General Information of MET (ID: META00191)
Name Lysine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(+)-S-Lysine; (S)-2,6-Diamino-hexanoate; (S)-2,6-Diamino-hexanoic acid; (S)-2,6-Diaminohexanoate; (S)-2,6-Diaminohexanoic acid; (S)-Lysine; (S)-a,e-Diaminocaproate; (S)-a,e-Diaminocaproic acid; (S)-a,epsilon-Diaminocaproate; (S)-a,epsilon-Diaminocaproic acid; (S)-alpha,epsilon-Diaminocaproic acid; 2,6-Diaminohexanoate; 2,6-Diaminohexanoic acid; 6-Amino-L-norleucine; 6-Amino-aminutrin; 6-Ammonio-L-norleucine; Acetate, lysine; Aminutrin; Enisyl; H-Lys-OH; K; L Lysine; L-(+)-Lysine; L-2,6-Diainohexanoate; L-2,6-Diainohexanoic acid; L-2,6-Diaminocaproate; L-2,6-Diaminocaproic acid; L-Lys; L-Lysin; Lys; Lysina; Lysine; Lysine acetate; Lysine acid; Lysine hydrochloride; Lysinum; a-Lysine; alpha-Lysine
Source Food;Plant;Metabolite;Escherichia Coli Metabolite;Yeast Metabolite;Food;Drug;Toxins/Pollutant;Cosmetic;Food additives;TCM Ingredients;Plant Metabolite; Microbial
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
5962
HMDB ID
HMDB0000182
Formula
C6H14N2O2
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
C00047
DrugBank ID
DB00123
ChEBI ID
18019
FooDB ID
FDB000474
ChemSpider ID
5747
METLIN ID
5200
Physicochemical Properties Molecular Weight 146.19 Topological Polar Surface Area 89.3
XlogP -3 Complexity 106
Heavy Atom Count 10 Rotatable Bond Count 5
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 4
Function
L-lysine is an essential amino acid. Normal requirements for lysine have been found to be about 8 g per day or 12 mg/kg in adults. Children and infants need more, 44 mg/kg per day for an eleven to-twelve-year old, and 97 mg/kg per day for three-to six-month old. Lysine is highly concentrated in muscle compared to most other amino acids. Lysine is high in foods such as wheat germ, cottage cheese and chicken. Of meat products, wild game and pork have the highest concentration of lysine. Fruits and vegetables contain little lysine, except avocados. Normal lysine metabolism is dependent upon many nutrients including niacin, vitamin B6, riboflavin, vitamin C, glutamic acid and iron. Excess arginine antagonizes lysine. Several inborn errors of lysine metabolism are known, such as cystinuria, hyperdibasic aminoaciduria I, lysinuric protein intolerance, propionic acidemia, and tyrosinemia I. Most are marked by mental retardation with occasional diverse symptoms such as absence of secondary sex characteristics, undescended testes, abnormal facial structure, anemia, obesity, enlarged liver and spleen, and eye muscle imbalance. Lysine also may be a useful adjunct in the treatment of osteoporosis. Although high protein diets result in loss of large amounts of calcium in urine, so does lysine deficiency. Lysine may be an adjunct therapy because it reduces calcium losses in urine. Lysine deficiency also may result in immunodeficiency. Requirements for this amino acid are probably increased by stress. Lysine toxicity has not occurred with oral doses in humans. Lysine dosages are presently too small and may fail to reach the concentrations necessary to prove potential therapeutic applications. Lysine metabolites, amino caproic acid and carnitine have already shown their therapeutic potential. Thirty grams daily of amino caproic acid has been used as an initial daily dose in treating blood clotting disorders, indicating that the proper doses of lysine, its precursor, have yet to be used in medicine. Low lysine levels have been found in patients with Parkinson's, hypothyroidism, kidney disease, asthma and depression. The exact significance of these levels is unclear, yet lysine therapy can normalize the level and has been associated with improvement of some patients with these conditions. Abnormally elevated hydroxylysines have been found in virtually all chronic degenerative diseases and coumadin therapy. The levels of this stress marker may be improved by high doses of vitamin C. Lysine is particularly useful in therapy for marasmus (wasting) and herpes simplex. It stops the growth of herpes simplex in culture, and has helped to reduce the number and occurrence of cold sores in clinical studies. Dosing has not been adequately studied, but beneficial clinical effects occur in doses ranging from 100 mg to 4 g a day. Higher doses may also be useful, and toxicity has not been reported in doses as high as 8 g per day. Diets high in lysine and low in arginine can be useful in the prevention and treatment of herpes. Some researchers think herpes simplex virus is involved in many other diseases related to cranial nerves such as migraines, Bell's palsy and Meniere's disease. Herpes blister fluid will produce fatal encephalitis in the rabbit (http://www.dcnutrition.com).
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      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 [1]
                      Introduced Variation Agonist (CL-316,243) of Adrb3
                      Induced Change Lysine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that agonist of ADRB3 leads to the increase of lysine levels compared with control group.
      GPCR secretin (GPCR-2)
            Glucagon receptor (GCGR) 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 [2]
                      Introduced Variation Knockout of Gcgr
                      Induced Change Lysine concentration: increase (FC = 2.9)
                      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 lysine levels compared with control group.
      Hydrolases (EC 3)
            Alpha-N-acetylglucosaminidase (NAGLU) 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 [3]
                      Introduced Variation Knockout of Naglu
                      Induced Change Lysine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lysosomal storage diseases [ICD-11: 5C56]
                      Details It is reported that knockout of Naglu leads to the decrease of lysine levels compared with control group.
            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 [4]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change Lysine 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 lysine levels compared with control group.
      Oxidoreductases (EC 1)
            Glyoxylate reductase/hydroxypyruvate reductase (GRHPR) 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 Mutation (patients: c.454dup (p.Thr152Asnfs*39)) of GRHPR
                      Induced Change Lysine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Carbohydrate metabolism disorders [ICD-11: 5C51]
                      Details It is reported that mutation (patients with c.454dup (p.Thr152Asnfs*39)) of GRHPR leads to the increase of lysine levels compared with control group.
            L-2-hydroxyglutarate dehydrogenase (L2HGDH) 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 Mutation (Nonsense mutations or missense mutations) of L2hgdh
                      Induced Change Lysine 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 lysine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Knockout of L2hgdh
                      Induced Change Lysine concentration: increase (FC = 3.4)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Organic acid disorderss [ICD-11: 5C50]
                      Details It is reported that knockout of L2hgdh leads to the increase of lysine 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 [8]
                      Introduced Variation Overexpression of Foxo1
                      Induced Change Lysine concentration: decrease (FC = 0.50)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Foxo1 leads to the decrease of lysine 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 [9]
                      Introduced Variation Knockdown (siRNA) of MYC
                      Induced Change Lysine 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 lysine 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 [10]
                      Introduced Variation Overexpression of Ppargc1a
                      Induced Change Lysine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Ppargc1a leads to the increase of lysine 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 [11]
                      Introduced Variation Knockout of Mgat5
                      Induced Change Lysine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Mgat5 leads to the increase of lysine levels compared with control group.
References
1 Metabolic changes in adipose tissues in response to 3 -adrenergic receptor activation in mice. J Cell Biochem. 2019 Jan;120(1):821-835.
2 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.
3 Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery. Mol Ther. 2017 Mar 1;25(3):792-802.
4 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.
5 Severe child form of primary hyperoxaluria type 2 - a case report revealing consequence of GRHPR deficiency on metabolism. BMC Med Genet. 2017 May 31;18(1):59.
6 Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Rep. 2020 Oct 20;33(3):108293.
7 A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair. PLoS One. 2015 Mar 12;10(3):e0119540.
8 Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1. FEBS Lett. 2019 Jun;593(12):1303-1312.
9 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.
10 PGC-1-mediated branched-chain amino acid metabolism in the skeletal muscle. PLoS One. 2014 Mar 17;9(3):e91006.
11 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.

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