Biomarker: glycine

Histology type: endometrial carcinoma

Stage: risk

Country: ten European countries

Region: EPIC study

Study type: Observational Study

Followed up time :

Cohort statistics: Average

Description: These findings suggest that variation in levels of glycine may represent specific pathways linked to endometrial cancer development. If causal, these pathway may offer novel targets for endometrial cancer prevention.

Sample type : serum

Sample method: liquid chromatography-mass spectrometry

Subgroup 1 age: 63.0±7.9

Expression figure legend: Odds ratios (ORs) and P-values for the associations between metabolites and risk of endometrial cancer in (A) unadjusted models (B) BMI-adjusted models&Odds ratios (ORs) and P-values for the associations between metabolite ratios and risk of endometrial cancer in (A) unadjusted models (B) BMI-adjusted models.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336647/figure/f0005/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336647/figure/f0010/

Status: Detected and Quantified

HMDB ID: HMDB0000123

Secondary accession numbers: HMDB00123

Common name: Glycine

Description: Glycine (Gly), is an alpha-amino acid. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon). Amino acids are organic compounds that contain amino (-NH2) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. Glycine is one of 20 proteinogenic amino acids, i.e., the amino acids used in the biosynthesis of proteins. Glycine is found in all organisms ranging from bacteria to plants to animals. It is classified as an aliphatic, non-polar amino acid and is the simplest of all amino acids. In humans, glycine is a nonessential amino acid, although experimental animals show reduced growth on low-glycine diets. The average adult human ingests 3 to 5 grams of glycine daily. Glycine is a colorless, sweet-tasting crystalline solid. It is the only achiral proteinogenic amino acid. Glycine was discovered in 1820 by the French chemist Henri Braconnot when he hydrolyzed gelatin by boiling it with sulfuric acid. The name comes from the Greek word glucus or "sweet tasting". Glycine is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme). In addition to being synthesized from serine, glycine can also be derived from threonine, choline or hydroxyproline via inter-organ metabolism of the liver and kidneys. Glycine is degraded via three pathways. The predominant pathway in animals and plants is the reverse of the glycine synthase pathway. In this context, the enzyme system involved glycine metabolism is called the glycine cleavage system. 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. 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 levels are effectively measured in plasma in both normal patients and those with inborn errors of glycine metabolism (http://www.dcnutrition.com/AminoAcids/). 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). 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. Glycine is involved in the body's production of DNA, hemoglobin, and collagen, and in the release of energy. The principal function of glycine is as a precursor to proteins. Most proteins incorporate only small quantities of glycine, a notable exception being collagen, which contains about 35% glycine. In higher eukaryotes, delta-aminolevulinic acid, the key precursor to porphyrins (needed for hemoglobin and cytochromes), is biosynthesized from glycine and succinyl-CoA by the enzyme ALA synthase. Glycine provides the central C2N subunit of all purines, which are key constituents of DNA and RNA. Glycine is 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).

Chemical formula: C2H5NO2

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).

Chemical taxonomy kingdom: Organic compounds

Chemical taxonomy super class: Organic acids and derivatives

Chemical taxonomy class: Carboxylic acids and derivatives

Chemical taxonomy sub class: Amino acids, peptides, and analogues

Direct parent: Alpha amino acids

Alternative parents: Amino acids Monocarboxylic acids and derivatives Carboxylic acids Organopnictogen compounds Organic oxides Monoalkylamines Hydrocarbon derivatives Carbonyl compounds

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 framework: Aliphatic acyclic compounds

Physiological effect: Genetic disorder Any disorder which has a direct genetic cause Inborn errors of metabolism 3-phosphoglycerate dehydrogenase deficiency 5-oxoprolinuria Acute intermittent porphyria (PMID: 10905759 , PMID: 10905759 , PMID: 18804642 , +3 More ) Adenosine deaminase deficiency Adenylosuccinate lyase deficiency (PMID: 11805243 , PMID: 12535838 , PMID: 15571235 , +2 More ) Dimethylglycine dehydrogenase deficiency Glycine n-methyltransferase deficiency Methionine adenosyltransferase deficiency (PMID: 8745393 , PMID: 27207470 , PMID: 27294788 , +6 More ) Myoadenylate deaminase deficiency (PMID: 11978597 ) Purine nucleoside phosphorylase deficiency (PMID: 16139832 , PMID: 32966057 , PMID: 9663253 , +7 More ) Pyruvate carboxylase deficiency Sarcosinemia (PMID: 24341803 , PMID: 17436247 , PMID: 8739971 , +49 More ) Iminoglycinuria (PMID: 19468821 , PMID: 27012787 , PMID: 3168222 , +28 More ) N-acetylglutamate synthetase deficiency (PMID: 4434100 , PMID: 1481808 , PMID: 2044610 , +21 More ) Glucoglycinuria - Concentration is elevated compared to control group (PMID: 4434100 , PMID: 1481808 , PMID: 2044610 , +10 More ) Phenylketonuria - Concentration is elevated compared to control group (PMID: 24023812 , PMID: 6321058 , PMID: 20971021 , +55 More ) Nontypified gene mutations Organic acidemia Succinic semialdehyde dehydrogenase deficiency (PMID: 11978597 , PMID: 12127325 , PMID: 12127325 , +1 More ) Propionic acidemia - Concentration is elevated compared to control group (PMID: 24023812 , PMID: 6321058 , PMID: 20971021 , +65 More ) Maple syrup urine disease - Concentration is elevated compared to control group (PMID: 24023812 , PMID: 6321058 , PMID: 20971021 , +59 More ) Circulatory system disorder Blood and lymphatic system disorder Hyperglycinemia Hypermethioninemia (PMID: 15024124 , PMID: 8745393 , PMID: 27207470 , +6 More ) Leukocytic disorder Leukemia (PMID: 9464484 , PMID: 9464484 , PMID: 27912044 , +25 More ) Metabolic disorder Obesity (PMID: 4434100 , PMID: 1481808 , PMID: 2044610 , +66 More ) Digestive system disorder Gastrointestinal disorder Lower GI Disorder Colorectal cancer (PMID: 25037050 , PMID: 24023812 , PMID: 6321058 , +145 More ) Ulcerative colitis (PMID: 23867873 , PMID: 21761941 , PMID: 25037050 , +78 More ) Upper GI Disorder Eosinophilic esophagitis (PMID: 17334708 , PMID: 32966057 , PMID: 22623390 , +128 More ) Nervous system disorder Central nervous system disorder Alzheimer's disease (PMID: 23857558 , PMID: 22308371 , PMID: 23857558 , +173 More ) Psychiatric disorder (PMID: 11739473 , PMID: 22944140 , PMID: 16959481 , +6 More ) Schizophrenia (PMID: 21359215 , PMID: 22800120 , PMID: 18953024 , +217 More ) Respiratory system disorder Pulmonary disorder Lung cancer (PMID: 24023812 , PMID: 6321058 , PMID: 20971021 , +53 More )

Disposition: Biological location The physiological origin within an organism, including anatomical compnents, biofluids and excreta Cellular substructure:Extracellular Organelle:Lysosome, Peroxisome Non-excretory biofluid:Bile,Blood,Saliva, Excreta:Feces,Sweat,Urine Organ:Bladder,Brain,Intestine,Kidney,Pancreas,Placenta,Prostate,Spleen,Thyroid gland Tissue:Epithelium,Epidermis Cell:Neuron,Hematocyte,Platelet

Source Fruits,Vegetables,Aquatic foods,Herbs and spices,Cereals and cereal products,

Associated disorders diseases: 605899 (D-Glyceric acidemia) 606904 (Juvenile myoclonic epilepsy) 104300 (Alzheimer's disease) 210200 (3-Methyl-crotonyl-glycinuria) 268900 (Sarcosinemia) 608300 (N-acetylglutamate synthetase deficiency) 235800 (Histidinemia) 601665 (Obesity) 256520 (Neu-Laxova Syndrome 1) 614462 (Hyperglycinemia, lactic acidosis, and seizures) 610090 (Pyridoxamine 5-prime-phosphate oxidase deficiency) 616299 (Lipoyltransferase 1 Deficiency) 610992 (Phosphoserine Aminotransferase Deficiency) 614023 (Phosphoserine Phosphatase Deficiency) 181500 (Schizophrenia) 601815 (3-Phosphoglycerate dehydrogenase deficiency) 617290 (Epilepsy, early-onset, vitamin B6-dependent) 114500 (Colorectal cancer) 209850 (Autism) 266600 (Crohn's disease) 138900 (Gout) 260350 (Pancreatic cancer) 170650 (Periodontal disease) 600274 (Frontotemporal dementia) 211980 (Lung Cancer) 237300 (Carbamoyl Phosphate Synthetase Deficiency) 242600 (Iminoglycinuria) 601313 (Autosomal dominant polycystic kidney disease) 207900 (Argininosuccinic aciduria) 606054 (Propionic acidemia) 276700 (Tyrosinemia I) 261600 (Phenylketonuria) 248600 (Maple syrup urine disease) 610247 (Eosinophilic esophagitis) 138070 (Glucoglycinuria)

KEGG compound ID: C00037

CPD link: https://www.genome.jp/dbget-bin/www_bget?cpd:C00037

Process: Alanine metabolism This reversible reaction involves the interconversion of alanine and pyruvate, coupled to the interconversion of alpha-ketoglutarate (2-oxoglutarate) and glutamate. because transamination reactions are readily reversible and pyruvate is widespread, alanine can be easily formed in most tissues Ammonia recycling Arginine and proline metabolism Bile acid biosynthesis Carnitine synthesis Glutamate metabolism Glutathione metabolism Glycine and serine metabolism Methionine metabolism Porphyrin metabolism Purine metabolism

HMDB link: https://hmdb.ca/metabolites/HMDB0000123