Premium Nahrungsergänzungsmittel | artgerecht

AGAT – Arginine-Glycine-Amidinotransferase Explained

AGAT (Arginine-Glycine-Amidinotransferase) is an enzyme that plays a key role in creatine biosynthesis. An AGAT deficiency can lead to a rare inherited metabolic disorder.

Regular tips about health Regular tips about health

Things worth knowing about "AGAT"

AGAT (Arginine-Glycine-Amidinotransferase) is an enzyme that plays a key role in creatine biosynthesis. An AGAT deficiency can lead to a rare inherited metabolic disorder.

What is AGAT?

AGAT stands for Arginine-Glycine-Amidinotransferase, an enzyme found primarily in the kidneys and liver. It catalyzes the first step of creatine biosynthesis in the human body: the transfer of an amidino group from arginine to glycine, producing guanidinoacetate (also called guanidinoacetic acid) and ornithine. Creatine is a vital molecule essential for energy supply to muscles and the brain.

Biological Function

AGAT plays a central role in creatine metabolism. The compound guanidinoacetate produced by AGAT is subsequently converted to creatine in the liver by the enzyme Guanidinoacetate Methyltransferase (GAMT). Creatine is then transported into muscles and the brain via the creatine transporter (SLC6A8), where it serves as a short-term energy reservoir.

Catalyzes the first step of creatine synthesis
Produces guanidinoacetate as an intermediate product
Primarily active in the kidneys and pancreas
Regulated by creatine itself through negative feedback

AGAT Deficiency: Causes

AGAT deficiency (also known as creatine deficiency syndrome type 1 or AGAT deficiency) is a rare, autosomal recessively inherited metabolic disorder. It is caused by mutations in the GATM gene, located on chromosome 15, which encodes the AGAT enzyme. The condition leads to reduced or absent creatine synthesis in the body.

Symptoms of AGAT Deficiency

Since creatine is essential for brain energy metabolism, AGAT deficiency primarily manifests through neurological symptoms:

Intellectual disability (cognitive developmental delay)
Speech and language delay
Muscle hypotonia (reduced muscle tone)
Behavioral abnormalities (e.g., autistic features)
Epilepsy (seizures in some affected individuals)
Growth retardation

Diagnosis

The diagnosis of AGAT deficiency involves several diagnostic steps:

Urine analysis: Decreased guanidinoacetate levels in urine (in contrast to GAMT deficiency, where guanidinoacetate is elevated)
Blood test: Reduced creatine levels in plasma
Magnetic Resonance Imaging (MRI): Reduced creatine signal in the brain, detectable by Magnetic Resonance Spectroscopy (MRS)
Genetic testing: Identification of mutations in the GATM gene to confirm the diagnosis
Enzyme activity assay: Measurement of AGAT activity in fibroblasts or other tissues

Treatment

Treatment of AGAT deficiency is very promising, particularly when initiated early. Unlike many other metabolic disorders, AGAT deficiency responds well to therapy:

Creatine supplementation: Oral administration of creatine monohydrate can compensate for the creatine deficiency in the body and brain. When started early (ideally in infancy), neurological symptoms can largely be prevented.
Dosage: Dosage is based on body weight and is individually determined by a physician.
Early diagnosis: Newborn screening for creatine deficiency syndromes is being discussed in several countries, as early treatment can prevent severe neurological damage.

AGAT in the Context of Other Creatine Deficiency Syndromes

AGAT deficiency belongs to the group of Creatine Deficiency Syndromes (CDS), which also includes GAMT deficiency and creatine transporter deficiency (SLC6A8 deficiency). All three disorders result in cerebral creatine deficiency but differ in their causes, biomarkers, and treatment options. AGAT deficiency is the rarest of the three forms.

References

Schulze A. - Creatine deficiency syndromes. In: Saudubray JM et al. (eds.): Inborn Metabolic Diseases. Springer, Berlin, 2016.
Item CB et al. - Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. American Journal of Human Genetics, 2001; 69(5): 1127-1133.
Stockler-Ipsiroglu S et al. - Guanidinoacetate methyltransferase (GAMT) deficiency and arginine:glycine amidinotransferase (AGAT) deficiency: a systematic review of literature to understand the phenotypic spectrum. Orphanet Journal of Rare Diseases, 2015; 10: 20.

Building Blocks for a Healthy Life

As an integrated manufacturer, we develop & produce evidence-based, patented, and non-patented formulations. We work exclusively with plant and natural extracts according to the strictest purity & quality standards.
The combination of science & modern technology with the laws of nature creates solutions consistently tailored to humans – for the highest good: health.