Aminoglycine

Aminoglycine (N-Aminoglycine / Hydrazinoacetic Acid): A Scientific Reference Article

Important Prefatory Note on Scope and Evidence

"Aminoglycine" is occasionally encountered as a chemical synonym or informal name in reagent catalogs and chemistry databases. Exhaustive searching of peer-reviewed literature (PubMed/PMC), government health databases (NIH Office of Dietary Supplements, NCCIH, WHO, EFSA, EMA), pharmacopeial monographs, and evidence-based supplement databases (Examine.com) returns no entries for aminoglycine as a recognized dietary supplement, nutraceutical ingredient, or natural health product. No monographs, clinical trials, dosing guidelines, or traditional-use records for aminoglycine as a supplement exist in these authoritative sources. Any article presenting aminoglycine as an established dietary supplement with documented health benefits, traditional uses, clinical dosing, or safety profiles would necessarily contain fabricated information not supported by verifiable sources. This article instead provides a thorough, fully sourced account of what aminoglycine actually is according to the available scientific record.

Identity and Chemical Characterization

Names and Registry Information

Aminoglycine is a chemical synonym for hydrazinoacetic acid (HAA), also known as N-aminoglycine. Additional synonyms recorded in chemical databases include 2-hydrazinylacetic acid, 2-diazanylethanoic acid, hydrazino acetic acid, and hydrazinylacetic acid; it is registered under CAS number 14150-64-2 and EINECS number 237-995-8.

The molecular formula is C₂H₆N₂O₂ with a molecular weight of 90.082 g/mol; its SMILES notation is N(N)CC(=O)O, indicating the connectivity of the hydrazine group to the acetic acid backbone.

Physical and Chemical Properties

2-Hydrazinylacetic acid is an organic compound characterized by the presence of both hydrazine and acetic acid functional groups; it typically appears as a white to off-white crystalline solid and is soluble in water due to its polar nature.

The compound features a hydrazine (–NH–NH₂) moiety attached to an acetic acid (–COOH) group, which contributes to its reactivity and potential applications in various chemical syntheses.

Structural Relationship to Glycine

Hydrazinoacetic acid (HAA) is a non-proteinogenic amino acid analogue in which the α-amino group of glycine is replaced by a hydrazine moiety. Glycine itself (2-aminoacetic acid, NH₂–CH₂–COOH) carries a primary amine at the alpha carbon; in aminoglycine, that amine is replaced by a hydrazinyl group (–NH–NH₂), making aminoglycine structurally distinct from glycine and incapable of being incorporated into proteins by the standard ribosomal machinery.

Natural Occurrence and Biosynthetic Context

Aminoglycine/hydrazinoacetic acid is not a standard proteinogenic amino acid and is not found as a free nutrient in common foods. Historically identified in the mid-20th century as a synthetic antimetabolite, HAA gained prominence for its potent inhibition of the Glycine Cleavage System (GCS) and pyridoxal phosphate (PLP)-dependent enzymes. While early literature focused on its utility as a chemical probe for glycine metabolism, recent genomic studies have re-identified HAA as a transient, "hidden" intermediate in the biosynthesis of complex natural products like Triacsins and Azaserine in Streptomyces species.

Didomain proteins called hydrazine synthetases (Spb40 homologs), consisting of zinc-binding cupin and methionyl-tRNA synthetase (MetRS)-like domains, are widely distributed in genome databases and synthesize various hydrazinoacetic acid (HAA) derivatives in microbial biosynthetic pathways.

Research published in Applied and Environmental Microbiology identifies a Streptomyces noursei biosynthetic gene cluster that produces a nitramine natural product, N-nitroglycine, via the formation of a hydrazine precursor, establishing hydrazinoacetic acid as a biosynthetic precursor of bacterially produced nitramines.

Several studies have identified enzymes responsible for N–N bond formation involving HAA intermediates; Spb40 and its homologs have been reported to synthesize a hydrazine moiety from N⁶-hydroxylysine and amino acids such as glycine and glutamate, with N–N bond formation catalyzed by the didomain protein Spb40 composed of an N-terminal cupin domain and a C-terminal MetRS-like domain.

These natural occurrences are exclusively within microbial (primarily Streptomyces) secondary metabolite pathways. Aminoglycine is not a plant-derived botanical ingredient, not a mammalian metabolite under normal physiological conditions, and is not present in the human diet at detectable or nutritionally meaningful levels according to any reviewed source.

Historical and Traditional Use

No traditional or historical medicinal uses of aminoglycine (hydrazinoacetic acid) have been recorded in any of the authoritative sources searched, including WHO monographs, ESCOP, German Commission E records, Ayurvedic or Traditional Chinese Medicine pharmacopeias, or ethnobotanical literature. Historically identified in the mid-20th century as a synthetic antimetabolite, HAA gained prominence as a research tool for its potent inhibition of the Glycine Cleavage System and pyridoxal phosphate-dependent enzymes, a role that is confined entirely to laboratory biochemical research rather than traditional healing practices.

Studies on the central nervous effects of hydrazinoacetic acid and its derivatives were published in the German pharmacological literature as early as 1964 (Ackermann E, Oehme P, Rex H, Lange P. Acta Biol Med Ger. 1964;12:322–41), representing early experimental pharmacological investigation rather than traditional therapeutic use. These mid-20th century studies were conducted in experimental contexts, not as part of any recognized clinical or traditional medicine tradition.

Key Constituents and Mechanisms of Action

Mechanism-Based Inhibition of PLP-Dependent Enzymes

The core mechanism of action of HAA in cellular models is defined by carbonyl trapping. HAA acts as a mechanism-based inhibitor of pyridoxal 5'-phosphate (PLP)-dependent enzymes, particularly aminotransferases.

PLP-dependent enzymes are central to amino acid metabolism across all domains of life. The hydrazine group of aminoglycine forms a stable covalent hydrazone adduct with the aldehyde moiety of PLP at the enzyme active site, trapping the cofactor and preventing its catalytic function. This is the same general mechanism exploited by several clinically studied hydrazine-containing drugs, such as isoniazid (used in tuberculosis treatment), but aminoglycine itself has not been developed or approved for any therapeutic indication.

Inhibition of the Glycine Cleavage System

The glycine cleavage system (GCS) has four components: a P protein containing a PLP-dependent glycine decarboxylase; H protein with a lipoic acid-containing hydrogen carrier; T protein which is tetrahydrofolate-dependent; and L protein which is the lipoamide dehydrogenase moiety also known as E3 of the pyruvate dehydrogenase complex.

Because aminoglycine mimics glycine structurally while carrying a hydrazine group instead of an amine, it competes with glycine for binding to the P protein of the GCS and forms an irreversible adduct with the active-site PLP, thereby blocking glycine catabolism. HAA gained prominence for its potent inhibition of the Glycine Cleavage System (GCS) and pyridoxal phosphate (PLP)-dependent enzymes, making it a useful biochemical probe but also raising substantial toxicological concerns (see Safety section).

Structural Peptidomimetic Applications

In drug development contexts, HAA serves as a critical pharmacophore for peptidomimetics. A versatile synthesis of Boc-protected hydrazinoacetic acid and its application to the chemoselective ligation of TASP molecules was described by Banfi D, Mutter M, and Patiny L (Protein Pept Lett. 2004 Dec;11(6):539–42); this paper describes the synthesis of protected hydrazine derivatives, specifically 1,2-bis-Boc-hydrazinoacetic acid, and its application for hydrazone ligation techniques in convergent template assembled synthetic protein (TASP) synthesis.

2-Hydrazinylacetic acid is known for its role as a building block in the synthesis of more complex molecules, particularly in medicinal chemistry and biochemistry, and it can participate in various chemical reactions, including condensation and coupling reactions, making it valuable in the development of pharmaceuticals and agrochemicals.

Scientific Evidence by Area of Potential Activity

There are no published human clinical trials or systematic reviews evaluating aminoglycine (hydrazinoacetic acid) as a dietary supplement or therapeutic agent in humans. The following sections summarize the only verifiable body of scientific evidence, which is restricted to biochemical, in vitro, and early experimental pharmacological research.

Glycine Metabolism and the Glycine Cleavage System

Aminoglycine's most thoroughly characterized biochemical activity is inhibition of the GCS. The GCS is the primary pathway for glycine catabolism in humans. The GCS comprises a multienzyme system present in a wide range of organisms and is the major pathway for the catabolism of glycine in humans. Blocking this pathway with aminoglycine or structurally related inhibitors causes intracellular glycine accumulation. This mechanism is of scientific interest because dysregulation of the GCS underlies the inherited metabolic disorder nonketotic hyperglycinemia (NKH). Mutations in the gene that encodes GLDC (glycine decarboxylase), or, less commonly, mutations in genes encoding AMT or GCSH, underlie the inherited metabolic disorder non-ketotic hyperglycinemia (NKH); NKH, also known as glycine encephalopathy, is characterized by accumulation of glycine in tissues and body fluids such as plasma and cerebrospinal fluid, and results in a range of neurodevelopmental defects.

Evidence quality: Biochemical and genetic; no human interventional data for aminoglycine itself.

Oncology Research Context (GCS Inhibition)

Separately from aminoglycine specifically, the GCS pathway that aminoglycine inhibits has been studied in oncology contexts because certain cancer cell lines show elevated reliance on glycine catabolism. Inhibition of a GCS component (glycine cleavage system protein H, GCSH) or treatment with cysteamine, a small molecule known inhibitor of the GCS, markedly impaired viability of cell lines in the GLDC-knockdown-sensitive group; multiple lines of evidence indicate that inhibition of the GCS reduces the viability of tumor cells of a variety of different tumor types. However, aminoglycine itself has not been evaluated in published oncology clinical trials, and this mechanistic connection does not constitute evidence that aminoglycine is useful or safe as a cancer intervention in humans.

Evidence quality: Preclinical/mechanistic only. No human data for aminoglycine.

Neurological Research Context (GCS Inhibition and NMDA Signaling)

Methods for treating psychotic disorders, including schizophrenia, major depression, manic-depressive disorder, Alzheimer's disease, and post-traumatic stress syndrome, through administration of inhibitors of the glycine cleavage system have been proposed in the patent literature, based on the premise that increasing brain glycine concentrations can augment NMDA receptor-mediated neurotransmission. Administering the glycine cleavage system inhibitor was proposed as affecting augmentation of NMDA receptor-mediated neurotransmission. These concepts remain at the level of mechanistic hypotheses and patent filings; they were not developed into human clinical trials specifically evaluating aminoglycine.

Evidence quality: Mechanistic hypothesis; patent literature only. No human clinical data for aminoglycine.

Peptide Chemistry and Drug Discovery Research

2-Hydrazinylacetic acid is known for its role as a building block in the synthesis of more complex molecules, particularly in medicinal chemistry and biochemistry. In this context, aminoglycine is a laboratory reagent rather than an active ingredient. Its structural incorporation into peptidomimetic scaffolds — exploiting the hydrazine moiety's reactivity — is a tool for basic research and drug discovery, not a supplementation strategy.

Evidence quality: Applied chemistry research only. No clinical evidence.

Body Systems and Health Areas Nominally Associated with Aminoglycine

The following body systems are mentioned solely in the context of the biochemical mechanisms described above. No therapeutic evidence in humans exists for aminoglycine in any of these areas.

• Central Nervous System: Via inhibition of the GCS, aminoglycine could theoretically alter brain glycine levels, which modulate NMDA receptor activity. Early experimental pharmacological studies from the 1960s (Ackermann et al., 1964) examined central nervous effects in animal models.
• Amino Acid and One-Carbon Metabolism: The GCS, which aminoglycine inhibits, is central to glycine catabolism and the generation of one-carbon units (via 5,10-methylenetetrahydrofolate) required for nucleotide biosynthesis and methylation reactions.
• Oncological Research: Glycine catabolism through the GCS has been implicated in supporting proliferation of certain cancer cell types, making GCS inhibitors of scientific interest in basic oncology research.

Dosage Forms and Reported Dosages

No dosage forms or dosing regimens for aminoglycine (hydrazinoacetic acid) as a dietary supplement exist in any authoritative source. Aminoglycine is available from chemical suppliers at a stated purity of 95%, with a molecular weight of 90.082 g/mol, and is designated for storage at 2–8°C, indicating its status as a laboratory reagent requiring cold storage — not a standard supplement formulation. It is not listed in any pharmacopeia, not recognized by the FDA as a dietary supplement ingredient with established use, and is not reviewed by the European Food Safety Authority (EFSA) or other food/supplement regulatory bodies in a health context.

Safety Considerations

Safety information for aminoglycine as a dietary supplement does not exist because it has not been evaluated as a supplement. The following safety considerations are drawn from its established biochemical pharmacology.

Hydrazine Moiety Toxicity

2-Hydrazinylacetic acid can participate in various chemical reactions, including condensation and coupling reactions; due to the presence of the hydrazine group, it may exhibit biological activity, which warrants careful handling due to potential toxicity. The hydrazine functional group is a well-characterized toxicophore in medicinal chemistry. Hydrazine and hydrazine derivatives are associated with hepatotoxicity, neurotoxicity, and carcinogenic potential in experimental animal studies; this is the mechanistic basis for the toxicity of some hydrazine-containing drugs such as isoniazid and procarbazine.

Mechanism-Based Enzyme Inhibition

The core mechanism of action of HAA is carbonyl trapping; HAA acts as a mechanism-based inhibitor of pyridoxal 5'-phosphate (PLP)-dependent enzymes, particularly aminotransferases. PLP-dependent enzymes are involved in a wide range of essential metabolic processes including transamination, decarboxylation, and the catabolism of many amino acids. Broad inhibition of these enzymes would be expected to have systemic metabolic consequences, potentially including interference with neurotransmitter synthesis (e.g., GABA, serotonin, and dopamine biosynthesis all involve PLP-dependent steps) and disruption of sulfur amino acid metabolism.

GCS Inhibition and Glycine Accumulation

Pathological accumulation of glycine, as seen in the genetic disorder NKH, causes severe neurological symptoms. NKH, also known as glycine encephalopathy, is characterized by accumulation of glycine in tissues and body fluids such as plasma and cerebrospinal fluid, and results in a range of neurodevelopmental defects. Pharmacological inhibition of the GCS by agents such as aminoglycine could theoretically produce a similar state of hyperglycinemia.

Absence of Human Safety Data

No controlled human studies, no GRAS (Generally Recognized As Safe) designation by the U.S. FDA, no EFSA opinion, and no WHO safety evaluation for aminoglycine as an ingested agent have been located in any authoritative source. Its use as a chemical research reagent requires specialized laboratory handling conditions (cold storage, appropriate personal protective equipment) consistent with the recognized hazards of hydrazine derivatives.

Regulatory and Classification Status

Aminoglycine (hydrazinoacetic acid) is not listed in the FDA's Dietary Supplement Ingredient Advisory List, the NIH Office of Dietary Supplements ingredient databases, the EFSA nutrition and novel food databases, or any pharmacopeial compendium reviewed (USP, European Pharmacopoeia, British Pharmacopoeia). It is commercially available exclusively as a chemical reagent for laboratory research and synthesis purposes. No national or international regulatory agency has evaluated it as a food ingredient, dietary supplement, or over-the-counter health product.

Disambiguation: Aminoglycine vs. Related Terms

The following terms are sometimes confused with "aminoglycine" and should be clearly distinguished:

• Glycine (2-aminoacetic acid): A well-characterized, proteinogenic amino acid with an extensive human clinical research record including studies in schizophrenia, sleep quality, metabolic health, and collagen synthesis. Glycine is the parent structure from which aminoglycine differs by substitution of the amino group with a hydrazine group. Glycine is a recognized dietary supplement ingredient.
• Aminoglycosides: A completely unrelated class of antibiotic drugs (e.g., gentamicin, streptomycin, tobramycin, amikacin). The term aminoglycoside is derived from the chemical structure of these compounds, which are made up of amino groups (–NH₂) attached to glycosides (derivatives of sugar). Aminoglycosides are prescription antimicrobial agents, not dietary supplements, and have no chemical relationship to aminoglycine/hydrazinoacetic acid.
• N-aminoglycine: A direct synonym for aminoglycine/hydrazinoacetic acid as described in this article.

Summary of Evidence Status

Aminoglycine (N-aminoglycine; hydrazinoacetic acid; CAS 14150-64-2) is a non-proteinogenic amino acid analogue of glycine in which the alpha-amino group is replaced by a hydrazine moiety. It occurs naturally as a biosynthetic intermediate in certain bacterial (Streptomyces) natural product pathways and has been studied as a biochemical research tool — specifically as a mechanism-based inhibitor of PLP-dependent enzymes and the glycine cleavage system. There is no credible evidence base supporting its use as a dietary supplement in humans. No clinical trials, traditional use records, pharmacopeial monographs, regulatory approvals, or institutional health-body reviews of aminoglycine as a supplement or health ingredient exist in any source reviewed. Its inherent chemical properties — specifically the reactive hydrazine group and potent enzyme-inhibitory activity — present theoretical safety concerns that further preclude any evidence-based recommendation for human supplemental use.

References

• BenchChem: Hydrazinoacetic acid (CAS 14150-64-2) — Technical Review
• ChemSpider: Hydrazinoacetic acid (C2H6N2O2) — Chemical Structure and Synonyms
• CymitQuimica: CAS 14150-64-2 — 2-Hydrazinylacetic acid
• BOC Sciences: CAS 14150-64-2 Hydrazinoacetic acid — Literature References
• Applied and Environmental Microbiology: Hydrazinoacetic acid is a biosynthetic precursor of N-nitroglycine
• PMC: In vitro characterization of NRPS-dependent O-(2-hydrazineylideneacetyl)serine synthesis in azaserine biosynthesis
• PMC: Identification of a l-Threonine-Utilizing Hydrazine Synthetase for Thrazarine Biosynthesis in Streptomyces coerulescens
• PMC: Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria
• USPTO Patent 9,493,775: Inhibition of the glycine cleavage system for treatment of cancer
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• ChemShuttle: Aminoglycine CAS 14150-64-2 — Reagent Catalog Entry