespread and highly conserved process in eukaryotes that is involved in protection and stability of proteins (PMID: 16465618 ). About 85% of all human proteins and 68% of all yeast proteins are acetylated at their N-terminus (PMID: 21750686 ). Several proteins from prokaryotes and archaea are also modified by N-terminal acetylation. The majority of eukaryotic N-terminal-acetylation reactions occur through N-acetyltransferase enzymes or NAT‚Äôs (PMID: 30054468 ). These enzymes consist of three main oligomeric complexes NatA, NatB, and NatC, which are composed of at least a unique catalytic subunit and one unique ribosomal anchor. The substrate specificities of different NAT enzymes are mainly determined by the identities of the first two N-terminal residues of the target protein. The human NatA complex co-translationally acetylates N-termini that bear a small amino acid (A, S, T, C, and occasionally V and G) (PMID: 30054468 ). NatA also exists in a monomeric state and can post-translationally acetylate acidic N-termini residues (D-, E-). NatB and NatC acetylate N-terminal methionine with further specificity determined by the identity of the second amino acid. N-acetylated amino acids, such as N-acetylisoleucine can be released by an N-acylpeptide hydrolase from peptides generated by proteolytic degradation (PMID: 16465618 ). In addition to the NAT enzymes and protein-based acetylation, N-acetylation of free isoleucine can also occur. In particular, N-Acetylisoleucine can be biosynthesized from L-isoleucine and acetyl-CoA by the enzyme leucine/isoleucine N-acetyltransferase (EC 2.3.1.66). Excessive amounts N-acetyl amino acids including N-acetylisoleucine (as well as N-acetylglycine, N-acetylserine, N-acetylglutamine, N-acetylglutamate, N-acetylalanine, N-acetylmethionine and smaller amounts of N-acetylthreonine, N-acetylleucine, and N-acetylvaline) can be detected in the urine with individuals with acylase I deficiency, a genetic disorder (PMID: 16465618 ). Aminoacylase I is a soluble homodimeric zinc binding enzyme that catalyzes the formation of free aliphatic amino acids from N-acetylated precursors. In humans, Aminoacylase I is encoded by the aminoacylase 1 gene (ACY1) on chromosome 3p21 that consists of 15 exons (OMIM 609924 ). Individuals with aminoacylase I deficiency will experience convulsions, hearing loss and difficulty feeding (PMID: 16465618 ). ACY1 can also catalyze the reverse reaction, the synthesis of acetylated amino acids. Many N-acetylamino acids, including N-acetylisoleucine are classified as uremic toxins if present in high abundance in the serum or plasma (PMID: 26317986 ; PMID: 20613759 ). Uremic toxins are a diverse group of endogenously produced molecules that, if not properly cleared or eliminated by the kidneys, can cause kidney damage, cardiovascular disease and neurological deficits (PMID: 18287557 ).

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HEADER    PROTEIN                                 08-MAR-19   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   08-MAR-19         0                                  
HETATM    1  C   UNK     0    8667.3338665.899   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0    8666.0008665.127   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0    8664.6678665.899   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0    8663.3338665.127   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0    8666.0008663.587   0.000  0.00  0.00           C+0
HETATM    6  N   UNK     0    8667.3338667.436   0.000  0.00  0.00           N+0
HETATM    7  C   UNK     0    8668.6688668.206   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0    8670.0008667.436   0.000  0.00  0.00           C+0
HETATM    9  O   UNK     0    8668.6688669.746   0.000  0.00  0.00           O+0
HETATM   10  C   UNK     0    8668.6688665.127   0.000  0.00  0.00           C+0
HETATM   11  O   UNK     0    8670.0008665.899   0.000  0.00  0.00           O+0
HETATM   12  O   UNK     0    8668.6688663.587   0.000  0.00  0.00           O+0
CONECT    1    2    6   10                                                  
CONECT    2    1    3    5                                                  
CONECT    3    2    4                                                       
CONECT    4    3                                                            
CONECT    5    2                                                            
CONECT    6    1    7                                                       
CONECT    7    6    8    9                                                  
CONECT    8    7                                                            
CONECT    9    7                                                            
CONECT   10    1   11   12                                                  
CONECT   11   10                                                            
CONECT   12   10                                                            
MASTER        0    0    0    0    0    0    0    0   12    0   22    0
END

COMPND    HMDB0061684
HETATM    1  C1  UNL     1      -3.233   0.054   0.451  1.00  0.00           C  
HETATM    2  C2  UNL     1      -2.006  -0.797   0.144  1.00  0.00           C  
HETATM    3  C3  UNL     1      -0.814   0.102  -0.041  1.00  0.00           C  
HETATM    4  C4  UNL     1      -1.004   1.077  -1.175  1.00  0.00           C  
HETATM    5  C5  UNL     1       0.467  -0.657  -0.139  1.00  0.00           C  
HETATM    6  N1  UNL     1       1.532   0.321  -0.314  1.00  0.00           N  
HETATM    7  C6  UNL     1       2.556   0.498   0.651  1.00  0.00           C  
HETATM    8  C7  UNL     1       3.605   1.511   0.405  1.00  0.00           C  
HETATM    9  O1  UNL     1       2.592  -0.186   1.710  1.00  0.00           O  
HETATM   10  C8  UNL     1       0.495  -1.695  -1.180  1.00  0.00           C  
HETATM   11  O2  UNL     1       1.366  -1.682  -2.095  1.00  0.00           O  
HETATM   12  O3  UNL     1      -0.421  -2.734  -1.212  1.00  0.00           O  
HETATM   13  H1  UNL     1      -4.108  -0.247  -0.161  1.00  0.00           H  
HETATM   14  H2  UNL     1      -3.479  -0.087   1.537  1.00  0.00           H  
HETATM   15  H3  UNL     1      -3.046   1.129   0.308  1.00  0.00           H  
HETATM   16  H4  UNL     1      -2.253  -1.355  -0.798  1.00  0.00           H  
HETATM   17  H5  UNL     1      -1.799  -1.485   0.983  1.00  0.00           H  
HETATM   18  H6  UNL     1      -0.746   0.716   0.906  1.00  0.00           H  
HETATM   19  H7  UNL     1      -0.739   2.111  -0.923  1.00  0.00           H  
HETATM   20  H8  UNL     1      -0.350   0.750  -2.021  1.00  0.00           H  
HETATM   21  H9  UNL     1      -2.082   0.992  -1.484  1.00  0.00           H  
HETATM   22  H10 UNL     1       0.650  -1.168   0.837  1.00  0.00           H  
HETATM   23  H11 UNL     1       1.506   0.888  -1.187  1.00  0.00           H  
HETATM   24  H12 UNL     1       3.660   1.725  -0.680  1.00  0.00           H  
HETATM   25  H13 UNL     1       4.620   1.147   0.699  1.00  0.00           H  
HETATM   26  H14 UNL     1       3.387   2.477   0.920  1.00  0.00           H  
HETATM   27  H15 UNL     1      -0.355  -3.408  -0.439  1.00  0.00           H  
CONECT    1    2   13   14   15
CONECT    2    3   16   17
CONECT    3    4    5   18
CONECT    4   19   20   21
CONECT    5    6   10   22
CONECT    6    7   23
CONECT    7    8    9    9
CONECT    8   24   25   26
CONECT   10   11   11   12
CONECT   12   27
END

Synonyms

Value	Source
N-Acetyl-L-isoleucine	HMDB
N-Acetylisoleucine	HMDB

Molecular Formula

C₈H₁₅NO₃

Average Mass

173.212

Monoisotopic Mass

173.105193347

IUPAC Name

(2S,3S)-2-acetamido-3-methylpentanoic acid

Traditional Name

(2S,3S)-2-acetamido-3-methylpentanoic acid

CAS Registry Number

Not Available

SMILES

CC[C@H](C)[C@H](NC(C)=O)C(O)=O

InChI Identifier

InChI=1S/C8H15NO3/c1-4-5(2)7(8(11)12)9-6(3)10/h5,7H,4H2,1-3H3,(H,9,10)(H,11,12)/t5-,7-/m0/s1

InChI Key

JDTWZSUNGHMMJM-FSPLSTOPSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as isoleucine and derivatives. Isoleucine and derivatives are compounds containing isoleucine or a derivative thereof resulting from reaction of isoleucine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Isoleucine and derivatives

Alternative Parents

Substituents

Isoleucine or derivatives
N-acyl-alpha-amino acid
N-acyl-alpha amino acid or derivatives
N-acyl-l-alpha-amino acid
Branched fatty acid
Methyl-branched fatty acid
Fatty acyl
Fatty acid
Acetamide
Carboxamide group
Secondary carboxylic acid amide
Carboxylic acid
Monocarboxylic acid or derivatives
Organonitrogen compound
Organic oxide
Organopnictogen compound
Organic nitrogen compound
Organic oxygen compound
Carbonyl group
Organooxygen compound
Hydrocarbon derivative
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

L-isoleucine derivative (CHEBI:21555 )
N-acetyl-L-amino acid (CHEBI:21555 )
N-acetylisoleucine (CHEBI:21555 )

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Property	Value	Source
Water Solubility	25.2 g/L	ALOGPS
logP	0.77	ALOGPS
logP	0.57	ChemAxon
logS	-0.84	ALOGPS
pKa (Strongest Acidic)	4.2	ChemAxon
pKa (Strongest Basic)	-1.6	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	66.4 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	43.54 m³·mol⁻¹	ChemAxon
Polarizability	18.24 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-0900000000-609e437cf2ac060af44f	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-3900000000-9b51475a5da15f8eaf25	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-c26bfff8c0984b37883d	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-2900000000-d5828facfca52464b957	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-08gi-7900000000-c80b9454ed64aa64141c	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-5bfdf3e204a666e2e1c9	2021-09-23	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-24	View Spectrum

Biological Properties

Cellular Locations

Not Available

Biospecimen Locations

Feces

Tissue Locations

Not Available

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference
MMDBr0006082	L-Isoleucine	N-Acetylisoleucine	Not Available		VMH	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria	Firmicutes	4	Human ; Human feces; Human stool	Indirect association between microbiota composition and metabolites measured in host biospecimen
Bacteria	Actinobacteria	1	Human ; Human feces; Human sputum; Human saliva; Human supragingival plaque; Human subgingival plaque	Indirect association between microbiota composition and metabolites measured in host biospecimen

Exposure Sources

Host Biospecimen and Location

Host and Biospecimen	Status	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified				HMDB
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	25037050
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	29808030

External Links

HMDB ID

HMDB0061684

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

7036275

PDB ID

Not Available

ChEBI ID

21555

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

Jellum E, Horn L, Thoresen O, Kvittingen EA, Stokke O: Urinary excretion of N-acetyl amino acids in patients with some inborn errors of amino acid metabolism. Scand J Clin Lab Invest Suppl. 1986;184:21-6. [PubMed:3473611 ]
Sass JO, Mohr V, Olbrich H, Engelke U, Horvath J, Fliegauf M, Loges NT, Schweitzer-Krantz S, Moebus R, Weiler P, Kispert A, Superti-Furga A, Wevers RA, Omran H: Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet. 2006 Mar;78(3):401-9. doi: 10.1086/500563. Epub 2006 Jan 18. [PubMed:16465618 ]
Vanholder R, Baurmeister U, Brunet P, Cohen G, Glorieux G, Jankowski J: A bench to bedside view of uremic toxins. J Am Soc Nephrol. 2008 May;19(5):863-70. doi: 10.1681/ASN.2007121377. Epub 2008 Feb 20. [PubMed:18287557 ]
Toyohara T, Akiyama Y, Suzuki T, Takeuchi Y, Mishima E, Tanemoto M, Momose A, Toki N, Sato H, Nakayama M, Hozawa A, Tsuji I, Ito S, Soga T, Abe T: Metabolomic profiling of uremic solutes in CKD patients. Hypertens Res. 2010 Sep;33(9):944-52. doi: 10.1038/hr.2010.113. Epub 2010 Jul 8. [PubMed:20613759 ]
Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T: NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation. PLoS Genet. 2011 Jul;7(7):e1002169. doi: 10.1371/journal.pgen.1002169. Epub 2011 Jul 7. [PubMed:21750686 ]
Tanaka H, Sirich TL, Plummer NS, Weaver DS, Meyer TW: An Enlarged Profile of Uremic Solutes. PLoS One. 2015 Aug 28;10(8):e0135657. doi: 10.1371/journal.pone.0135657. eCollection 2015. [PubMed:26317986 ]
Ree R, Varland S, Arnesen T: Spotlight on protein N-terminal acetylation. Exp Mol Med. 2018 Jul 27;50(7):1-13. doi: 10.1038/s12276-018-0116-z. [PubMed:30054468 ]

Showing metabocard for N-Acetylisoleucine (MMDBc0000678)

MOL for #<Metabolite:0x00007fdb50b2ebd8>

3D MOL for #<Metabolite:0x00007fdb50b2ebd8>

3D SDF for #<Metabolite:0x00007fdb50b2ebd8>

3D-SDF for #<Metabolite:0x00007fdb50b2ebd8>

PDB for #<Metabolite:0x00007fdb50b2ebd8>

3D PDB for #<Metabolite:0x00007fdb50b2ebd8>

SMILES for #<Metabolite:0x00007fdb50b2ebd8>

INCHI for #<Metabolite:0x00007fdb50b2ebd8>

Structure for #<Metabolite:0x00007fdb50b2ebd8>

3D Structure for #<Metabolite:0x00007fdb50b2ebd8>