Disease relevance of Guanidoacetic acid

• We conclude that in gyrate atrophy patients, formation of guanidinoacetate, creatine, and possibly phosphocreatine is inhibited at the transaminidation step by the high concentrations of ornithine [1].
• Creatine substitution combined with a guanidinoacetate-lowering diet introduced first at the age of 26 years was shown to be effective by an impressive improvement of epileptic seizures, mental capabilities, and general behavior and by normalization of the (31)P spectrum in the skeletal muscle [2].
• The authors describe an Italian child with guanidinoacetate methyltransferase deficiency, neurologic regression, movement disorders, and epilepsy during the first year of life [3].
• The decreased levels of plasma guanidinoacetic acid seen at end-stage renal disease in homozygous and oldest heterozygous rats were also observed in serum of patients with a glomerular filtration rate below 20 ml/min/1.73 m(2) [4].
• Although uric acid, inorganic phosphate, creatinine, potassium, guanidinoacetic acid, and methylguanidine are intracellular substances, they accumulated also in the extracellular fluid in renal failure, and were removed from both compartments, intracellular as well as extracellular, by hemofiltration [5].

Psychiatry related information on Guanidoacetic acid

• Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine [6].

High impact information on Guanidoacetic acid

• Arginine:glycine amidinotransferase (AGAT) catalyzes the first step of creatine synthesis, resulting in the formation of guanidinoacetate, which is a substrate for creatine formation [7].
• In two children with an accumulation of guanidinoacetate in brain and a deficiency of creatine in blood, a severe deficiency of guanidinoacetate methyltransferase (GAMT) activity was detected in the liver [8].
• Interestingly, Rmt2 has 27% sequence identity over 138 amino acids to the mammalian guanidinoacetate N-methyltransferase, an enzyme responsible for methylating the delta-nitrogen of the small molecule guanidinoacetate [9].
• The Km values of D134E for AdoMet and those for guanidinoacetate were increased about 160- and 80-fold over the respective values of wild type [10].
• Prenatal diagnosis of guanidinoacetate methyltransferase deficiency: increased guanidinoacetate concentrations in amniotic fluid [11].

Chemical compound and disease context of Guanidoacetic acid

• Dietary eritadenine suppresses guanidinoacetic Acid-induced hyperhomocysteinemia in rats [12].
• Each of creatinine (Cr), guanidinoacetic acid (GAA) and arginine (Arg) was administered intraperitoneally to rats with renal failure, and the levels of methylguanidine (MG) in the serum, liver, kidney, muscle and urine were determined at certain intervals [13].
• Study on impaired metabolism of guanidinoacetic acid in chronic renal failure rabbits with special reference to impaired conversion of arginine to guanidinoacetic acid [14].

Biological context of Guanidoacetic acid

• The catalytic site of the AoaB adenylation domain provided two aspartate residues, instead of the usual one, which may be involved in the binding of the guanidino moiety of guanidino acetate [15].
• Glycocyamine kinase (GK) catalyzes the reversible phosphorylation of glycocyamine (guanidinoacetate), a reaction central to cellular energy homeostasis in certain animals [16].
• The methylation of guanidinoacetate to form creatine consumes more methyl groups than all other methylation reactions combined [17].
• We also studied the kinetics of the inhibition of Na(+), K(+)-ATPase activity caused by guanidinoacetate [18].
• Evolution of phosphagen kinase VII. Isolation of glycocyamine kinase from the polychaete Neanthes diversicolor and the cDNA-derived amino acid sequences of alpha and beta chains [19].

Anatomical context of Guanidoacetic acid

• In addition, guanidinoacetate, the intermediate of creatine synthesis, is released by astrocytes and may be used for creatine synthesis by other cells, i.e., neurons [20].
• Methylguanidine and guanidinoacetic acid enhanced the lipopolysaccharide (LPS)-stimulated intracellular production of TNF-alpha by normal human monocytes (P < 0.05) [21].
• Levels of arginine as well as its metabolite, guanidinoacetic acid, were increased in the cerebral cortex [22].
• These results suggest that the source of Cr in the male reproductive tract varies depending on the tissue; in the testes and epididymides, Cr is synthesized from guanidinoacetate, while in the seminal vesicles, Cr is transported from blood [23].
• The first enzyme of creatine biosynthesis, L-arginine:glycine amidinotransferase, occurs in the kidney and produces guanidinoacetate, which is released into the renal vein [24].

Associations of Guanidoacetic acid with other chemical compounds

• Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase [25].
• Using a specific HPLC analysis for guanidines, we find that rat aorta contains guanidino succinate (GS), guanidino acetate (GA), guanidino propionate (GP), guanidino butyrate (GB), methyl guanidine (MG) and guanidine [26].
• Native guanidinoacetate methyltransferase binds guanidinoacetate in the presence of sinefungin [27].
• Cerebral (1)H MR spectroscopy showing elevation of brain guanidinoacetate in argininosuccinate lyase deficiency [28].
• Levels of creatinine, guanidinoethanesulfonic acid, creatinine, guanidinoacetic acid and methylguanidine in animal brain were changed at pre- and during convulsions induced by pentylentetrazol, amygdala kindling, iron-induced epileptogenesis and so on [29].

Gene context of Guanidoacetic acid

• GAMT knockout mice have markedly increased guanidinoacetate (GAA) and reduced creatine and creatinine levels in brain, serum and urine, which are key findings in human GAMT patients [30].
• Measurement of guanidinoacetate in body fluids may discriminate GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration) [31].
• A new automated method for the assay of guanidinoacetic acid (GAA) in dried blood spot (DBS) on filter paper is reported [32].
• The activity of kidney L-arginine:glycine amidinotransferase, the enzyme catalyzing the synthesis of guanidinoacetate, was significantly decreased in both supplementation groups [17].
• The aim of this work was to investigate the effect of guanidinoacetate (GAA), the principal metabolite accumulating in guanidinoacetate methyltransferase (GAMT)-deficiency, on Na(+), K(+)-ATPase, Mg(2+)-ATPase and acetylcholinesterase (AChE) activities in striatum of young rats [18].

Analytical, diagnostic and therapeutic context of Guanidoacetic acid

• Creatine and guanidinoacetate concentrations tended to be higher in hemodialysis patients and lower in the undialyzed group of patients with chronic renal failure [33].
• HPLC assay for guanidinoacetate methyltransferase [34].
• In the present study, we investigated regional changes in MG and GAA in (1) AM-kindled rat brain 3 months after completion of kindling and (2) hippocampal (HIPP)-kindled rat brain 7 and 28 days after completion of kindling, using high-performance liquid chromatography [35].
• Stable isotope dilution method for the determination of guanidinoacetic acid by gas chromatography/mass spectrometry [36].
• Multiple sequence alignments of Urechis LK with the only other LK sequence available and CK, AK and glycocyamine kinase sequences, confirm the importance of the small flexible loop located in the N-terminal domain of phosphagen kinases as one component of the structural determinants of guanidine specificity [37].

References