T3DB: L-Isoleucine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2014-08-29 06:35:06 UTC

Update Date

2014-12-24 20:26:47 UTC

Accession Number

T3D4364

Identification

Common Name

L-Isoleucine

Class

Small Molecule

Description

L-Isoleucine is one of the essential amino acids that cannot be made by the body and is known for its ability to help endurance and assist in the repair and rebuilding of muscle. This amino acid is important to body builders as it helps boost energy and helps the body recover from training. L-Isoleucine is also classified as a branched-chain amino acid (BCAA). It helps promote muscle recovery after exercise. Isoleucine is actually broken down for energy within the muscle tissue. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.

Compound Type

Amine
Amino Acid, Essential
Animal Toxin
Dietary Supplement
Drug
Food Toxin
Household Toxin
Metabolite
Micronutrient
Natural Compound
Nutraceutical
Organic Compound
Supplement

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Synonym
(2S,3S)-2-amino-3-methyl-Pentanoate
(2S,3S)-2-amino-3-methyl-Pentanoic acid
(2S,3S)-2-Amino-3-methylpentanoate
(2S,3S)-2-Amino-3-methylpentanoic acid
(2S,3S)-a-Amino-b-methyl-N-valerate
(2S,3S)-a-Amino-b-methyl-N-valeric acid
(2S,3S)-a-Amino-b-methylvalerate
(2S,3S)-a-Amino-b-methylvaleric acid
(2S,3S)-alph-Amino-beta-methylvalerate
(2S,3S)-alph-Amino-beta-methylvaleric acid
(2S,3S)-alpha-Amino-beta-merthyl-N-valerate
(2S,3S)-alpha-Amino-beta-merthyl-N-valeric acid
(2S,3S)-alpha-Amino-beta-merthylvalerate
(2S,3S)-alpha-Amino-beta-merthylvaleric acid
(2S,3S)-alpha-Amino-beta-methyl-N-valerate
(2S,3S)-alpha-Amino-beta-methyl-N-valeric acid
(2S,3S)-alpha-Amino-beta-methylvalerate
(2S,3S)-alpha-Amino-beta-methylvaleric acid
(S)-Isoleucine
(S,S)-Isoleucine
2-Amino-3-methylpentanoate
2-Amino-3-methylpentanoic acid
2-Amino-3-methylvalerate
2-Amino-3-methylvaleric acid
2S,3S-Isoleucine
alpha-amino-beta-methylvaleric acid
Erythro-L-Isoleucine
I
Ile
Iso-leucine
Isoleucine
L-(+)-Isoleucine
L-Ile
[S-(R,R)]-2-Amino-3-methylpentanoate
[S-(R,R)]-2-Amino-3-methylpentanoic acid
α-amino-β-methylvaleric acid

Chemical Formula

C₆H₁₃NO₂

Average Molecular Mass

131.173 g/mol

Monoisotopic Mass

131.095 g/mol

CAS Registry Number

73-32-5

IUPAC Name

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

Traditional Name

L-isoleucine

SMILES

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

InChI Identifier

InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1

InChI Key

InChIKey=AGPKZVBTJJNPAG-WHFBIAKZSA-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
Alpha-amino acid
L-alpha-amino acid
Branched fatty acid
Methyl-branched fatty acid
Fatty acid
Fatty acyl
Amino acid
Monocarboxylic acid or derivatives
Carboxylic acid
Organic oxide
Organopnictogen compound
Primary amine
Organooxygen compound
Organonitrogen compound
Primary aliphatic amine
Carbonyl group
Organic oxygen compound
Amine
Organic nitrogen compound
Hydrocarbon derivative
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

aspartate family amino acid (CHEBI:17191 )
proteinogenic amino acid (CHEBI:17191 )
L-alpha-amino acid (CHEBI:17191 )
isoleucine (CHEBI:17191 )
Common amino acids (C00407 )
Amino fatty acids (LMFA01100047 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

All Tissues
Prostate

Pathways

Name	SMPDB Link	KEGG Link
Transcription/Translation	SMP00019	Not Available
Valine, Leucine and Isoleucine Degradation	SMP00032	map00280
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	285.5 dec°C
Boiling Point	Not Available
Solubility	3.44E+004 mg/L (at 25°C)
LogP	-1.7

Predicted Properties

Property	Value	Source
Water Solubility	114 g/L	ALOGPS
logP	-1.7	ALOGPS
logP	-1.5	ChemAxon
logS	-0.06	ALOGPS
pKa (Strongest Acidic)	2.79	ChemAxon
pKa (Strongest Basic)	9.59	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	63.32 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	34.09 m³·mol⁻¹	ChemAxon
Polarizability	14.11 Å³	ChemAxon
Number of Rings	0	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)	splash10-0a4i-0930000000-e78f845bb2a8d4736476	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)	splash10-0a4i-0910000000-de9162d149073d0e2a37	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)	splash10-0a4i-0920000000-599e61f8ccdb6525c7a9	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-0a4i-0910000000-742e44c426c0d6c2a9ac	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)	splash10-05fr-8910000000-dbb33e0f02ac2ca5fedd	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4i-0920000000-37690f426455ac41e2c2	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0930000000-e78f845bb2a8d4736476	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0910000000-de9162d149073d0e2a37	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0920000000-599e61f8ccdb6525c7a9	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0910000000-742e44c426c0d6c2a9ac	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-QQ (Non-derivatized)	splash10-0udi-2392000000-74cca1eb265b8e3d7f43	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-05fr-8910000000-dbb33e0f02ac2ca5fedd	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-9100000000-27891dff695c5db53796	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0910000000-43ec1890f6dbd6aea657	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00b9-9100000000-40bc9ef43da5f18be883	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-000i-9200000000-ae8694c0f3e4dcc608f9	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 (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)	splash10-000i-9300000000-8a23b3e62231eb65f80f	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-00ko-9000000000-ac7e71578d7e1d0e8ce9	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-052f-9000000000-2586d4a089921dd977ed	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-001i-0900000000-5b11521ff6a631376d2b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-3c352f229e4067fcd489	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-8a7ef48fc0c1b6f845c2	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0002-0920000000-2e11aa1c7a5defc386db	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-001i-0900000000-b63ac9cf06eda4c54a81	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-e5b0c8c6b09f541d6dbf	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-d89d16d5c2242e44ec63	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-9000000000-5de583142c7bdb381c8f	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-001i-0900000000-8c75bde35c4a4073ee65	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-001i-0900000000-233a9862f616afea2d17	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-001i-1900000000-375f35065b82b13e6d6e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-00dl-9000000000-d0d4a9f90fe2aca74483	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-0006-9000000000-0018f47571feaf232ff8	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-001r-7900000000-278dc67396114be331ba	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-000i-9000000000-e26c042aa6231eeca071	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-014r-9000000000-b6c1752fd3fbccb3d1c5	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-05mo-9000000000-0569c3162621252ed0a8	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-052f-9000000000-3d52b5d56d3fab45276e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - CE-ESI-TOF (CE-system connected to 6210 Time-of-Flight MS, Agilent) , Positive	splash10-001i-0900000000-720554d58264a9cfdb67	2012-08-31	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0019-9500000000-00268b2694cde281641b	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000i-9000000000-4014793e17e0290790a4	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-eb9a97a14461e524e76e	2016-09-12	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-004r-9000000000-34d4d4cb7042da231eb4	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, 22.5 MHz, D₂O, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, H₂O, experimental)	Not Available	2021-10-10	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

Absorbed from the small intestine by a sodium-dependent active-transport process

Mechanism of Toxicity

(Applies to Valine, Leucine and Isoleucine)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Metabolism

Hepatic

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

The branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Symptoms of hypoglycemia

Treatment

Not Available

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

17191

BioCyc ID

ILE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

ILE

ACToR ID

Not Available

Wikipedia Link

Ile

References

Synthesis Reference

Nelli I. Zhdanova, Tatyana V. Leonova, Ljudmila F. Kozyreva, “Method of producing L-isoleucine using Brevibacterium flavum.” U.S. Patent US4237228, issued February, 1962.

MSDS

Link

General References

Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. [15911239 ]
Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. [12297216 ]
He XY, Yang SY: Roles of type 10 17beta-hydroxysteroid dehydrogenase in intracrinology and metabolism of isoleucine and fatty acids. Endocr Metab Immune Disord Drug Targets. 2006 Mar;6(1):95-102. [16611167 ]
Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24. [14992292 ]
Vaalasti A, Suomalainen H, Kuokkanen K, Rechardt L: Neuropeptides in cutaneous neurofibromas of von Recklinghausen's disease. J Cutan Pathol. 1990 Dec;17(6):371-3. [1981573 ]
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Jalan R, Olde Damink SW, Lui HF, Glabus M, Deutz NE, Hayes PC, Ebmeier K: Oral amino acid load mimicking hemoglobin results in reduced regional cerebral perfusion and deterioration in memory tests in patients with cirrhosis of the liver. Metab Brain Dis. 2003 Mar;18(1):37-49. [12603081 ]
Hervieu G, Segretain D, Nahon JL: Developmental and stage-dependent expression of melanin-concentrating hormone in mammalian germ cells. Biol Reprod. 1996 Jun;54(6):1161-72. [8724342 ]
Suk FM, Lin MH, Newman M, Pan S, Chen SH, Liu JD, Shih C: Replication advantage and host factor-independent phenotypes attributable to a common naturally occurring capsid mutation (I97L) in human hepatitis B virus. J Virol. 2002 Dec;76(23):12069-77. [12414948 ]
Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. [12097436 ]
De Miranda J, Panizzutti R, Foltyn VN, Wolosker H: Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14542-7. Epub 2002 Oct 22. [12393813 ]
Nicholson JK, O'Flynn MP, Sadler PJ, Macleod AF, Juul SM, Sonksen PH: Proton-nuclear-magnetic-resonance studies of serum, plasma and urine from fasting normal and diabetic subjects. Biochem J. 1984 Jan 15;217(2):365-75. [6696735 ]
Blomstrand E, Eliasson J, Karlsson HK, Kohnke R: Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr. 2006 Jan;136(1 Suppl):269S-73S. [16365096 ]
Engelborghs S, Marescau B, De Deyn PP: Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochem Res. 2003 Aug;28(8):1145-50. [12834252 ]
Sato T, Shimada Y, Nagasawa N, Nakanishi S, Jingami H: Amino acid mutagenesis of the ligand binding site and the dimer interface of the metabotropic glutamate receptor 1. Identification of crucial residues for setting the activated state. J Biol Chem. 2003 Feb 7;278(6):4314-21. Epub 2002 Nov 19. [12444084 ]
Edvinsson L: Innervation and effects of dilatory neuropeptides on cerebral vessels. New aspects. Blood Vessels. 1991;28(1-3):35-45. [2001478 ]
Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA: Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem. 1984 Mar;42(3):833-7. [6198473 ]
Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Branched-chain-amino-acid aminotransferase, cytosolic

General Function:: L-valine transaminase activity
Specific Function:: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.
Gene Name:: BCAT1
Uniprot ID:: P54687
Molecular Weight:: 42965.815 Da

References

Goto M, Miyahara I, Hayashi H, Kagamiyama H, Hirotsu K: Crystal structures of branched-chain amino acid aminotransferase complexed with glutamate and glutarate: true reaction intermediate and double substrate recognition of the enzyme. Biochemistry. 2003 Apr 8;42(13):3725-33. [12667063 ]
Chen CD, Huang TF, Lin CH, Guan HH, Hsieh YC, Lin YH, Huang YC, Liu MY, Chang WC, Chen CJ: Purification, crystallization and preliminary X-ray crystallographic analysis of branched-chain aminotransferase from Deinococcus radiodurans. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt 6):492-4. Epub 2007 May 5. [17554170 ]
Beck HC: Branched-chain fatty acid biosynthesis in a branched-chain amino acid aminotransferase mutant of Staphylococcus carnosus. FEMS Microbiol Lett. 2005 Feb 1;243(1):37-44. [15667998 ]
Thage BV, Rattray FP, Laustsen MW, Ardo Y, Barkholt V, Houlberg U: Purification and characterization of a branched-chain amino acid aminotransferase from Lactobacillus paracasei subsp. paracasei CHCC 2115. J Appl Microbiol. 2004;96(3):593-602. [14962140 ]
Madsen SM, Beck HC, Ravn P, Vrang A, Hansen AM, Israelsen H: Cloning and inactivation of a branched-chain-amino-acid aminotransferase gene from Staphylococcus carnosus and characterization of the enzyme. Appl Environ Microbiol. 2002 Aug;68(8):4007-14. [12147502 ]

Target Details

2. Isoleucine--tRNA ligase, cytoplasmic

General Function:: Isoleucine-trna ligase activity
Specific Function:: Not Available
Gene Name:: IARS
Uniprot ID:: P41252
Molecular Weight:: 144496.915 Da

References

Crasto CF, Forrest AK, Karoli T, March DR, Mensah L, O'Hanlon PJ, Nairn MR, Oldham MD, Yue W, Banwell MG, Easton CJ: Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207. Bioorg Med Chem. 2003 Jul 3;11(13):2687-94. [12788342 ]
Wang P, Tang Y, Tirrell DA: Incorporation of trifluoroisoleucine into proteins in vivo. J Am Chem Soc. 2003 Jun 11;125(23):6900-6. [12783542 ]
Mock ML, Michon T, van Hest JC, Tirrell DA: Stereoselective incorporation of an unsaturated isoleucine analogue into a protein expressed in E. coli. Chembiochem. 2006 Jan;7(1):83-7. [16397872 ]
Fukunaga R, Fukai S, Ishitani R, Nureki O, Yokoyama S: Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine. J Biol Chem. 2004 Feb 27;279(9):8396-402. Epub 2003 Dec 12. [14672940 ]
Pezo V, Metzgar D, Hendrickson TL, Waas WF, Hazebrouck S, Doring V, Marliere P, Schimmel P, De Crecy-Lagard V: Artificially ambiguous genetic code confers growth yield advantage. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8593-7. Epub 2004 May 26. [15163798 ]

Target Details

3. Isoleucine--tRNA ligase, mitochondrial

General Function:: Isoleucine-trna ligase activity
Specific Function:: Not Available
Gene Name:: IARS2
Uniprot ID:: Q9NSE4
Molecular Weight:: 113790.565 Da

References

Wang P, Tang Y, Tirrell DA: Incorporation of trifluoroisoleucine into proteins in vivo. J Am Chem Soc. 2003 Jun 11;125(23):6900-6. [12783542 ]
Fukunaga R, Fukai S, Ishitani R, Nureki O, Yokoyama S: Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine. J Biol Chem. 2004 Feb 27;279(9):8396-402. Epub 2003 Dec 12. [14672940 ]
Zhu B, Zhao MW, Eriani G, Wang ED: A present-day aminoacyl-tRNA synthetase with ancestral editing properties. RNA. 2007 Jan;13(1):15-21. Epub 2006 Nov 9. [17095543 ]
Fukunaga R, Yokoyama S: Crystal structure of leucyl-tRNA synthetase from the archaeon Pyrococcus horikoshii reveals a novel editing domain orientation. J Mol Biol. 2005 Feb 11;346(1):57-71. Epub 2004 Dec 19. [15663927 ]
Fukunaga R, Yokoyama S: Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase. J Mol Biol. 2006 Jun 16;359(4):901-12. Epub 2006 Apr 25. [16697013 ]

Target Details

4. Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial

General Function:: Oxidoreductase activity, acting on the ch-ch group of donors, with a flavin as acceptor
Specific Function:: Has greatest activity toward short branched chain acyl-CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl-CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent.
Gene Name:: ACADSB
Uniprot ID:: P45954
Molecular Weight:: 47485.035 Da

References

Korman SH, Andresen BS, Zeharia A, Gutman A, Boneh A, Pitt JJ: 2-ethylhydracrylic aciduria in short/branched-chain acyl-CoA dehydrogenase deficiency: application to diagnosis and implications for the R-pathway of isoleucine oxidation. Clin Chem. 2005 Mar;51(3):610-7. Epub 2004 Dec 22. [15615815 ]
Madsen PP, Kibaek M, Roca X, Sachidanandam R, Krainer AR, Christensen E, Steiner RD, Gibson KM, Corydon TJ, Knudsen I, Wanders RJ, Ruiter JP, Gregersen N, Andresen BS: Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping. Hum Genet. 2006 Feb;118(6):680-90. Epub 2005 Nov 30. [16317551 ]
Korman SH: Inborn errors of isoleucine degradation: a review. Mol Genet Metab. 2006 Dec;89(4):289-99. Epub 2006 Sep 6. [16950638 ]

Target Details

5. Branched-chain-amino-acid aminotransferase, mitochondrial

General Function:: L-valine transaminase activity
Specific Function:: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
Gene Name:: BCAT2
Uniprot ID:: O15382
Molecular Weight:: 44287.445 Da

References

Berger BJ, English S, Chan G, Knodel MH: Methionine regeneration and aminotransferases in Bacillus subtilis, Bacillus cereus, and Bacillus anthracis. J Bacteriol. 2003 Apr;185(8):2418-31. [12670965 ]

Target Details

6. Proton-coupled amino acid transporter 1

General Function:: L-proline transmembrane transporter activity
Specific Function:: Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid (By similarity).
Gene Name:: SLC36A1
Uniprot ID:: Q7Z2H8
Molecular Weight:: 53075.045 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	37000 uM	Not Available	BindingDB 18140

References

Thondorf I, Voigt V, Schafer S, Gebauer S, Zebisch K, Laug L, Brandsch M: Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1). Bioorg Med Chem. 2011 Nov 1;19(21):6409-18. doi: 10.1016/j.bmc.2011.08.058. Epub 2011 Sep 5. [21955456 ]

L-Isoleucine (T3D4364)

Structure for T3D4364: L-Isoleucine

Targets

References

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Binding/Activity Constants

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