Details of Metabolite

General Information of MET (ID: META00185)
Name Threonine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(2S)-Threonine; (2S,3R)-(-)-Threonine; (2S,3R)-2-Amino-3-hydroxybutanoate; (2S,3R)-2-Amino-3-hydroxybutanoic acid; (2S,3R)-2-Amino-3-hydroxybutyrate; (2S,3R)-2-Amino-3-hydroxybutyric acid; (R-(R*,s*))-2-amino-3-hydroxybutanoate; (R-(R*,s*))-2-amino-3-hydroxybutanoic acid; (S)-Threonine; 2-Amino-3-hydroxybutanoate; 2-Amino-3-hydroxybutanoic acid; 2-Amino-3-hydroxybutyrate; 2-Amino-3-hydroxybutyric acid; L Threonine; L-(-)-Threonine; L-2-Amino-3-hydroxybutyrate; L-2-Amino-3-hydroxybutyric acid; L-Threonin; L-a-Amino-b-hydroxybutyrate; L-a-Amino-b-hydroxybutyric acid; L-alpha-Amino-beta-hydroxybutyric acid; T; THREONINE; Thr; Threonin; [R-(R*,s*)]-2-amino-3-hydroxy-butanoate; [R-(R*,s*)]-2-amino-3-hydroxy-butanoic acid; [R-(R*,s*)]-2-amino-3-hydroxybutanoate; [R-(R*,s*)]-2-amino-3-hydroxybutanoic acid
Source Aliphatic acyclic compounds
Structure Type   Amino acids, peptides, and analogues  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic acids and derivatives
Carboxylic acids and derivatives
Amino acids, peptides, and analogues
PubChem CID
6288
HMDB ID
HMDB0000167
Formula
C4H9NO3
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00188
DrugBank ID
DB00156
ChEBI ID
16857
FooDB ID
FDB011999
ChemSpider ID
6051
METLIN ID
32
Physicochemical Properties Molecular Weight 119.12 Topological Polar Surface Area 83.6
XlogP -2.9 Complexity 93.3
Heavy Atom Count 8 Rotatable Bond Count 2
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 4
Function
Threonine is an essential amino acid in humans. It is abundant in human plasma, particularly in newborns. Severe deficiency of threonine causes neurological dysfunction and lameness in experimental animals. Threonine is an immunostimulant which promotes the growth of thymus gland. It also can probably promote cell immune defense function. This amino acid has been useful in the treatment of genetic spasticity disorders and multiple sclerosis at a dose of 1 gram daily. It is highly concentrated in meat products, cottage cheese and wheat germ. (http://www.dcnutrition.com/AminoAcids/) The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. The whey proteins which are used for infant formulas are sweet whey proteins. Sweet whey results from cheese production. Threonine catabolism in mammals appears to be due primarily (70-80%) to the activity of threonine dehydrogenase (EC 1.1.1.103) that oxidizes threonine to 2-amino-3-oxobutyrate, which forms glycine and acetyl CoA, whereas threonine dehydratase (EC 4.2.1.16) that catabolizes threonine into 2-oxobutyrate and ammonia, is significantly less active. Increasing the threonine plasma concentrations leads to accumulation of threonine and glycine in the brain. Such accumulation affects the neurotransmitter balance which may have consequences for the brain development during early postnatal life. Thus, excessive threonine intake during infant feeding should be avoided.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Amino acid/auxin permease (AAAP)
            Solute carrier family 38 member 2 (SLC38A2) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockdown (siRNA) of SLC38A2
                      Induced Change Threonine concentration: increase (FC = 1.80)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockdown of SLC38A2 leads to the increase of threonine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Overexpression of SLC38A2
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC38A2 leads to the increase of threonine levels compared with control group.
            Solute carrier family 38 member 3 (SLC38A3) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockout of Slc38a3
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Slc38a3 leads to the increase of threonine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockout of SLC38A3
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of SLC38A3 leads to the increase of threonine levels compared with control group.
      Amino acid/polyamine transporter (AAPT)
            Asc-type amino transporter 1 (SLC7A10) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Overexpression of SLC7A10
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC7A10 leads to the increase of threonine levels compared with control group.
            Integral membrane E16 (SLC7A5) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Overexperisson of SLC7A5
                      Induced Change Threonine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that co-overexperisson of SLC7A5 and SLC7A8 leads to the decrease of threonine levels compared with control group.
            L-type amino acid transporter 2 (LAT2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Overexperisson of SLC7A8
                      Induced Change Threonine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that co-overexperisson of SLC7A5 and SLC7A8 leads to the decrease of threonine levels compared with control group.
      Dicarboxylate/amino acid:cation symporter (DAACS)
            Neutral amino acid transporter A (SLC1A4) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Knockout of SLC1A4
                      Induced Change Threonine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of SLC1A4 leads to the decrease of threonine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Knockout of SLC1A4
                      Induced Change Threonine concentration: increase (FC = 1.40 - 1.60)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of SLC1A4 leads to the increase of threonine levels compared with control group.
      GPCR rhodopsin (GPCR-1)
            Adrenergic receptor beta-3 (ADRB3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Agonist (CL-316,243) of Adrb3
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that agonist of ADRB3 leads to the increase of threonine levels compared with control group.
      GPCR secretin (GPCR-2)
            Glucagon receptor (GCGR) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Antagonist (GRA1) of GCGR
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hyperglycemic hyperosmolar syndrome [ICD-11: 5A20]
                      Details It is reported that antagonist of GCGR leads to the increase of threonine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [9]
                      Introduced Variation Knockout of Gcgr
                      Induced Change Threonine concentration: increase (FC = 9.6)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Type 2 diabetes mellitus [ICD-11: 5A11]
                      Details It is reported that knockout of GCGR leads to the increase of threonine levels compared with control group.
      Hydrolases (EC 3)
            Leukotriene-C4 hydrolase (GGT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [10]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Renal cell carcinoma [ICD-11: 2C90]
                      Details It is reported that knockdown of GGT1 leads to the increase of threonine levels compared with control group.
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [11]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Threonine concentration: decrease (FC = 0.51 / 0.61)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the decrease of threonine levels compared with control group.
      Oxidoreductases (EC 1)
            L-2-hydroxyglutarate dehydrogenase (L2HGDH) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [12]
                      Introduced Variation Mutation (Nonsense mutations or missense mutations) of L2hgdh
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Melanoma [ICD-11: 2C30]
                      Details It is reported that mutation (nonsense mutations or missense mutations leading to KMT2D loss) of L2hgdh leads to the increase of threonine levels compared with control group.
      Pore-forming PNC peptide (PNC)
            Cellular tumor antigen p53 (TP53) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [13]
                      Introduced Variation Knockout of TP53
                      Induced Change Threonine concentration: decrease (Log2 FC=0.66)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockout of TP53 leads to the decrease of threonine levels compared with control group.
      Transcription factor (TF)
            Forkhead box protein O1 (FOXO1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [14]
                      Introduced Variation Overexpression of Foxo1
                      Induced Change Threonine concentration: decrease (FC = 0.70)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Foxo1 leads to the decrease of threonine levels compared with control group.
            Myc proto-oncogene protein (MYC) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [15]
                      Introduced Variation Knockdown (siRNA) of MYC
                      Induced Change Threonine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockdown of MYC leads to the decrease of threonine levels compared with control group.
      Transcriptional coactivator (TC)
            PPAR-gamma coactivator 1-alpha (PPARGC1A) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [16]
                      Introduced Variation Knockout of Ppargc1a
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Congestive heart failure [ICD-11: BD10]
                      Details It is reported that knockout of Ppargc1a leads to the increase of threonine levels compared with control group.
      Transferases (EC 2)
            Acetylglucosaminyltransferase 5 (MGAT5) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [17]
                      Introduced Variation Knockout of Mgat5
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Mgat5 leads to the increase of threonine levels compared with control group.
            SNF-related serine/threonine-protein kinase (SNRK) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [18]
                      Introduced Variation Knockdown (shRNA) of SNRK
                      Induced Change Threonine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockdown of SNRK leads to the increase of threonine levels compared with control group.
References
1 SNAT2 silencing prevents the osmotic induction of transport system A and hinders cell recovery from hypertonic stress. FEBS Lett. 2005 Jun 20;579(16):3376-80.
2 Primary structure, functional characteristics and tissue expression pattern of human ATA2, a subtype of amino acid transport system A. Biochim Biophys Acta. 2000 Jul 31;1467(1):1-6.
3 Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney. Pflugers Arch. 2016 Feb;468(2):213-27.
4 Cloning and characterization of a human brain Na(+)-independent transporter for small neutral amino acids that transports D-serine with high affinity. Neurosci Lett. 2000 Jun 30;287(3):231-5.
5 Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J Biol Chem. 1999 Jul 9;274(28):19738-44.
6 ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d-serine and neurodevelopment. Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):9628-9633.
7 Metabolic changes in adipose tissues in response to 3 -adrenergic receptor activation in mice. J Cell Biochem. 2019 Jan;120(1):821-835.
8 Anti-diabetic efficacy and impact on amino acid metabolism of GRA1, a novel small-molecule glucagon receptor antagonist. PLoS One. 2012;7(11):e49572.
9 Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes. BMC Genomics. 2011 Jun 1;12:281.
10 Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6274-E6282.
11 Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab. 2014 Nov 4;2:24.
12 Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Rep. 2020 Oct 20;33(3):108293.
13 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.
14 Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1. FEBS Lett. 2019 Jun;593(12):1303-1312.
15 Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7697-E7706.
16 Heart specific PGC-1 deletion identifies metabolome of cardiac restricted metabolic heart failure. Cardiovasc Res. 2019 Jan 1;115(1):107-118.
17 N-glycan remodeling on glucagon receptor is an effector of nutrient sensing by the hexosamine biosynthesis pathway. J Biol Chem. 2014 Jun 6;289(23):15927-41.
18 Sucrose Nonfermenting-Related Kinase Enzyme-Mediated Rho-Associated Kinase Signaling is Responsible for Cardiac Function. Circ Cardiovasc Genet. 2016 Dec;9(6):474-486.

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