The AtlasAmino acidsNonpolar, aliphatic
GlycineGly · G
The smallest amino acid, with a single hydrogen for a side chain: every third residue of collagen, the first atoms of haem, and an inhibitory transmitter in the spinal cord.
Molecule · Gly · 5 heavy atoms
Glycine
C2H5NO275.07 g/mol
The smallest amino acid, with a single hydrogen for a side chain: every third residue of collagen, the first atoms of haem, and an inhibitory transmitter in the spinal cord.
Built fromthe charted ones open their own entry
- Codes
- Gly · G
- Formula
- C2H5NO2
- Molar mass
- 75.07 g/mol
- Systematic name
- 2-aminoacetic acid
- Side chain
- A single hydrogen atom; the smallest and most flexible residue in proteins.
- Class
- Nonpolar, aliphatic
- In the diet
- Conditionally essential
- Carbon skeleton
- Glucogenic
- pKa
- α-COOH 2.34 · α-NH3+ 9.60
- Isoelectric point
- pH 5.97
- Hydropathy
- -0.4 (Kyte–Doolittle)
- Codons
GGUGGCGGAGGG- Main transporters
- SLC6A9 (GlyT1), SLC6A5 (GlyT2)
pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.
In brief
What it is
The simplest amino acid: its side chain is one hydrogen atom, so it is the only one without left- and right-handed forms. The body makes it, mostly from serine 1.
Why it matters
Collagen, the most abundant protein in animals, is built on glycine at every third position 2; haem begins with glycine 3; and glycine is an inhibitory transmitter in the spinal cord and brainstem and a co-agonist of the NMDA receptor in the brain 4,5.
Where it runs short
Glycine is made, but perhaps not in enough: one estimate puts synthesis at about 3 g a day and diet at 1.5 to 3 g, against needs that may be about 10 g a day higher, mostly for collagen 1.
Where it turns
When the glycine cleavage system fails, glycine accumulates in every tissue, especially the brain, and severe nonketotic hyperglycinaemia causes intractable seizures and no developmental progress 6,7.
A molecule with nothing on its side chain turns out to be a structural, signalling and metabolic requirement all at once.
The molecule
Glycine’s side chain is a hydrogen atom. That makes it the smallest residue, and the most flexible: it can take backbone angles no other amino acid can, which is why it turns up in tight turns and at the centre of collagen’s triple helix 2.
Collagen is a right-handed bundle of three left-handed helices 2. Every third position faces the crowded axis where the three chains meet, and only glycine fits there. In osteogenesis imperfecta, substituting another amino acid for one of these glycines in type I collagen weakens bone, and in some stretches of the chain, where collagen binds its partners, the substitution is lethal 8,9.
StereochemistryGlycine has no stereocentre: with hydrogen as its side chain, its α-carbon carries two identical groups, so there is no L- or D-glycine.
Move across the chart to read the charge at any pH.
Computed from its pKa values (α-carboxyl 2.34, α-amino 9.60) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.
Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.
| 1st ↓ 2nd → | U | C | A | G | 3rd |
|---|---|---|---|---|---|
| U | UUUPhe | UCUSer | UAUTyr | UGUCys | U |
| UUCPhe | UCCSer | UACTyr | UGCCys | C | |
| UUALeu | UCASer | UAAStop | UGAStop | A | |
| UUGLeu | UCGSer | UAGStop | UGGTrp | G | |
| C | CUULeu | CCUPro | CAUHis | CGUArg | U |
| CUCLeu | CCCPro | CACHis | CGCArg | C | |
| CUALeu | CCAPro | CAAGln | CGAArg | A | |
| CUGLeu | CCGPro | CAGGln | CGGArg | G | |
| A | AUUIle | ACUThr | AAUAsn | AGUSer | U |
| AUCIle | ACCThr | AACAsn | AGCSer | C | |
| AUAIle | ACAThr | AAALys | AGAArg | A | |
| AUGMet | ACGThr | AAGLys | AGGArg | G | |
| G | GUUVal | GCUAla | GAUAsp | GGUGly | U |
| GUCVal | GCCAla | GACAsp | GGCGly | C | |
| GUAVal | GCAAla | GAAGlu | GGAGly | A | |
| GUGVal | GCGAla | GAGGlu | GGGGly | G |
Where it comes from
The body makes glycine mainly from serine, by serine hydroxymethyltransferase, which also produces a one-carbon unit for folate metabolism. Comparing every reported flux in an adult, synthesis from serine provided more than 85% of glycine, about 3 g a day 1.
The same analysis estimated that synthesis plus 1.5 to 3 g from the diet may fall around 10 g a day short of total use, mostly by collagen, and argued that glycine should count as semi-essential 1. This is a calculation, not a measured deficiency.
Conditionally essentialMade mainly from serine, more than 85% of the total, by serine hydroxymethyltransferase; because that reaction yields only as much glycine as one-carbon units, some authors argue glycine is semi-essential 1,10.
How much
None set; the body makes it, though some argue not in sufficient amounts 1.
In the bottle · syntheticCommercial glycine is mostly made by chemical synthesis; because it has no stereocentre, there is no natural or unnatural form to choose between 12.
What the body does with it
Glycine is a building block for more molecules than its size suggests. The whole glycine molecule goes into creatine, along with parts of arginine and methionine 13. It is the third amino acid of glutathione 14. It supplies the carbons and nitrogen that begin haem 3. And through glycine-acyltransferase it conjugates carboxylic acids such as benzoate, so that they can be excreted 15,16.
In the spinal cord and brainstem glycine is an inhibitory transmitter. Its receptors are chloride channels built from α1 and β subunits, and a presynaptic transporter, GlyT2, recaptures it for reuse; mutations in all three cause hyperekplexia, startle disease 4,17,18.
In the brain glycine also works the other way. In 1987 it was found to potentiate the excitatory NMDA receptor through a site insensitive to strychnine 5; extrasynaptic NMDA receptors use glycine as their co-agonist, while synaptic ones prefer D-serine 19.
In three sentences each
Every third residue of collagen
Collagen is three helices wound into a rope, and only glycine is small enough to sit at the centre where they touch, so the sequence repeats Gly-X-Y; substituting another amino acid for one glycine is a classic cause of osteogenesis imperfecta 2,9.
How it is made, moved and broken down
Glycine is broken down by the mitochondrial glycine cleavage system into CO₂, ammonia and a one-carbon unit carried by folate. When it fails, glycine accumulates; molecular analysis in 124 patients identified 99% of mutant alleles, mostly in the gene for its P-protein 7.
Carbon skeleton · glucogenicConverted to serine and on to pyruvate, or split by the glycine cleavage system into CO₂, ammonia and a one-carbon unit 1,7.
- Serine + THF
- Serine hydroxymethyltransferaseSHMT1, SHMT2 · vitamin B6
- Glycine + 5,10-methylene-THF
- Glycine + THF
- Glycine cleavage systemGLDC, AMT, GCSH · vitamin B6, lipoate, NAD⁺
- CO₂ + NH₃ + 5,10-methylene-THF
- Glycine + succinyl-CoA
- ALA synthaseALAS1, ALAS2 · vitamin B6
- δ-Aminolevulinic acid
- AGAT, then GAMTGATM, GAMT · SAM
- Guanidinoacetate → creatine
Where it matters most
When it goes wrong
Inherited
Nonketotic hyperglycinaemia
GLDC, AMT · autosomal recessive
Glycine accumulates in all tissues, especially the brain. The severe form brings intractable epilepsy and no developmental progress; the attenuated form is variable 6. In 124 patients, brain malformations were common in the severe form, 71%, and rare in the attenuated, 7.5% 7. Treatment with sodium benzoate, to conjugate glycine, and NMDA receptor blockers such as dextromethorphan is not curative 6.
How it is foundPaired CSF and plasma glycine; GLDC and AMT sequencing 7.
Inherited
Hyperekplexia (startle disease)
GLRA1, GLRB, SLC6A5 · dominant or recessive
Newborn stiffness, exaggerated startle and stiffening after the startle, with a risk of apnoea and sudden death; most motor features respond to clonazepam 4,22. GLRA1 and SLC6A5 are the main genes, with GLRB the third 17,18.
How it is foundClinical, including the nose-tap test, and gene panel 22.
Inherited
Osteogenesis imperfecta
COL1A1, COL1A2 and others · mostly dominant
Fragile, deformed bones from defects of type I collagen or the proteins that process it 9. Glycine substitutions in the collagen helix are a major cause, and in some regions are lethal 8.
How it is foundClinical and genetic testing 9.
Drug
Erythropoietic protoporphyria
FECH, ALAS2
Protoporphyrin builds up in red cells and causes painful reactions to sunlight 3. In a phase 2 trial in 75 adults, the GlyT1 inhibitor bitopertin lowered protoporphyrin by 30 to 50% against placebo and reduced phototoxic reactions 21.
How it is foundWhole-blood metal-free protoporphyrin 21.
How it is measured
Glycine is part of the standard plasma, urine and CSF amino acid analysis, by ion-exchange chromatography or mass spectrometry 23. For nonketotic hyperglycinaemia, paired CSF and plasma samples give both the diagnosis and a guide to prognosis 7.
- CSF and plasma glycineMeasured together to diagnose nonketotic hyperglycinaemia, as part of the standard amino acid analysis 7,23.In 124 patients, CSF glycine above 230 µmol/L indicated a severe outcome and a CSF-to-plasma ratio of 0.08 or less predicted the attenuated form 7.Paired samples must be taken at the same time, and valproate raises glycine, which can unmask or mimic the disease 24.
Food, supplements and the evidence
Establishedreplicated in people, for a named outcome
- Sodium benzoate, which removes glycine as hippurate, is part of treatment for nonketotic hyperglycinaemia 6.
Uncertainsmall, short, mixed, surrogate or preclinical
- Glycine, 3 g at bedtime, for sleep quality and next-day fatigue: three small trials, all positive, all from closely related groups 11,25.
- GlyNAC, glycine with N-acetylcysteine, in ageing: one small trial in 24 older adults reported broad improvements 14, while a 114-person trial in healthy older adults found no rise in glutathione, its primary endpoint 26.
- Glycine and lifespan: 4 to 6% longer life in mice 27; no human data.
What is strange about it
A drug that blocks a glycine transporter may treat a disease of sunlight. Erythropoietic protoporphyria has one approved treatment, which does not touch its cause 28; bitopertin, by starving red cell precursors of glycine for haem, cut protoporphyrin by up to half and reduced reactions to sunlight in a 17-week trial 20,21.
In the Interventions Testing Program, which tests drugs and diets in genetically mixed mice, a diet with 8% glycine extended median lifespan by 4 to 6% in both sexes 27. In people, genetic analysis of 80,003 participants supports a protective link between glycine and coronary disease, but suggests the link with diabetes runs the other way, insulin resistance lowering glycine 29.
Glycine for sleep rests on three small trials, a rat study that traced the effect to NMDA receptors in the body-clock region of the brain and a fall in core temperature, and a 2026 scoping review that called the mechanism plausible 11,25,30.
Where it connects
In the Atlas
Topics on the map
On the map
A star in Longevity & NAD, one of 14. Made in the body but not always in enough: shortfalls show up in glutathione, collagen — and in homocysteine.
Sources
30 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.
- 1Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, et al. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.doi:10.1007/s12038-009-0100-9 · PMID 20093739
A flux calculation, not a measured deficiency.
- 2Shoulders MD, Raines RT. Collagen structure and stability.doi:10.1146/annurev.biochem.77.032207.120833 · PMID 19344236
The triple helix.
- 3Di Pierro E, Granata F, De Canio M, et al. Recognized and emerging features of erythropoietic and X-linked protoporphyria.doi:10.3390/diagnostics12010151 · PMID 35054318
ALAS2 joins glycine and succinyl-CoA.
- 4Bode A, Lynch JW. The impact of human hyperekplexia mutations on glycine receptor structure and function.doi:10.1186/1756-6606-7-2 · PMID 24405574
Glycine receptors and startle disease.
- 5Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons.doi:10.1038/325529a0 · PMID 2433595
The discovery of the NMDA co-agonist site.
- 6Nowak M, Chuchra P, Paprocka J. Nonketotic hyperglycinemia: insight into current therapies.doi:10.3390/jcm11113027 · PMID 35683414
Benzoate and NMDA antagonists; no causal treatment.
- 7Swanson MA, Coughlin CR, Scharer GH, et al. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia.doi:10.1002/ana.24485 · PMID 26179960
124 patients; CSF glycine and the ratio as predictors.
- 8Sałacińska K, Pinkier I, Rutkowska L, et al. Novel mutations within collagen alpha1(I) and alpha2(I) ligand-binding sites, broadening the spectrum of osteogenesis imperfecta: current insights into collagen type I lethal regions.doi:10.3389/fgene.2021.692978 · PMID 34306033
Lethal regions of glycine substitution.
- 9Forlino A, Marini JC. Osteogenesis imperfecta.doi:10.1016/S0140-6736(15)00728-X · PMID 26542481
Seminar.
- 10Reeds PJ. Dispensable and indispensable amino acids for humans.doi:10.1093/jn/130.7.1835S · PMID 10867060
Glycine as conditionally indispensable.
- 11Fan Z, Nelson JM, Wallace TC. Glycine bioavailability and sleep-related outcomes following oral glycine and collagen supplementation: a scoping review.doi:10.1080/19390211.2026.2726197 · PMID 42687500
22 trials; three on glycine and sleep.
- 12Leuchtenberger W, Huthmacher K, Drauz K. Biotechnological production of amino acids and derivatives: current status and prospects.doi:10.1007/s00253-005-0155-y · PMID 16195792
Fermentation, enzymatic and chemical routes.
- 13Brosnan JT, da Silva RP, Brosnan ME. The metabolic burden of creatine synthesis.doi:10.1007/s00726-011-0853-y · PMID 21387089
The whole glycine molecule goes into creatine.
- 14Kumar P, Liu C, Suliburk J, et al. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: a randomized clinical trial.doi:10.1093/gerona/glac135 · PMID 35975308
24 older adults; one research group.
- 15Rohwer JM, Schutte C, van der Sluis R. Functional characterisation of three glycine N-acyltransferase variants and the effect on glycine conjugation to benzoyl-CoA.doi:10.3390/ijms22063129 · PMID 33803916
The glycine conjugation pathway.
- 16Nourbakhsh M, Miryounesi M, Tale A, et al. Glycine-acyltransferase deficiency due to a homozygous nonsense variant in the GLYAT: a novel inborn error of metabolism.doi:10.1002/jmd2.70032 · PMID 40747359
First reported case.
- 17Carta E, Chung SK, James VM, et al. Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.doi:10.1074/jbc.M112.372094 · PMID 22700964
SLC6A5 in 17 of 93 index cases.
- 18Chung SK, Bode A, Cushion TD, et al. GLRB is the third major gene of effect in hyperekplexia.doi:10.1093/hmg/dds498 · PMID 23184146
117 gene-negative cases screened.
- 19Papouin T, Ladépêche L, Ruel J, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists.doi:10.1016/j.cell.2012.06.029 · PMID 22863013
D-serine at synapses, glycine outside them. Rodent work.
- 20Ducamp S, Wu M, Putra J, et al. The GLYT1 inhibitor bitopertin mitigates erythroid PPIX production and liver disease in erythroid protoporphyria.doi:10.1172/JCI181875 · PMID 40663422
Preclinical; GlyT1 in erythroid cells.
- 21Yeung AK, Bonkovsky HL, Balwani M, et al. Bitopertin shows efficacy in patients with erythropoietic protoporphyria: results from the randomized, double-blind, placebo-controlled AURORA trial.doi:10.1016/j.jaad.2025.12.024 · PMID 41390126
75 adults, 17 weeks; small and short.
- 22Falsaperla R, Sortino V, Giacchi V, et al. Neonatal hyperekplexia: is it still a diagnostic challenge? Evidence from a systematic review.doi:10.1177/08830738241273425 · PMID 39223854
14 genetically confirmed newborns.
- 23Sharer JD, De Biase I, Matern D, et al. Laboratory analysis of amino acids, 2018 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).doi:10.1038/s41436-018-0328-6 · PMID 30459394
Methods for amino acid analysis.
- 24Subramanian V, Kadiyala P, Hariharan P, et al. A rare case of glycine encephalopathy unveiled by valproate therapy.doi:10.4103/1817-1745.159200 · PMID 26167219
Case report.
- 25Bannai M, Kawai N, Ono K, et al. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers.doi:10.3389/fneur.2012.00061 · PMID 22529837
3 g at bedtime after three nights of restricted sleep.
- 26Lizzo G, Migliavacca E, Lamers D, et al. A randomized controlled clinical trial in healthy older adults to determine efficacy of glycine and N-acetylcysteine supplementation on glutathione redox status and oxidative damage.doi:10.3389/fragi.2022.852569 · PMID 35821844
114 people, two weeks; no rise in glutathione.
- 27Miller RA, Harrison DE, Astle CM, et al. Glycine supplementation extends lifespan of male and female mice.doi:10.1111/acel.12953 · PMID 30916479
Interventions Testing Program; 4–6% longer median life.
- 28Barman-Aksözen J, Granata F, Wäscher S, et al. New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin.doi:10.1080/14656566.2026.2651281 · PMID 41885813
Afamelanotide the only approved treatment.
- 29Wittemans LBL, Lotta LA, Oliver-Williams C, et al. Assessing the causal association of glycine with risk of cardio-metabolic diseases.doi:10.1038/s41467-019-08936-1 · PMID 30837465
80,003 people; Mendelian randomisation.
- 30Kawai N, Sakai N, Okuro M, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus.doi:10.1038/npp.2014.326 · PMID 25533534
Rats.
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