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Glycine (T3D4318)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (31)XML
Targets (31)
Record Information
Version2.0
Creation Date2014-08-29 06:21:32 UTC
Update Date2018-03-21 17:46:16 UTC
Accession NumberT3D4318
Identification
Common NameGlycine
ClassSmall Molecule
DescriptionGlycine is a simple, nonessential amino acid that in its pure form exists as a colorless, sweet-tasting crystalline solid. Glycine is the only achiral proteinogenic amino acid. While normally considered a non-essential amino acid, studies with rodent models show reduced growth on low-glycine diets. The average adult ingests 3 to 5 grams of glycine daily. Glycine is involved in the body's production of DNA, phospholipids and collagen, and in the production of energy. Glycine is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In the liver, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme), which can produce glycine from ammonia, carbon dioxide, methylene tetrahydrofolate and NADH. Glycine is degraded via three pathways. With the most common pathway being called the glycine cleavage system. The glycine cleavage enzyme system comprises four proteins: P-, T-, H- and L-proteins (EC 1.4.4.2, EC 2.1.2.10 and EC 1.8.1.4 for P-, T- and L-proteins). Mutations have been described in the GLDC (OMIM 238300), AMT (OMIM 238310), and GCSH (OMIM 238330) genes encoding the P-, T-, and H-proteins respectively. The glycine cleavage system catalyzes the oxidative conversion of glycine into carbon dioxide and ammonia, with the remaining one-carbon unit transferred to folate as methylenetetrahydrofolate. The principal function of glycine is as a precursor to proteins. Most proteins incorporate only small quantities although collagen contains about 35% glycine. Glycine is also an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP). There are a number of inborn errors of metabolism that are associated with elevated levels of glycine in the blood or urine. Nonketotic hyperglycinaemia (OMIM 606899) is an autosomal recessive condition caused by deficient enzyme activity of the glycine cleavage enzyme system (EC 2.1.1.10). It is the main catabolic pathway for glycine and it also contributes to one-carbon metabolism. Patients with a deficiency of this enzyme system have increased glycine in plasma, urine and cerebrospinal fluid (CSF) with an increased CSF: plasma glycine ratio (PMID 16151895). Glycine is also found to be associated with at least 12 other inborn errors of metabolism (IEMs) including: Citrullinemia Type I, Hyperglycinemia, non-ketotic, Hyperprolinemia Type I, Hyperprolinemia Type II, Iminoglycinuria, Isovaleric Aciduria, Malonic Aciduria, Methylmalonic Aciduria, Methylmalonic Aciduria Due to Cobalamin-Related Disorders, Non Ketotic Hyperglycinemeia, Prolinemia Type II, Propionic acidemia and Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency). When present in sufficiently high levels, glycine can be neurotoxin and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels as found in many of the IEMs mentioned above. Glycine is known to act as a neurotransmitter. Chronically elevated levels of glycine can lead to a build-up of glycine in the brain, which leads to abnormal neural signaling and a condition known as glycine encephalopathy. Affected infants experience a progressive lack of energy (lethargy), feeding difficulties, weak muscle tone (hypotonia), abnormal jerking movements, and life-threatening problems with breathing. Most children who survive these early signs and symptoms develop profound intellectual disability and seizures. Other atypical types of glycine encephalopathy appear later in childhood or adulthood and cause a variety of medical problems that primarily affect the nervous system.
Compound Type
  • Amine
  • Animal Toxin
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Glycine Agent
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Non-Essential Amino Acid
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2-Aminoacetate
2-Aminoacetic acid
Aciport
Amino-Acetate
Amino-Acetic acid
Aminoacetate
Aminoacetic acid
Aminoessigsaeure
Aminoethanoate
Aminoethanoic acid
G
Glicoamin
Gly
Glycin
Glycocoll
Glycolixir
Glycosthene
Glykokoll
Glyzin
Gyn-Hydralin
H2N-CH2-COOH
Hgly
Leimzucker
Padil
Chemical FormulaC2H5NO2
Average Molecular Mass75.067 g/mol
Monoisotopic Mass75.032 g/mol
CAS Registry Number56-40-6
IUPAC Name2-aminoacetic acid
Traditional Nameglycine
SMILESNCC(O)=O
InChI IdentifierInChI=1S/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5)
InChI KeyInChIKey=DHMQDGOQFOQNFH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids
Alternative Parents
Substituents
  • Alpha-amino acid
  • Amino acid
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Organic nitrogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Primary aliphatic amine
  • Organic oxygen compound
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Extracellular
  • Lysosome
  • Membrane
  • Mitochondria
  • Peroxisome
Biofluid LocationsNot Available
Tissue Locations
  • Bladder
  • Brain
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Myelin
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Spleen
  • Stratum Corneum
  • Thyroid Gland
Pathways
NameSMPDB LinkKEGG Link
Alanine MetabolismSMP00055 map00250
Ammonia RecyclingSMP00009 map00910
Bile Acid BiosynthesisSMP00035 Not Available
Carnitine SynthesisSMP00465 Not Available
Glutathione MetabolismSMP00015 map00480
Glycine and Serine MetabolismSMP00004 map00260
Methionine MetabolismSMP00033 map00270
Porphyrin MetabolismSMP00024 map00860
Citrullinemia Type ISMP00001 Not Available
Hyperglycinemia, non-ketoticSMP00485 Not Available
Hyperprolinemia Type ISMP00361 Not Available
Hyperprolinemia Type IISMP00360 Not Available
IminoglycinuriaSMP00193 Not Available
Isovaleric AciduriaSMP00238 Not Available
Malonic AciduriaSMP00198 Not Available
Methylmalonic AciduriaSMP00200 Not Available
Methylmalonic Aciduria Due to Cobalamin-Related DisordersSMP00201 Not Available
Non Ketotic HyperglycinemiaSMP00223 Not Available
Prolinemia Type IISMP00208 Not Available
Propionic AcidemiaSMP00236 Not Available
Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency)SMP00235 Not Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point262 dec°C
Boiling PointNot Available
Solubility2.49E+005 mg/L (at 25°C)
LogP-3.21
Predicted Properties
PropertyValueSource
Water Solubility552 g/LALOGPS
logP-3.3ALOGPS
logP-3.4ChemAxon
logS0.87ALOGPS
pKa (Strongest Acidic)2.31ChemAxon
pKa (Strongest Basic)9.24ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area63.32 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity16 m³·mol⁻¹ChemAxon
Polarizability6.65 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00dj-2900000000-0ef96bcf06ce475afcddView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-00dj-1900000000-1d289099ac79cfb8bb19View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00di-7910000000-6c972a683dfb75b69331View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0udi-0900000000-ef69e38ee6cebc2ece00View in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-00di-2910000000-3215b9e40f20c7b306cdView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-9000000000-719b7f248956f13a312dView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-0900000000-99b4fc43740b21edc786View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-1910000000-4cff4d14c73acff9442fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00dj-2900000000-0ef96bcf06ce475afcddView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00dj-1900000000-1d289099ac79cfb8bb19View in MoNA
GC-MSGC-MS Spectrum - GC-EI-QQ (Non-derivatized)splash10-0002-4960000000-2c6fa028e985c6019854View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-7910000000-6c972a683dfb75b69331View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-2910000000-3215b9e40f20c7b306cdView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0udi-0900000000-ef69e38ee6cebc2ece00View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00ds-2900000000-ffffed9c78c16a884e4aView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-004r-3900000000-f288b50b7b6890429811View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-1900000000-c76140c31c1f120e4b9dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-9000000000-f0a2cfbefb9fcd9b6c3eView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9300000000-b8bbfc1276d5adb1ba04View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-00di-9000000000-6001578fc511ba3fefefView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-00di-9000000000-79b2a0a9d93de6a62358View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-00di-9000000000-9290dbe208c4744f4431View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-6001578fc511ba3fefefView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-79b2a0a9d93de6a62358View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-9290dbe208c4744f4431View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-00di-9000000000-605b44ac311a9af4bb7aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-003r-9000000000-725357e461c898a7451eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9000000000-9f3930e66b117ad91dcaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-b3336097dddbb5e22871View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-6M) , Positivesplash10-001i-9000000000-719b7f248956f13a312dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-004i-9000000000-342ab462db0835abb3d2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-0ar1-9010000000-9daadc1d169a8530926dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-07y0-9220000000-8c7785f1f3aa8052679fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-0ula-9110000000-43ada06fe1b56b4e9fccView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-017i-9000000000-fbd78fbb48f082235f42View in MoNA
LC-MS/MSLC-MS/MS Spectrum - CE-ESI-TOF (CE-system connected to 6210 Time-of-Flight MS, Agilent) , Positivesplash10-004i-9000000000-c38d0fb28793438083a9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-Q-Exactive Plus , Positivesplash10-004i-9000000000-18a7ae48c7b0e15cdf18View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004i-9000000000-342ab462db0835abb3d2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0ar1-9010000000-9daadc1d169a8530926dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-07y0-9220000000-8c7785f1f3aa8052679fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0ula-9110000000-43ada06fe1b56b4e9fccView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-017i-9000000000-fbd78fbb48f082235f42View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-9000000000-89b2c043a5afe3ebc6f6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9000000000-b4046e208ee8adb87021View in MoNA
MSMass Spectrum (Electron Ionization)splash10-001i-9000000000-222d6c3a1ba6afcd7ea9View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureAbsorbed from the small intestine via an active transport mechanism.
Mechanism of ToxicityIn the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia.
Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.
MetabolismHepatic
Toxicity ValuesORL-RAT LD50 7930 mg/kg, SCU-RAT LD50 5200 mg/kg, IVN-RAT LD50 2600 mg/kg, ORL-MUS LD50 4920 mg/kg
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesSupplemental glycine may have antispastic activity. Very early findings suggest it may also have antipsychotic activity as well as antioxidant and anti-inflammatory activities.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of glycine are associated with at least 12 inborn errors of metabolism including: Citrullinemia Type I, Hyperglycinemia, non-ketotic, Hyperprolinemia Type I, Hyperprolinemia Type II, Iminoglycinuria, Isovaleric Aciduria, Malonic Aciduria, Methylmalonic Aciduria, Methylmalonic Aciduria Due to Cobalamin-Related Disorders, Non Ketotic Hyperglycinemeia, Prolinemia Type II, Propionic academia and Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency).
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00145
HMDB IDHMDB00123
PubChem Compound ID750
ChEMBL IDCHEMBL773
ChemSpider ID730
KEGG IDC00037
UniProt IDNot Available
OMIM ID
ChEBI ID15428
BioCyc IDGLY
CTD IDNot Available
Stitch IDNot Available
PDB IDGLY
ACToR IDNot Available
Wikipedia LinkGlycine
References
Synthesis Reference

Koichi Niimura, Takako Kawabe, Takao Ando, Kenichi Saito, “Phenylalanine-glycine compounds having anti-tumor activity, process for preparation thereof, and pharmaceutical composition containing said compounds.” U.S. Patent US5411964, issued August, 1908.

MSDSLink
General References
  1. Van Hove JL, Vande Kerckhove K, Hennermann JB, Mahieu V, Declercq P, Mertens S, De Becker M, Kishnani PS, Jaeken J: Benzoate treatment and the glycine index in nonketotic hyperglycinaemia. J Inherit Metab Dis. 2005;28(5):651-63. [16151895 ]
  2. Christie GR, Ford D, Howard A, Clark MA, Hirst BH: Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1. Gastroenterology. 2001 Feb;120(2):439-48. [11159884 ]
  3. Jones CM, Smith M, Henderson MJ: Reference data for cerebrospinal fluid and the utility of amino acid measurement for the diagnosis of inborn errors of metabolism. Ann Clin Biochem. 2006 Jan;43(Pt 1):63-6. [16390611 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. Bennett FI, Jackson AA: Glycine is not formed through the amino transferase reaction in human or rat placenta. Placenta. 1998 May;19(4):329-31. [9639330 ]
  8. Gomeza J, Ohno K, Hulsmann S, Armsen W, Eulenburg V, Richter DW, Laube B, Betz H: Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. Neuron. 2003 Nov 13;40(4):797-806. [14622583 ]
  9. Collins JW, Macdermott S, Bradbrook RA, Keeley FX Jr, Timoney AG: Is using ethanol-glycine irrigating fluid monitoring and 'good surgical practice' enough to prevent harmful absorption during transurethral resection of the prostate? BJU Int. 2006 Jun;97(6):1247-51. [16686720 ]
  10. Boneh A, Degani Y, Harari M: Prognostic clues and outcome of early treatment of nonketotic hyperglycinemia. Pediatr Neurol. 1996 Sep;15(2):137-41. [8888048 ]
  11. Dicke JM, Verges D, Kelley LK, Smith CH: Glycine uptake by microvillous and basal plasma membrane vesicles from term human placentae. Placenta. 1993 Jan-Feb;14(1):85-92. [8456092 ]
  12. 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 ]
  13. Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. [2026685 ]
  14. 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 ]
  15. Prescot AP, de B Frederick B, Wang L, Brown J, Jensen JE, Kaufman MJ, Renshaw PF: In vivo detection of brain glycine with echo-time-averaged (1)H magnetic resonance spectroscopy at 4.0 T. Magn Reson Med. 2006 Mar;55(3):681-6. [16453318 ]
  16. Byard RW, Harrison R, Wells R, Gilbert JD: Glycine toxicity and unexpected intra-operative death. J Forensic Sci. 2001 Sep;46(5):1244-6. [11569574 ]
  17. 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 ]
  18. Khan SA, Cox IJ, Hamilton G, Thomas HC, Taylor-Robinson SD: In vivo and in vitro nuclear magnetic resonance spectroscopy as a tool for investigating hepatobiliary disease: a review of H and P MRS applications. Liver Int. 2005 Apr;25(2):273-81. [15780050 ]
  19. Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ: Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem. 1984 Mar;30(3):426-32. [6321058 ]
  20. 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 ]
  21. 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 GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Glutamate receptor ionotropic, NMDA 2A
General Function:
Zinc ion binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.
Gene Name:
GRIN2A
Uniprot ID:
Q12879
Molecular Weight:
165281.215 Da
References
  1. Liu Y, Wong TP, Aarts M, Rooyakkers A, Liu L, Lai TW, Wu DC, Lu J, Tymianski M, Craig AM, Wang YT: NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. J Neurosci. 2007 Mar 14;27(11):2846-57. [17360906 ]
  2. Domingues A, Almeida S, da Cruz e Silva EF, Oliveira CR, Rego AC: Toxicity of beta-amyloid in HEK293 cells expressing NR1/NR2A or NR1/NR2B N-methyl-D-aspartate receptor subunits. Neurochem Int. 2007 May;50(6):872-80. Epub 2007 Mar 7. [17403555 ]
  3. Brosnan RJ, Yang L, Milutinovic PS, Zhao J, Laster MJ, Eger EI 2nd, Sonner JM: Ammonia has anesthetic properties. Anesth Analg. 2007 Jun;104(6):1430-3, table of contents. [17513636 ]
  4. Milutinovic PS, Yang L, Cantor RS, Eger EI 2nd, Sonner JM: Anesthetic-like modulation of a gamma-aminobutyric acid type A, strychnine-sensitive glycine, and N-methyl-d-aspartate receptors by coreleased neurotransmitters. Anesth Analg. 2007 Aug;105(2):386-92. [17646495 ]
  5. Gabra BH, Kessler FK, Ritter JK, Dewey WL, Smith FL: Decrease in N-methyl-D-aspartic acid receptor-NR2B subunit levels by intrathecal short-hairpin RNA blocks group I metabotropic glutamate receptor-mediated hyperalgesia. J Pharmacol Exp Ther. 2007 Jul;322(1):186-94. Epub 2007 Apr 3. [17405869 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
2. 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
TypeValueAssay TypeAssay Source
Inhibitory5100 uMNot AvailableBindingDB 18133
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Bermingham JR Jr, Pennington J: Organization and expression of the SLC36 cluster of amino acid transporter genes. Mamm Genome. 2004 Feb;15(2):114-25. [15058382 ]
  4. Broer A, Cavanaugh JA, Rasko JE, Broer S: The molecular basis of neutral aminoacidurias. Pflugers Arch. 2006 Jan;451(4):511-7. Epub 2005 Jul 29. [16052352 ]
  5. Metzner L, Kalbitz J, Brandsch M: Transport of pharmacologically active proline derivatives by the human proton-coupled amino acid transporter hPAT1. J Pharmacol Exp Ther. 2004 Apr;309(1):28-35. Epub 2004 Jan 12. [14718599 ]
  6. 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 ]
Target Details
3. 5-aminolevulinate synthase, erythroid-specific, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
ALAS2
Uniprot ID:
P22557
Molecular Weight:
64632.86 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Hungerer C, Troup B, Romling U, Jahn D: Regulation of the hemA gene during 5-aminolevulinic acid formation in Pseudomonas aeruginosa. J Bacteriol. 1995 Mar;177(6):1435-43. [7883699 ]
  4. Shoolingin-Jordan PM, Al-Daihan S, Alexeev D, Baxter RL, Bottomley SS, Kahari ID, Roy I, Sarwar M, Sawyer L, Wang SF: 5-Aminolevulinic acid synthase: mechanism, mutations and medicine. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):361-6. [12686158 ]
  5. Munakata H, Yamagami T, Nagai T, Yamamoto M, Hayashi N: Purification and structure of rat erythroid-specific delta-aminolevulinate synthase. J Biochem. 1993 Jul;114(1):103-11. [8407861 ]
Target Details
4. Glutamate receptor ionotropic, NMDA 2C
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN2C
Uniprot ID:
Q14957
Molecular Weight:
134207.77 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Widdowson PS, Gyte AJ, Upton R, Wyatt I: Failure of glycine site NMDA receptor antagonists to protect against L-2-chloropropionic acid-induced neurotoxicity highlights the uniqueness of cerebellar NMDA receptors. Brain Res. 1996 Nov 4;738(2):236-42. [8955518 ]
  4. Al-Ghoul WM, Meeker RB, Greenwood RS: Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in vasopressin and oxytocin neuroendocrine cells. Brain Res Mol Brain Res. 1997 Mar;44(2):262-72. [9073168 ]
  5. Malayev A, Gibbs TT, Farb DH: Inhibition of the NMDA response by pregnenolone sulphate reveals subtype selective modulation of NMDA receptors by sulphated steroids. Br J Pharmacol. 2002 Feb;135(4):901-9. [11861317 ]
Target Details
5. Glutathione synthetase
General Function:
Protein homodimerization activity
Specific Function:
Not Available
Gene Name:
GSS
Uniprot ID:
P48637
Molecular Weight:
52384.325 Da
References
  1. Herrera K, Cahoon RE, Kumaran S, Jez J: Reaction mechanism of glutathione synthetase from Arabidopsis thaliana: site-directed mutagenesis of active site residues. J Biol Chem. 2007 Jun 8;282(23):17157-65. Epub 2007 Apr 22. [17452339 ]
  2. Ducruix C, Junot C, Fievet JB, Villiers F, Ezan E, Bourguignon J: New insights into the regulation of phytochelatin biosynthesis in A. thaliana cells from metabolite profiling analyses. Biochimie. 2006 Nov;88(11):1733-42. Epub 2006 Sep 7. [16996193 ]
  3. Ristoff E, Larsson A: Inborn errors in the metabolism of glutathione. Orphanet J Rare Dis. 2007 Mar 30;2:16. [17397529 ]
  4. Pai CH, Chiang BY, Ko TP, Chou CC, Chong CM, Yen FJ, Chen S, Coward JK, Wang AH, Lin CH: Dual binding sites for translocation catalysis by Escherichia coli glutathionylspermidine synthetase. EMBO J. 2006 Dec 13;25(24):5970-82. Epub 2006 Nov 23. [17124497 ]
  5. Janaky R, Dohovics R, Saransaari P, Oja SS: Modulation of [3H]dopamine release by glutathione in mouse striatal slices. Neurochem Res. 2007 Aug;32(8):1357-64. Epub 2007 Mar 31. [17401648 ]
Target Details
6. Glycine--tRNA ligase
General Function:
Protein dimerization activity
Specific Function:
Catalyzes the attachment of glycine to tRNA(Gly). Is also able produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs.
Gene Name:
GARS
Uniprot ID:
P41250
Molecular Weight:
83164.83 Da
References
  1. Okamoto K, Kuno A, Hasegawa T: Recognition sites of glycine tRNA for glycyl-tRNA synthetase from hyperthermophilic archaeon, Aeropyrum pernix K1. Nucleic Acids Symp Ser (Oxf). 2005;(49):299-300. [17150752 ]
  2. Tsang SW, Vinters HV, Cummings JL, Wong PT, Chen CP, Lai MK: Alterations in NMDA receptor subunit densities and ligand binding to glycine recognition sites are associated with chronic anxiety in Alzheimer's disease. Neurobiol Aging. 2008 Oct;29(10):1524-32. Epub 2007 Apr 11. [17433503 ]
  3. Scherer SS: Inherited neuropathies: new genes don't fit old models. Neuron. 2006 Sep 21;51(6):672-4. [16982409 ]
  4. Cader MZ, Ren J, James PA, Bird LE, Talbot K, Stammers DK: Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy. FEBS Lett. 2007 Jun 26;581(16):2959-64. Epub 2007 May 29. [17544401 ]
  5. Antonellis A, Lee-Lin SQ, Wasterlain A, Leo P, Quezado M, Goldfarb LG, Myung K, Burgess S, Fischbeck KH, Green ED: Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons. J Neurosci. 2006 Oct 11;26(41):10397-406. [17035524 ]
Target Details
7. Serine hydroxymethyltransferase
General Function:
Pyridoxal phosphate binding
Specific Function:
Interconversion of serine and glycine.
Gene Name:
Not Available
Uniprot ID:
Q53ET4
Molecular Weight:
55973.345 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Bouwman RA, Musters RJ, van Beek-Harmsen BJ, de Lange JJ, Lamberts RR, Loer SA, Boer C: Sevoflurane-induced cardioprotection depends on PKC-alpha activation via production of reactive oxygen species. Br J Anaesth. 2007 Nov;99(5):639-45. Epub 2007 Sep 27. [17905752 ]
  4. Chang WN, Tsai JN, Chen BH, Huang HS, Fu TF: Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37. Epub 2007 Jul 30. [17664250 ]
  5. Kon K, Ikejima K, Okumura K, Aoyama T, Arai K, Takei Y, Lemasters JJ, Sato N: Role of apoptosis in acetaminophen hepatotoxicity. J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S49-52. [17567465 ]
Target Details
8. Serine hydroxymethyltransferase, cytosolic
General Function:
Serine binding
Specific Function:
Interconversion of serine and glycine.
Gene Name:
SHMT1
Uniprot ID:
P34896
Molecular Weight:
53082.18 Da
References
  1. Vatsyayan R, Roy U: Molecular cloning and biochemical characterization of Leishmania donovani serine hydroxymethyltransferase. Protein Expr Purif. 2007 Apr;52(2):433-40. Epub 2006 Oct 26. [17142057 ]
  2. Rajinikanth M, Harding SA, Tsai CJ: The glycine decarboxylase complex multienzyme family in Populus. J Exp Bot. 2007;58(7):1761-70. Epub 2007 Mar 12. [17355947 ]
  3. Chang WN, Tsai JN, Chen BH, Huang HS, Fu TF: Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37. Epub 2007 Jul 30. [17664250 ]
  4. Nijhout HF, Reed MC, Lam SL, Shane B, Gregory JF 3rd, Ulrich CM: In silico experimentation with a model of hepatic mitochondrial folate metabolism. Theor Biol Med Model. 2006 Dec 6;3:40. [17150100 ]
  5. Gagnon D, Foucher A, Girard I, Ouellette M: Stage specific gene expression and cellular localization of two isoforms of the serine hydroxymethyltransferase in the protozoan parasite Leishmania. Mol Biochem Parasitol. 2006 Nov;150(1):63-71. Epub 2006 Jul 13. [16876889 ]
Target Details
9. Sodium- and chloride-dependent glycine transporter 1
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May play a role in regulation of glycine levels in NMDA receptor-mediated neurotransmission.
Gene Name:
SLC6A9
Uniprot ID:
P48067
Molecular Weight:
78259.625 Da
References
  1. Wiles AL, Pearlman RJ, Rosvall M, Aubrey KR, Vandenberg RJ: N-Arachidonyl-glycine inhibits the glycine transporter, GLYT2a. J Neurochem. 2006 Nov;99(3):781-6. Epub 2006 Aug 8. [16899062 ]
  2. Lindsley CW, Wolkenberg SE, Kinney GG: Progress in the preparation and testing of glycine transporter type-1 (GlyT1) inhibitors. Curr Top Med Chem. 2006;6(17):1883-96. [17017963 ]
  3. Igartua I, Solis JM, Bustamante J: Glycine-induced long-term synaptic potentiation is mediated by the glycine transporter GLYT1. Neuropharmacology. 2007 Jun;52(8):1586-95. Epub 2007 Mar 14. [17462677 ]
  4. Sur C, Kinney GG: Glycine transporter 1 inhibitors and modulation of NMDA receptor-mediated excitatory neurotransmission. Curr Drug Targets. 2007 May;8(5):643-9. [17504107 ]
  5. Raiteri L, Stigliani S, Usai C, Diaspro A, Paluzzi S, Milanese M, Raiteri M, Bonanno G: Functional expression of release-regulating glycine transporters GLYT1 on GABAergic neurons and GLYT2 on astrocytes in mouse spinal cord. Neurochem Int. 2008 Jan;52(1-2):103-12. Epub 2007 May 16. [17597258 ]
Target Details
10. Alanine--glyoxylate aminotransferase 2, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Can metabolize asymmetric dimethylarginine (ADMA) via transamination to alpha-keto-delta-(NN-dimethylguanidino) valeric acid (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) synthase, and this activity provides mechanism through which the kidney regulates blood pressure.
Gene Name:
AGXT2
Uniprot ID:
Q9BYV1
Molecular Weight:
57155.905 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Baker PR, Cramer SD, Kennedy M, Assimos DG, Holmes RP: Glycolate and glyoxylate metabolism in HepG2 cells. Am J Physiol Cell Physiol. 2004 Nov;287(5):C1359-65. Epub 2004 Jul 7. [15240345 ]
  4. Takada Y, Mori T, Noguchi T: The effect of vitamin B6 deficiency on alanine: glyoxylate aminotransferase isoenzymes in rat liver. Arch Biochem Biophys. 1984 Feb 15;229(1):1-6. [6703688 ]
Target Details
11. Bile acid-CoA:amino acid N-acyltransferase
General Function:
Very long chain acyl-coa hydrolase activity
Specific Function:
Involved in bile acid metabolism. In liver hepatocytes catalyzes the second step in the conjugation of C24 bile acids (choloneates) to glycine and taurine before excretion into bile canaliculi. The major components of bile are cholic acid and chenodeoxycholic acid. In a first step the bile acids are converted to an acyl-CoA thioester, either in peroxisomes (primary bile acids deriving from the cholesterol pathway), or cytoplasmic at the endoplasmic reticulum (secondary bile acids). May catalyze the conjugation of primary or secondary bile acids, or both. The conjugation increases the detergent properties of bile acids in the intestine, which facilitates lipid and fat-soluble vitamin absorption. In turn, bile acids are deconjugated by bacteria in the intestine and are recycled back to the liver for reconjugation (secondary bile acids). May also act as an acyl-CoA thioesterase that regulates intracellular levels of free fatty acids. In vitro, catalyzes the hydrolysis of long- and very long-chain saturated acyl-CoAs to the free fatty acid and coenzyme A (CoASH), and conjugates glycine to these acyl-CoAs.
Gene Name:
BAAT
Uniprot ID:
Q14032
Molecular Weight:
46298.865 Da
References
  1. Styles NA, Falany JL, Barnes S, Falany CN: Quantification and regulation of the subcellular distribution of bile acid coenzyme A:amino acid N-acyltransferase activity in rat liver. J Lipid Res. 2007 Jun;48(6):1305-15. Epub 2007 Mar 22. [17379925 ]
  2. Visser WF, van Roermund CW, Ijlst L, Waterham HR, Wanders RJ: Demonstration of bile acid transport across the mammalian peroxisomal membrane. Biochem Biophys Res Commun. 2007 Jun 1;357(2):335-40. Epub 2007 Mar 26. [17416343 ]
  3. Pellicoro A, van den Heuvel FA, Geuken M, Moshage H, Jansen PL, Faber KN: Human and rat bile acid-CoA:amino acid N-acyltransferase are liver-specific peroxisomal enzymes: implications for intracellular bile salt transport. Hepatology. 2007 Feb;45(2):340-8. [17256745 ]
  4. Nakamura K, Morrison SF: Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R127-36. Epub 2006 Aug 24. [16931649 ]
Target Details
12. Glycine N-methyltransferase
General Function:
Glycine n-methyltransferase activity
Specific Function:
Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
Gene Name:
GNMT
Uniprot ID:
Q14749
Molecular Weight:
32742.0 Da
References
  1. Soriano A, Castillo R, Christov C, Andres J, Moliner V, Tunon I: Catalysis in glycine N-methyltransferase: testing the electrostatic stabilization and compression hypothesis. Biochemistry. 2006 Dec 19;45(50):14917-25. [17154529 ]
  2. Luka Z, Pakhomova S, Loukachevitch LV, Egli M, Newcomer ME, Wagner C: 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. J Biol Chem. 2007 Feb 9;282(6):4069-75. Epub 2006 Dec 7. [17158459 ]
  3. Velichkova P, Himo F: Methyl transfer in glycine N-methyltransferase. A theoretical study. J Phys Chem B. 2005 Apr 28;109(16):8216-9. [16851960 ]
Target Details
13. Glycine dehydrogenase (decarboxylating), mitochondrial
General Function:
Lyase activity
Specific Function:
The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH).
Gene Name:
GLDC
Uniprot ID:
P23378
Molecular Weight:
112728.805 Da
References
  1. Mukherjee M, Brown MT, McArthur AG, Johnson PJ: Proteins of the glycine decarboxylase complex in the hydrogenosome of Trichomonas vaginalis. Eukaryot Cell. 2006 Dec;5(12):2062-71. [17158739 ]
  2. Kanno J, Hutchin T, Kamada F, Narisawa A, Aoki Y, Matsubara Y, Kure S: Genomic deletion within GLDC is a major cause of non-ketotic hyperglycinaemia. J Med Genet. 2007 Mar;44(3):e69. [17361008 ]
  3. Engel N, van den Daele K, Kolukisaoglu U, Morgenthal K, Weckwerth W, Parnik T, Keerberg O, Bauwe H: Deletion of glycine decarboxylase in Arabidopsis is lethal under nonphotorespiratory conditions. Plant Physiol. 2007 Jul;144(3):1328-35. Epub 2007 May 11. [17496108 ]
Target Details
14. Glycine receptor subunit alpha-2
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA2
Uniprot ID:
P23416
Molecular Weight:
52001.585 Da
References
  1. Young-Pearse TL, Ivic L, Kriegstein AR, Cepko CL: Characterization of mice with targeted deletion of glycine receptor alpha 2. Mol Cell Biol. 2006 Aug;26(15):5728-34. [16847326 ]
  2. Qi Z, Stephens NR, Spalding EP: Calcium entry mediated by GLR3.3, an Arabidopsis glutamate receptor with a broad agonist profile. Plant Physiol. 2006 Nov;142(3):963-71. Epub 2006 Sep 29. [17012403 ]
  3. Majumdar S, Heinze L, Haverkamp S, Ivanova E, Wassle H: Glycine receptors of A-type ganglion cells of the mouse retina. Vis Neurosci. 2007 Jul-Aug;24(4):471-87. Epub 2007 May 29. [17550639 ]
Target Details
15. Serine hydroxymethyltransferase, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Interconversion of serine and glycine. Associates with mitochondrial DNA.
Gene Name:
SHMT2
Uniprot ID:
P34897
Molecular Weight:
55992.385 Da
References
  1. Gagnon D, Foucher A, Girard I, Ouellette M: Stage specific gene expression and cellular localization of two isoforms of the serine hydroxymethyltransferase in the protozoan parasite Leishmania. Mol Biochem Parasitol. 2006 Nov;150(1):63-71. Epub 2006 Jul 13. [16876889 ]
  2. Vatsyayan R, Roy U: Molecular cloning and biochemical characterization of Leishmania donovani serine hydroxymethyltransferase. Protein Expr Purif. 2007 Apr;52(2):433-40. Epub 2006 Oct 26. [17142057 ]
  3. Rajinikanth M, Harding SA, Tsai CJ: The glycine decarboxylase complex multienzyme family in Populus. J Exp Bot. 2007;58(7):1761-70. Epub 2007 Mar 12. [17355947 ]
Target Details
16. Serine--pyruvate aminotransferase
General Function:
Transaminase activity
Specific Function:
Not Available
Gene Name:
AGXT
Uniprot ID:
P21549
Molecular Weight:
43009.535 Da
References
  1. Ricoult C, Echeverria LO, Cliquet JB, Limami AM: Characterization of alanine aminotransferase (AlaAT) multigene family and hypoxic response in young seedlings of the model legume Medicago truncatula. J Exp Bot. 2006;57(12):3079-89. Epub 2006 Aug 9. [16899523 ]
  2. Han Q, Robinson H, Gao YG, Vogelaar N, Wilson SR, Rizzi M, Li J: Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase. J Biol Chem. 2006 Dec 1;281(48):37175-82. Epub 2006 Sep 21. [16990263 ]
  3. Lu TC, Ko YZ, Huang HW, Hung YC, Lin YC, Peng WH: Analgesic and anti-inflammatory activities of aqueous extract from Glycine tomentella root in mice. J Ethnopharmacol. 2007 Aug 15;113(1):142-8. Epub 2007 May 31. [17616291 ]
Target Details
17. Vesicular inhibitory amino acid transporter
General Function:
Glycine transmembrane transporter activity
Specific Function:
Involved in the uptake of GABA and glycine into the synaptic vesicles.
Gene Name:
SLC32A1
Uniprot ID:
Q9H598
Molecular Weight:
57414.58 Da
References
  1. Fujii M, Arata A, Kanbara-Kume N, Saito K, Yanagawa Y, Obata K: Respiratory activity in brainstem of fetal mice lacking glutamate decarboxylase 65/67 and vesicular GABA transporter. Neuroscience. 2007 May 25;146(3):1044-52. Epub 2007 Apr 5. [17418495 ]
  2. Aubrey KR, Rossi FM, Ruivo R, Alboni S, Bellenchi GC, Le Goff A, Gasnier B, Supplisson S: The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype. J Neurosci. 2007 Jun 6;27(23):6273-81. [17554001 ]
  3. Uchigashima M, Fukaya M, Watanabe M, Kamiya H: Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus. J Neurosci. 2007 Jul 25;27(30):8088-100. [17652600 ]
Target Details
18. 5-aminolevulinate synthase, nonspecific, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
ALAS1
Uniprot ID:
P13196
Molecular Weight:
70580.325 Da
References
  1. Turbeville TD, Zhang J, Hunter GA, Ferreira GC: Histidine 282 in 5-aminolevulinate synthase affects substrate binding and catalysis. Biochemistry. 2007 May 22;46(20):5972-81. Epub 2007 May 1. [17469798 ]
  2. He XM, Zhou J, Cheng Y, Fan J: [Purification and production of the extracellular 5-aminolevulinate from recombiniant Escherichia coli expressing yeast ALAS]. Sheng Wu Gong Cheng Xue Bao. 2007 May;23(3):520-4. [17578005 ]
Target Details
19. Glycine N-acyltransferase
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently. Can conjugate numerous substrates to form a variety of N-acylglycines, with a preference for benzoyl-CoA over phenylacetyl-CoA as acyl donors. Thereby detoxify xenobiotics, such as benzoic acid or salicylic acid, and endogenous organic acids, such as isovaleric acid.
Gene Name:
GLYAT
Uniprot ID:
Q6IB77
Molecular Weight:
33923.995 Da
References
  1. Narasipura SD, Ren P, Dyavaiah M, Auger I, Chaturvedi V, Chaturvedi S: An efficient method for homologous gene reconstitution in Cryptococcus gattii using URA5 auxotrophic marker. Mycopathologia. 2006 Dec;162(6):401-9. [17146584 ]
  2. Zhou CX, Gao Y: Frequent genetic alterations and reduced expression of the Axin1 gene in oral squamous cell carcinoma: involvement in tumor progression and metastasis. Oncol Rep. 2007 Jan;17(1):73-9. [17143481 ]
Target Details
20. Glycine N-acyltransferase-like protein 1
General Function:
Glycine n-acyltransferase activity
Specific Function:
Acyltransferase which transfers an acyl group to the N-terminus of glutamine. Can use phenylacetyl-CoA as an acyl donor.
Gene Name:
GLYATL1
Uniprot ID:
Q969I3
Molecular Weight:
35100.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
21. Glycine N-acyltransferase-like protein 2
General Function:
Glycine n-acyltransferase activity
Specific Function:
Mitochondrial acyltransferase which transfers the acyl group to the N-terminus of glycine. Conjugates numerous substrates, such as arachidonoyl-CoA and saturated medium and long-chain acyl-CoAs ranging from chain-length C8:0-CoA to C18:0-CoA, to form a variety of N-acylglycines. Shows a preference for monounsaturated fatty acid oleoyl-CoA (C18:1-CoA) as an acyl donor. Does not exhibit any activity toward C22:6-CoA and chenodeoxycholoyl-CoA, nor toward serine or alanine.
Gene Name:
GLYATL2
Uniprot ID:
Q8WU03
Molecular Weight:
34277.055 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
22. Glycine amidinotransferase, mitochondrial
General Function:
Glycine amidinotransferase activity
Specific Function:
Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.
Gene Name:
GATM
Uniprot ID:
P50440
Molecular Weight:
48455.01 Da
References
  1. Wang L, Zhang Y, Shao M, Zhang H: Spatiotemporal expression of the creatine metabolism related genes agat, gamt and ct1 during zebrafish embryogenesis. Int J Dev Biol. 2007;51(3):247-53. [17486546 ]
  2. Dutta U, Cohenford MA, Guha M, Dain JA: Non-enzymatic interactions of glyoxylate with lysine, arginine, and glucosamine: a study of advanced non-enzymatic glycation like compounds. Bioorg Chem. 2007 Feb;35(1):11-24. Epub 2006 Sep 12. [16970975 ]
Target Details
23. Glycine receptor subunit alpha-1
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA1
Uniprot ID:
P23415
Molecular Weight:
52623.35 Da
References
  1. Heinze L, Harvey RJ, Haverkamp S, Wassle H: Diversity of glycine receptors in the mouse retina: localization of the alpha4 subunit. J Comp Neurol. 2007 Feb 1;500(4):693-707. [17154252 ]
  2. Eulenburg V, Becker K, Gomeza J, Schmitt B, Becker CM, Betz H: Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. Biochem Biophys Res Commun. 2006 Sep 22;348(2):400-5. Epub 2006 Jul 26. [16884688 ]
Target Details
24. Glycine receptor subunit alpha-3
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA3
Uniprot ID:
O75311
Molecular Weight:
53799.775 Da
References
  1. Heinze L, Harvey RJ, Haverkamp S, Wassle H: Diversity of glycine receptors in the mouse retina: localization of the alpha4 subunit. J Comp Neurol. 2007 Feb 1;500(4):693-707. [17154252 ]
  2. Majumdar S, Heinze L, Haverkamp S, Ivanova E, Wassle H: Glycine receptors of A-type ganglion cells of the mouse retina. Vis Neurosci. 2007 Jul-Aug;24(4):471-87. Epub 2007 May 29. [17550639 ]
Target Details
25. N-arachidonyl glycine receptor
General Function:
G-protein coupled receptor activity
Specific Function:
Receptor for N-arachidonyl glycine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. May contribute to regulation of the immune system.
Gene Name:
GPR18
Uniprot ID:
Q14330
Molecular Weight:
38133.27 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
26. Peroxisomal sarcosine oxidase
General Function:
Sarcosine oxidase activity
Specific Function:
Metabolizes sarcosine, L-pipecolic acid and L-proline.
Gene Name:
PIPOX
Uniprot ID:
Q9P0Z9
Molecular Weight:
44065.515 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
27. 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
GCAT
Uniprot ID:
O75600
Molecular Weight:
45284.6 Da
References
  1. Bashir Q, Rashid N, Akhtar M: Mechanism and substrate stereochemistry of 2-amino-3-oxobutyrate CoA ligase: implications for 5-aminolevulinate synthase and related enzymes. Chem Commun (Camb). 2006 Dec 28;(48):5065-7. Epub 2006 Oct 13. [17146529 ]
Target Details
28. Glutamate receptor ionotropic, NMDA 3B
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN3B
Uniprot ID:
O60391
Molecular Weight:
112990.98 Da
References
  1. Smothers CT, Woodward JJ: Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits. J Pharmacol Exp Ther. 2007 Aug;322(2):739-48. Epub 2007 May 14. [17502428 ]
Target Details
29. Glycine cleavage system H protein, mitochondrial
General Function:
Aminomethyltransferase activity
Specific Function:
The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).
Gene Name:
GCSH
Uniprot ID:
P23434
Molecular Weight:
18884.37 Da
References
  1. Kanno J, Hutchin T, Kamada F, Narisawa A, Aoki Y, Matsubara Y, Kure S: Genomic deletion within GLDC is a major cause of non-ketotic hyperglycinaemia. J Med Genet. 2007 Mar;44(3):e69. [17361008 ]
Target Details
30. Glycine receptor subunit beta
General Function:
Glycine binding
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRB
Uniprot ID:
P48167
Molecular Weight:
56121.62 Da
References
  1. Eulenburg V, Becker K, Gomeza J, Schmitt B, Becker CM, Betz H: Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. Biochem Biophys Res Commun. 2006 Sep 22;348(2):400-5. Epub 2006 Jul 26. [16884688 ]
Target Details
31. Sodium- and chloride-dependent glycine transporter 2
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May be responsible for the termination of neurotransmission at strychnine-sensitive glycinergic synapses.
Gene Name:
SLC6A5
Uniprot ID:
Q9Y345
Molecular Weight:
87433.13 Da
References
  1. Eulenburg V, Becker K, Gomeza J, Schmitt B, Becker CM, Betz H: Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. Biochem Biophys Res Commun. 2006 Sep 22;348(2):400-5. Epub 2006 Jul 26. [16884688 ]