Glycocyamine


Glycocyamine is a metabolite of glycine in which the amino group has been converted into a guanidine by guanylation. In vertebrate organism it is then transformed into creatine by methylation.
Glycocyamine is used as a supplement and as a feed additive in poultry farming. However, the metabolism of creatine from glycocyamine in the liver causes a depletion of methyl groups. This causes homocysteine levels to rise, which has been shown to produce cardiovascular and skeletal problems. Glycocyamine itself is not an amino acid but it plays a role in the metabolism of the amino acids serine, threonine and proline.

Production

Biochemical synthesis

Glycocyamine is formed in the mammalian organism primarily in the kidneys by transferring the guanidine group of L-arginine by the enzyme L-Arg:Gly-amidinotransferase to the amino acid glycine. From L-arginine, ornithine is thus produced, which is metabolized in the urea cycle by carbamoylation to citrulline.
In a further step, glycocyamine is methylated to creatine with S-adenosyl methionine by the enzyme guanidinoacetate N-methyltransferase. The creatine is released into the bloodstream.

Chemical synthesis

Guanidinoacetic acid was first prepared in 1861 by Adolph Strecker by reaction of cyanamide with glycine in aqueous solution:
Glycine can also be converted to glycocyamine with S-methylisothiourea or with O-alkylisoureas as a guanylation agent.
The recent patent literature describes the synthesis of glycocyamine by catalytic oxidation of ethanolamine to glycine and subsequent reaction with cyanamide in aqueous solution in high yield, analogous to the synthesis of creatine starting from 2-methylaminoethanol via sarcosine.
This synthetic route suppresses the formation of toxic dihydrotriazine and other undesired by-products.

Properties

Industrially produced guanidinoacetic acid is sold as a white 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 under acid catalysis.

Uses

As a supplement

A series of studies showed that a combination of betaine and glycocyamine improves the symptoms of patients with chronic illness, including heart disease, without toxicity. Betaine can provide a methyl group to glycocyamine, via methionine, 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 and congestive heart failure had improved cardiac function. The patients gained weight and saw lessened symptoms of arthritis and asthma and increased libido, and those people suffering from hypertension experienced transient reduced blood pressure. 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 feed additive approved by EFSA in poultry farming. It is supposed to lead with a "vegetarian diet" to higher feed conversion, higher weight gain and improved muscle increase already at a low dosage.
Benefits of glycocyamine supplementation in other breeding, fattening and pets, as well as analogous to the glycocyamine metabolite creatine in high-performance athletes can not yet be conclusively assessed. The simultaneous administration of methyl group donors such as betaine appears advisable because of the risk of homocysteine formation when glycocyamine is administered alone.
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 betaine appears advisable because of the risk of homocysteine formation with glycocyamine alone.