Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0950)
Drug Name
L-glutamine
Synonyms
Glavamin; Glumin (amino acid); Glutamic acid amide; Glutamine (VAN); H-Gln-OH; L-(+)-Glutamine; L-2-Aminoglutaramic acid; L-2-Aminoglutaramidic acid; Cebrogen; L-Glutamic acid 5-amide; L-Glutamic acid gamma-amide; L-Glutamide; L-Glutamin; L-glutamine; Levoglutamid; Levoglutamida; Levoglutamide; Levoglutamidum; Miglu-P; Polyglutamine; Saforis; Stimulina; glumin; glutamic acid 5-amide; glutamine; (2S)-2-amino-4-carbamoylbutanoic acid; (S)-2,5-Diamino-5-oxopentanoic acid; 2-Aminoglutaramic acid, L-; 2-aminoglutaramic acid; 56-85-9
Indication Sickle-cell anaemia [ICD11: 3A51] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 146.14 Topological Polar Surface Area 106
Heavy Atom Count 10 Rotatable Bond Count 4
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 4
Cross-matching ID
PubChem CID
5961
ChEBI ID
CHEBI:18050
CAS Number
56-85-9
TTD Drug ID
D03BVK
Formula
C5H10N2O3
Canonical SMILES
C(CC(=O)N)C(C(=O)O)N
InChI
1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1
InChIKey
ZDXPYRJPNDTMRX-VKHMYHEASA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Amino sugars DM000338 N. A. Unclear 1 [2]
Dihydropteroate DM000333
135398662
Unclear 1 [4] , [5] , [6]
GlcN-6-P DM000335
439217
Oxidation - Deamination 1 [2]
Glutamate DM000317
33032
Unclear 1 [13] , [19] , [24]
Purines DM000336 N. A. Unclear 1 [2]
Pyrimidines DM000337 N. A. Unclear 1 [2]
#NAME? DM000332
119
Oxidation - Decarboxylation 2 [7] , [25]
7,8-dihydrofolate (H2folate) DM000334
135398604
Unclear 2 [4]
Alpha-ketoglutarate DM000323
164533
Hydrolysis - Hydrolyzation 2 [26] , [25] , [27]
Delta-1-pyrroline-5-carboxylic acid DM000318
1196
Unclear 2 [2]
Aspartate DM000324
5960
Unclear 3 [2]
Citrate DM000329
31348
Unclear 3 [2]
L-citrulline DM000319
9750
Unclear 3 [2]
L-Proline DM000322
145742
Unclear 3 [2]
Malate DM003098
525
Unclear 3 [2]
Mammalian target of rapamycin DM000327 N. A. Unclear 3 [2]
Ornithine DM000321
6262
Unclear 3 [2]
AN-9 M3 DM000330
264
Unclear 4 [2]
Asparagine DM000326
6267
Unclear 4 [2]
Collagen DM000328 N. A. Unclear 4 [2]
Fatty acids DM000330 N. A. Unclear 4 [2]
L-arginine DM003102
6322
Unclear 4 [2]
Nucleotides DM000325 N. A. Unclear 4 [2]
PYR DM000331
107735
Unclear 4 [2]
NO DM000320
145068
Unclear 5 [2]
⏷ Show the Full List of 25  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001537 L-glutamine L-glutamate Unclear GLUL ... [13], [19], [24]
MR001538 L-glutamine Dihydropteroate Unclear fpgS [4], [5], [6]
MR001539 L-glutamine Glucosamine-6-phosphate Oxidation - Deamination GFPT1 [2]
MR001540 L-glutamine Purines Unclear Unclear [2]
MR001541 L-glutamine Pyrimidines Unclear Unclear [2]
MR001542 L-glutamine Amino sugars Unclear Unclear [2]
MR001536 Dihydropteroate Dihydrofolate Unclear Unclear [4]
MR001521 L-glutamate 1-pyrroline-5-carboxylic acid Unclear Unclear [2]
MR001522 L-glutamate Alpha-ketoglutarate Hydrolysis - Hydrolyzation Unclear [26], [25], [27]
MR001523 L-glutamate GABA Oxidation - Decarboxylation gadA ... [7], [25]
MR001524 1-pyrroline-5-carboxylic acid L-citrulline Unclear Unclear [2]
MR001525 1-pyrroline-5-carboxylic acid L-Ornithine Unclear Unclear [2]
MR001526 1-pyrroline-5-carboxylic acid L-Proline Unclear Unclear [2]
MR001528 Alpha-ketoglutarate Aspartate Unclear Unclear [2]
MR001529 Alpha-ketoglutarate Mammalian target of rapamycin Unclear Unclear [2]
MR001530 Alpha-ketoglutarate Citrate Unclear Unclear [2]
MR001531 Alpha-ketoglutarate Malate Unclear Unclear [2]
MR001532 Aspartate Nucleotides Unclear Unclear [2]
MR001533 Aspartate Asparagine Unclear ASNS [2]
MR001535 Citrate Fatty acids Unclear Unclear [2]
MR001527 L-citrulline L-arginine Unclear ASS1 ... [2]
MR001544 Malate Pyruvate Unclear ME1 [2]
MR001534 Mammalian target of rapamycin Collagen Unclear Unclear [2]
MR001543 L-arginine NO Unclear Unclear [2]
⏷ Show the Full List of 24 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Argininosuccinate lyase (ASL) DMEN011 Homo sapiens
ARLY_HUMAN
1.1.5.5
[2]
Argininosuccinate synthase (ASS1) DMEN010 Homo sapiens
ASSY_HUMAN
Not Available [2]
Asparagine synthetase (ASNS) DME0154 Homo sapiens
ASNS_HUMAN
6.3.5.4
[3]
Folylpolyglutamate synthetase (fpgS) DME1239 Lactobacillus casei
FPGS_LACCA
6.3.2.17
[4]
Glutamate decarboxylase (gadB) DME2101 Lactobacillus brevis
A0A0B5GI57_LACBR
4.1.1.15
[5] , [6]
Glutamate decarboxylase (gadB) DME1305 Shigella flexneri
DCEA_SHIFL
4.1.1.15
[7]
Glutamate decarboxylase (gadB) DME1344 Bifidobacterium adolescentis
A0A174BCD4_BIFAD
4.1.1.15
[6]
Glutamate decarboxylase (gadB) DME1118 Lactobacillus johnsonii
A9ZM78_LACBR
4.1.1.15
[5]
Glutamate decarboxylase (gadB) DME1303 Listeria monocytogenes
DCEB_LISMO
4.1.1.15
[7]
Glutamate decarboxylase (gadB) DME1304 Escherichia coli
DCEB_ECOLI
4.1.1.15
[7]
Glutamate decarboxylase (gadB) DME1306 Lactococcus lactis
DCE_LACLA
4.1.1.15
[7]
Glutamate decarboxylase (gadB) DME1307 Bifidobacterium dentium
D2Q5X3_BIFDB
4.1.1.15
[6]
Glutamate decarboxylase (gadB) DME1339 Lactobacillus plantarum
A0A1E3KVW8_LACPN
4.1.1.15
[6]
Glutamate decarboxylase (gadB) DME1346 Bifidobacterium angulatum
A0A126SV18_9BIFI
4.1.1.15
[6]
Glutamate racemase (MurI) DME1120 Aquifex pyrophilus
MURI_AQUPY
5.1.1.3
[8]
Glutamate racemase (MurI) DME1121 Escherichia coli
MURI_ECOLI
5.1.1.3
[8]
Glutamate racemase (MurI) DME1123 Lactobacillus fermentum
MURI_LACFE
5.1.1.3
[8]
Glutamate racemase (MurI) DME1953 Streptococcus mutans
MURI_STRMU
5.1.1.3
[9]
Glutamate racemase (MurI) DME1124 Bacillus subtilis
MURI1_BACSU
5.1.1.3
[8]
Glutamate racemase (MurI) DME1126 Bacillus anthracis
Q81UL8_BACAN
5.1.1.3
[8]
Glutamate racemase (MurI) DME1125 Bacillus pumilus
MURI2_BACSU
5.1.1.3
[8]
Glutamate-cysteine ligase catalytic (GCLC) DME0485 Homo sapiens
GSH1_HUMAN
6.3.2.2
[10]
Glutamate-cysteine ligase regulatory (GCLM) DME0486 Homo sapiens
GSH0_HUMAN
6.3.2.2
[11]
Glutamine amidotransferase (GMPS) DME0159 Homo sapiens
GUAA_HUMAN
6.3.5.2
[12]
Glutamine synthetase (GLUL) DME0418 Homo sapiens
GLNA_HUMAN
6.3.1.2
[13]
Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 (GFPT1) DMEN014 Homo sapiens
GFPT1_HUMAN
Not Available [2]
Glutamine-dependent NAD(+) synthetase (NADSYN1) DME0155 Homo sapiens
NADE_HUMAN
6.3.5.1
[14]
Glutaminyl-tRNA synthetase (GLNRS) DME0157 Homo sapiens
SYQ_HUMAN
6.1.1.18
[15]
Glutamyl-tRNA(Gln) amidotransferase B (GATB) DME0158 Homo sapiens
GATB_HUMAN
6.3.5.7
[16]
Hexosephosphate aminotransferase 2 (GFPT2) DME0156 Homo sapiens
GFPT2_HUMAN
2.6.1.16
[16]
Kynurenine aminotransferase I (KYAT1) DME0160 Homo sapiens
KAT1_HUMAN
2.6.1.7
[17]
L-glutamine amidohydrolase (GLS) DME0126 Homo sapiens
GLSK_HUMAN
3.5.1.2
[18]
L-glutamine amidohydrolase (GLS) DME0126 Homo sapiens
GLSK_HUMAN
3.5.1.2
[19]
N-acetylglutamate synthase (NAGS) DME0534 Homo sapiens
NAGS_HUMAN
2.3.1.1
[20]
NADP-dependent malic enzyme (ME1) DME0504 Homo sapiens
MAOX_HUMAN
1.1.1.40
[2]
Phosphoribosylformylglycinamidine synthase (PFAS) DME0161 Homo sapiens
PUR4_HUMAN
6.3.5.3
[16]
Transglutaminase E (TGM3) DME0165 Homo sapiens
TGM3_HUMAN
2.3.2.13
[16]
Transglutaminase H (TGM2) DME0162 Homo sapiens
TGM2_HUMAN
2.3.2.13
[21]
Transglutaminase K (TGM1) DME0166 Homo sapiens
TGM1_HUMAN
2.3.2.13
[22]
Transglutaminase X (TGM5) DME0163 Homo sapiens
TGM5_HUMAN
2.3.2.13
[16]
Transglutaminase Y (TGM6) DME0164 Homo sapiens
TGM3L_HUMAN
2.3.2.13
[16]
Transglutaminase Z (TGM7) DME0167 Homo sapiens
TGM7_HUMAN
2.3.2.13
[16]
⏷ Show the Full List of 42  DME(s)
Experimental Enzyme Kinetic Data of This Drug
DME Name DME Info Kinetic Data Uniprot ID REF
Glutamate-cysteine ligase catalytic (GCLC) DME0485 Km = 1.9 microM
GSH1_HUMAN
[11]
Glutamate-cysteine ligase regulatory (GCLM) DME0486 Km = 1.9 microM
GSH0_HUMAN
[11]
L-glutamine amidohydrolase (GLS) DME0126 Km = 0.4 microM
GLSK_HUMAN
[18]
Glutamate racemase (MurI) DME1120 Km = 3300 microM
MURI_AQUPY
[8]
Glutamate racemase (MurI) DME1121 Km = 4000 microM
MURI_ECOLI
[8]
Glutamate racemase (MurI) DME1123 Km = 330 microM
MURI_LACFE
[8]
Glutamine-dependent NAD(+) synthetase (NADSYN1) DME0155 Km = 1.44 microM
NADE_HUMAN
[23]
N-acetylglutamate synthase (NAGS) DME0534 Km = 2.5 microM
NAGS_HUMAN
[20]
Glutamate racemase (MurI) DME1124 Km = 50000 microM
MURI1_BACSU
[8]
Glutamate racemase (MurI) DME1126 Km = 3700 microM
Q81UL8_BACAN
[8]
Glutamate racemase (MurI) DME1125 Km = 50000 microM
MURI2_BACSU
[8]
⏷ Show the Full List of 11  DME(s)
References
1 L-Glutamine was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 The Emerging Role of l-Glutamine in Cardiovascular Health and Disease Nutrients. 2019 Sep 4;11(9):2092. doi: 10.3390/nu11092092.
3 A convenient gHMQC-based NMR assay for investigating ammonia channeling in glutamine-dependent amidotransferases: studies of Escherichia coli asparagine synthetase B. Biochemistry. 2007 Apr 24;46(16):4840-9.
4 Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site. Biochemistry. 2008 Feb 26;47(8):2388-96.
5 Exploring the contributions of two glutamate decarboxylase isozymes in Lactobacillus brevis to acid resistance and gamma-aminobutyric acid production. Microb Cell Fact. 2018 Nov 19;17(1):180.
6 GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe. 2016 Dec;42:197-204.
7 Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operon. Mol Microbiol. 2012 Nov;86(4):770-86.
8 Structural and functional analysis of two glutamate racemase isozymes from Bacillus anthracis and implications for inhibitor design. J Mol Biol. 2007 Aug 31;371(5):1219-37.
9 Inactivation of glutamate racemase (MurI) eliminates virulence in Streptococcus mutans. Microbiol Res. 2016 May-Jun;186-187:1-8.
10 Kinetic measurement by LC/MS of gamma-glutamylcysteine ligase activity. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):32-8.
11 The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase. Adv Enzymol Relat Areas Mol Biol. 1999;73:209-67, xii.
12 Thermodynamic characterization of the protein-protein interaction in the heteromeric Bacillus subtilis pyridoxalphosphate synthase. Biochemistry. 2007 May 1;46(17):5131-9.
13 Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation Nutrients. 2018 Oct 23;10(11):1564. doi: 10.3390/nu10111564.
14 Glutamine-dependent NAD+ synthetase. How a two-domain, three-substrate enzyme avoids waste. J Biol Chem. 2006 Nov 3;281(44):33395-402.
15 Synthesis of beta-ketophosphonate analogs of glutamyl and glutaminyl adenylate, and selective inhibition of the corresponding bacterial aminoacyl-tRNA synthetases. Bioorg Med Chem. 2007 Jan 1;15(1):295-304.
16 How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
17 Determination of kynurenic acid in human serum and its correlation with the concentration of certain amino acids. Clin Chim Acta. 2007 Feb;377(1-2):174-8.
18 Full-length human glutaminase in complex with an allosteric inhibitor. Biochemistry. 2011 Dec 20;50(50):10764-70.
19 The glutamine-alpha-ketoglutarate (AKG) metabolism and its nutritional implications Amino Acids. 2016 Sep;48(9):2067-80. doi: 10.1007/s00726-016-2254-8.
20 Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. Mol Genet Metab. 2006 Mar;87(3):226-32.
21 Phage display selection of efficient glutamine-donor substrate peptides for transglutaminase 2. Protein Sci. 2006 Nov;15(11):2466-80.
22 A three-dimensional model of the human transglutaminase 1: insights into the understanding of lamellar ichthyosis. J Mol Model. 2007 Jan;13(1):233-46.
23 Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency. J Biol Chem. 2003 Mar 28;278(13):10914-21.
24 Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics - synthesis and properties. J Enzyme Inhib Med Chem. 2022 Dec;37(1):1928-1956. doi: 10.1080/14756366.2022.2096018.
25 The delta subunit of the GABA(A) receptor is necessary for the GPT2-promoted breast cancer metastasis. Theranostics. 2023 Feb 21;13(4):1355-1369. doi: 10.7150/thno.80544.
26 -KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis. Cell Death Discov. 2023 Jun 12;9(1):182. doi: 10.1038/s41420-023-01475-1.
27 The helminth derived peptide FhHDM-1 redirects macrophage metabolism towards glutaminolysis to regulate the pro-inflammatory response. Front Immunol. 2023 Jan 25;14:1018076. doi: 10.3389/fimmu.2023.1018076.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.