Glycocyamine (or guanidinoacetate) is a metabolite of

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

in which the

amino group In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...

has been converted into a

guanidine Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...

by guanylation (transfer of a guanidine group from

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

). In vertebrate organism it is then transformed into

creatine Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...

methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...

. Glycocyamine is used as a supplement and as a

feed additive A feed additive is an additive of extra nutrient or drug for livestock. Such additives include vitamins, amino acids, fatty acids, minerals, pharmaceutical, fungal products and steroidal compounds. The additives might impact feed presentation, hygi ...

poultry farming Poultry farming is the form of animal husbandry which raises domesticated birds such as chickens, ducks, turkeys and geese to produce meat or eggs for food. Poultry – mostly chickens – are farmed in great numbers. More than 60 billion chicke ...

. However, the metabolism of creatine from glycocyamine in the liver causes a depletion of

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

s. This causes

homocysteine Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In the b ...

levels to rise, which has been shown to produce cardiovascular and skeletal problems. Glycocyamine plays a role in the metabolism of the amino acids

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

and

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

Production

Biochemical synthesis

Glycocyamine is formed in the mammalian organism primarily in the

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

by transferring the guanidine group of L-arginine by the enzyme L-Arg:Gly-amidinotransferase (AGAT) to the amino acid glycine. From L-arginine,

ornithine Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl. Role in urea cycle L-Ornithine is one of the produ ...

is thus produced, which is metabolized in the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts highl ...

by carbamoylation to

citrulline The organic compound citrulline is an α-amino acid. Its name is derived from ''citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in 1 ...

In a further step, glycocyamine is methylated to creatine with ''S''-adenosyl methionine by the enzyme

guanidinoacetate N-methyltransferase Guanidinoacetate N-methyltransferase () is an enzyme that catalyzes the chemical reaction and is encoded by gene ''GAMT'' located on chromosome 19p13.3. :S-adenosyl-L-methionine + guanidinoacetate \rightleftharpoons S-adenosyl-L-homocysteine + ...

(GAMT). The creatine is released into the

bloodstream The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

Chemical synthesis

Guanidinoacetic acid was first prepared in 1861 by

Adolph Strecker Adolph Strecker (October 21, 1822 – November 7, 1871) was a German chemist who is remembered primarily for his work with amino acids. Life and work Strecker was born in Darmstadt, the son of Friedrich Ludwig Strecker, an archivist working for ...

by reaction of

cyanamide Cyanamide is an organic compound with the chemical formula, formula carbon, Cnitrogen, N2hydrogen, H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcoho ...

with

in aqueous solution: GAA from cyanamide + glycine

Glycine can also be converted to glycocyamine with ''S''-methylisothiourea or with ''O''-alkylisoureas as a guanylation agent. GAA via S-Meisothiourea

The recent patent literature describes the synthesis of glycocyamine by catalytic oxidation of

ethanolamine Ethanolamine (2-aminoethanol, monoethanolamine, ETA, or MEA) is an organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorless, viscous liquid wit ...

to glycine and subsequent reaction with cyanamide in aqueous solution in high yield, analogous to the synthesis of

starting from

2-methylaminoethanol ''N''-Methylethanolamine is an alkanolamine with the formula CH3NHCH2CH2OH. It is flammable, corrosive, colorless, viscous liquid.Matthias Frauenkron, Johann-Peter Melder, Günther Ruider, Roland Rossbacher, Hartmut Höke "Ethanolamines and Pro ...

via

sarcosine Sarcosine, also known as ''N''-methylglycine, or monomethylglycine, is a monopeptide with the formula CH3N(H)CH2CO2H. It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2−, which can be obtained as a white, water-soluble powder. Like some ...

This synthetic route suppresses the formation of toxic dihydrotriazine and other undesired by-products (such as

iminodiacetic acid Iminodiacetic acid is the organic compound with the formula HN(CH2CO2H)2, often abbreviated to IDA. A white solid, the compound is a dicarboxylic acid amine (the nitrogen atom forms a secondary amino group, not an imino group as the name suggests ...

Properties

Industrially produced guanidinoacetic acid is sold as a white (to yellowish) fine powder, which is granulated for improve handling, metering and uptake with starch into aggregates with a mean diameter of 200-400 microns. The granulate provides a long-term stability of glycocyamine. The shelf Life of guanidinoacetate in acidic aqueous solution is significantly higher than that of creatine, which cyclizes to

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...

under acid catalysis.

Uses

As a supplement

A series of studies showed that a combination of

betaine A betaine () in chemistry is any neutral chemical compound with a positively charged cationic functional group, such as a quaternary ammonium or phosphonium cation (generally: onium ions) that bears no hydrogen atom and with a negatively charge ...

and glycocyamine improves the symptoms of patients with chronic illness, including heart disease, without

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

. Betaine can provide a

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

group to glycocyamine, via

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

, for the formation of creatine. In overall, such treatment led to less fatigue, greater strength and endurance, and an improved sense of well-being. The patients with cardiac decompensation (

arteriosclerosis Arteriosclerosis is the thickening, hardening, and loss of elasticity of the walls of Artery, arteries. This process gradually restricts the blood flow to one's organs and tissues and can lead to severe health risks brought on by atherosclerosis ...

rheumatic disease Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including art ...

) and congestive

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

had improved cardiac function. The patients gained weight (improved

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

balance) and saw lessened symptoms of

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

and

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

and increased

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...

, and those people suffering from

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

experienced transient reduced

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

. Also the studies shows the increase of glucose tolerance in both diabetic subjects and subjects without diabetes.

As a feed additive

Guanidinoacetic acid is a nutritional

approved by

the European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

for chickens for fattening, weaned piglets and pigs for fattening. It is supposed to lead with a "vegetarian diet" (meaning without feeding of animal protein) to higher feed conversion, higher weight gain and improved muscle increase already at a low dosage (600 g/to feed). Possible benefits of glycocyamine supplementation can not yet be conclusively assessed, neither in other breeding, fattening and domestic animals nor for high-performance athletes, analogous to the glycocyamine metabolite creatine. The simultaneous intake of methyl providing substances such as

appears advisable because of the risk of

formation with glycocyamine alone.S.M. Ostojic et al., ''Co-administration of methyl donors along with guanidinoacetic acid reduces the incidence of hyperhomocysteinaemia compared with guanidinoacetic acid administration alone'', Br. J. Nutr. (2013), Jan 28:1-6