L-SERINE

General Information

Mainterm	L-SERINE
Doc Type	ASP
CAS Reg.No.(or other ID)	56-45-1
Regnum	172.320

From www.fda.gov

Computed Descriptors

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2D Structure
CID	5951
IUPAC Name	(2S)-2-amino-3-hydroxypropanoic acid
InChI	InChI=1S/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)/t2-/m0/s1
InChI Key	MTCFGRXMJLQNBG-REOHCLBHSA-N
Canonical SMILES	C(C(C(=O)O)N)O
Molecular Formula	C3H7NO3
Wikipedia	L-Serine

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	105.093
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Complexity	72.6
CACTVS Substructure Key Fingerprint	A A A D c Y B C M A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A H g A Q C A A A C C j h g A Y A C A B A A g A I A A C Q C A A A A A A A A A A A A I G A A A A C E A Q A A A A A Q A A B M A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area	83.6
Monoisotopic Mass	105.043
Exact Mass	105.043
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	7
Defined Atom Stereocenter Count	1
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

Food Additives Biosynthesis/Degradation

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB-	0.6529
Human Intestinal Absorption	HIA+	0.9407
Caco-2 Permeability	Caco2-	0.7839
P-glycoprotein Substrate	Non-substrate	0.7693
P-glycoprotein Inhibitor	Non-inhibitor	0.9862
P-glycoprotein Inhibitor	Non-inhibitor	0.9877
Renal Organic Cation Transporter	Non-inhibitor	0.9436
Distribution
Subcellular localization	Lysosome	0.6959
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8673
CYP450 2D6 Substrate	Non-substrate	0.8460
CYP450 3A4 Substrate	Non-substrate	0.8389
CYP450 1A2 Inhibitor	Non-inhibitor	0.9087
CYP450 2C9 Inhibitor	Non-inhibitor	0.9512
CYP450 2D6 Inhibitor	Non-inhibitor	0.9349
CYP450 2C19 Inhibitor	Non-inhibitor	0.9450
CYP450 3A4 Inhibitor	Non-inhibitor	0.9080
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9914
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9923
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9811
AMES Toxicity	Non AMES toxic	0.9088
Carcinogens	Non-carcinogens	0.8200
Fish Toxicity	Low FHMT	0.8678
Tetrahymena Pyriformis Toxicity	Low TPT	0.9972
Honey Bee Toxicity	Low HBT	0.5782
Biodegradation	Ready biodegradable	0.9489
Acute Oral Toxicity	III	0.5142
Carcinogenicity (Three-class)	Non-required	0.7108

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	0.1752	LogS
Caco-2 Permeability	-0.1022	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	1.2700	LD50, mol/kg
Fish Toxicity	2.8128	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	-1.0558	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	None
Mechanism of Toxicity	L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.
Metabolism	None
Toxicity Values	None
Lethal Dose	None
Carcinogenicity (IARC Classification)	No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level	None
Health Effects	None
Treatment	None
Reference	de Koning TJ, Snell K, Duran M, Berger R, Poll-The BT, Surtees R: L-serine in disease and development. Biochem J. 2003 May 1;371(Pt 3):653-61.[12534373 ] 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 ] 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 ] 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 ] 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 ] 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 ] 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 ] 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 ] Haas W, Grabe K, Geis C, Pach T, Stoll K, Fuchs M, Haberl B, Loy C: Recognition and invasion of human skin by Schistosoma mansoni cercariae: the key-role of L-arginine. Parasitology. 2002 Feb;124(Pt 2):153-67.[11860033 ] Fontaine M, Porchet N, Largilliere C, Marrakchi S, Lhermitte M, Aubert JP, Degand P: Biochemical contribution to diagnosis and study of a new case of D-glyceric acidemia/aciduria. Clin Chem. 1989 Oct;35(10):2148-51.[2551543 ] Furuya S, Watanabe M: Novel neuroglial and glioglial relationships mediated by L-serine metabolism. Arch Histol Cytol. 2003 May;66(2):109-21.[12846552 ] Kaumeyer JF, Polazzi JO, Kotick MP: The mRNA for a proteinase inhibitor related to the HI-30 domain of inter-alpha-trypsin inhibitor also encodes alpha-1-microglobulin (protein HC). Nucleic Acids Res. 1986 Oct 24;14(20):7839-50.[2430261 ] Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindstrom LH, Iyo M: Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jun;29(5):767-9.[15939521 ] Castedo M, Ferri KF, Blanco J, Roumier T, Larochette N, Barretina J, Amendola A, Nardacci R, Metivier D, Este JA, Piacentini M, Kroemer G: Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation. J Exp Med. 2001 Oct 15;194(8):1097-110.[11602639 ] Liu T, Zhu E, Wang L, Okada T, Yamaguchi A, Okada N: Abnormal expression of Rb pathway-related proteins in salivary gland acinic cell carcinoma. Hum Pathol. 2005 Sep;36(9):962-70.[16153458 ] Franchi-Gazzola R, Gazzola GC, Dall'Asta V, Guidotti GG: The transport of alanine, serine, and cysteine in cultured human fibroblasts. J Biol Chem. 1982 Aug 25;257(16):9582-7.[6809740 ] Yamamoto T, Nishizaki I, Nukada T, Kamegaya E, Furuya S, Hirabayashi Y, Ikeda K, Hata H, Kobayashi H, Sora I, Yamamoto H: Functional identification of ASCT1 neutral amino acid transporter as the predominant system for the uptake of L-serine in rat neurons in primary culture. Neurosci Res. 2004 May;49(1):101-11.[15099708 ] Mackie S, Aitken A: Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease. FEBS J. 2005 Aug;272(16):4202-10.[16098201 ] Kobza K, Camporeale G, Rueckert B, Kueh A, Griffin JB, Sarath G, Zempleni J: K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase. FEBS J. 2005 Aug;272(16):4249-59.[16098205 ] Whittemore AS, Cirillo PM, Feldman D, Cohn BA: Prostate specific antigen levels in young adulthood predict prostate cancer risk: results from a cohort of Black and White Americans. J Urol. 2005 Sep;174(3):872-6; discussion 876.[16093978 ] Schulz I, Zeitschel U, Rudolph T, Ruiz-Carrillo D, Rahfeld JU, Gerhartz B, Bigl V, Demuth HU, Rossner S: Subcellular localization suggests novel functions for prolyl endopeptidase in protein secretion. J Neurochem. 2005 Aug;94(4):970-9.[16092940 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Organic acids and derivatives
Class	Carboxylic acids and derivatives
Subclass	Amino acids, peptides, and analogues
Intermediate Tree Nodes	Amino acids and derivatives - Alpha amino acids and derivatives
Direct Parent	Serine and derivatives
Alternative Parents	Beta hydroxy acids and derivatives Organopnictogen compounds Amino acids Monocarboxylic acids and derivatives Carboxylic acids Monoalkylamines L-alpha-amino acids Hydrocarbon derivatives Organic oxides Primary alcohols Carbonyl compounds
Molecular Framework	Aliphatic acyclic compounds
Substituents	Serine or derivatives - Alpha-amino acid - L-alpha-amino acid - Beta-hydroxy acid - Hydroxy acid - Amino acid - Carboxylic acid - Monocarboxylic acid or derivatives - Alcohol - Primary amine - Primary alcohol - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Primary aliphatic amine - Organic oxide - Organopnictogen compound - Carbonyl group - Organic oxygen compound - Amine - Organic nitrogen compound - Aliphatic acyclic compound
Description	This compound belongs to the class of organic compounds known as serine and derivatives. These are compounds containing serine or a derivative thereof resulting from reaction of serine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

From ClassyFire

Targets

Target Details

L-serine dehydratase/L-threonine deaminase

General Function:: Pyridoxal phosphate binding
Gene Name:: SDS
Uniprot ID:: P20132
Molecular Weight:: 34625.105 Da

References

Wong HC, Lessie TG: Hydroxy amino acid metabolism in Pseudomonas cepacia: role of L-serine deaminase in dissimilation of serine, glycine, and threonine. J Bacteriol. 1979 Oct;140(1):240-5. [500557 ]

Target Details

Serine--tRNA ligase, cytoplasmic

General Function:: Serine-trna ligase activity
Specific Function:: Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).
Gene Name:: SARS
Uniprot ID:: P49591
Molecular Weight:: 58776.785 Da

References

McClendon CL, Vaidehi N, Kam VW, Zhang D, Goddard WA 3rd: Fidelity of seryl-tRNA synthetase to binding of natural amino acids from HierDock first principles computations. Protein Eng Des Sel. 2006 May;19(5):195-203. Epub 2006 Mar 3. [16517553 ]

Target Details

Serine--pyruvate aminotransferase

General Function:: Transaminase activity
Gene Name:: AGXT
Uniprot ID:: P21549
Molecular Weight:: 43009.535 Da

References

Son JH, Yoo HH, Kim DH: Activation of de novo synthetic pathway of ceramides is responsible for the initiation of hydrogen peroxide-induced apoptosis in HL-60 cells. J Toxicol Environ Health A. 2007 Aug;70(15-16):1310-8. [17654249 ]

Target Details

Cystathionine beta-synthase

General Function:: Ubiquitin protein ligase binding
Specific Function:: Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (By similarity).
Gene Name:: CBS
Uniprot ID:: P35520
Molecular Weight:: 60586.05 Da

References

Qu K, Lee SW, Bian JS, Low CM, Wong PT: Hydrogen sulfide: neurochemistry and neurobiology. Neurochem Int. 2008 Jan;52(1-2):155-65. Epub 2007 Jun 8. [17629356 ]

Target Details

Serine racemase

General Function:: Threonine racemase activity
Specific Function:: Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine.
Gene Name:: SRR
Uniprot ID:: Q9GZT4
Molecular Weight:: 36565.905 Da

References

Ying-Luan Z, Zhao YL, Mori H: [Role of D-serine in the mammalian brain]. Brain Nerve. 2007 Jul;59(7):725-30. [17663143 ]

Target Details

Serine palmitoyltransferase 1

General Function:: Serine c-palmitoyltransferase activity
Specific Function:: Serine palmitoyltransferase (SPT). The heterodimer formed with SPTLC2 or SPTLC3 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.
Gene Name:: SPTLC1
Uniprot ID:: O15269
Molecular Weight:: 52743.41 Da

References

Yard BA, Carter LG, Johnson KA, Overton IM, Dorward M, Liu H, McMahon SA, Oke M, Puech D, Barton GJ, Naismith JH, Campopiano DJ: The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis. J Mol Biol. 2007 Jul 27;370(5):870-86. Epub 2007 May 10. [17559874 ]

Target Details

Serine palmitoyltransferase 2

General Function:: Serine c-palmitoyltransferase activity
Specific Function:: Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate.
Gene Name:: SPTLC2
Uniprot ID:: O15270
Molecular Weight:: 62923.765 Da

References

Yard BA, Carter LG, Johnson KA, Overton IM, Dorward M, Liu H, McMahon SA, Oke M, Puech D, Barton GJ, Naismith JH, Campopiano DJ: The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis. J Mol Biol. 2007 Jul 27;370(5):870-86. Epub 2007 May 10. [17559874 ]

Target Details

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

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 ]

From T3DB