Archives

Guanidinoacetic acid (GAA) accumulates in the genetic deficiency of the GAMT enzyme and it is believed to cause the seizures that often occur in this condition. However, evidence that it is indeed epileptogenic is scarce and we previously found that it does not cause neuronal hyperexcitation in in vitro brain slices. Here, we used Micro-Electrode […]

GAA induces epileptogenesis and neurotoxicity in the brain. As epileptic animal models have been reported to show elevated cerebral GAA levels, the processing mechanism of GAA in the brain is important for maintaining brain homeostasis. We have revealed that GAA in the cerebrospinal fluid (CSF) is removed by incorporation into the choroid plexus epithelial cells […]

The enzymes AGAT and GAMT function together to synthesize creatine from arginine, glycine, and S-Adenosyl methionine. Deficiency in either enzyme or the creatine transporter, CT1, results in a devastating neurological disorder, Cerebral Creatine Deficiency Syndrome (CCDS). To better understand the pathophysiology of CCDS, we mapped the distribution of GATM and GAMT at single cell resolution, […]

Guanidinoacetate (GAA), which is a precursor of creatine, is mainly biosynthesized in the renal proximal tubular epithelial cells (RPTECs). Plasma concentration of GAA has been reported to be reduced in patients with monocarboxylate transporter 12 (MCT12) mutation (p.Q215X). However, the mechanism underlying GAA release from the RPTECs remains unclear. Therefore, to elucidate the role of […]

Although protein synthesis dominates the requirements for dietary amino acids, the need for amino acids to meet demand for synthesis of other compounds is not negligible. This is especially true of production of creatine, which requires substantial amounts of arginine and methionine. Synthesis of guanidino acetate (GAA), the precursor for creatine, constitutes the main pathway […]

Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, […]

Arginine:glycine amidinotransferase, necessary for the conversion of arginine (Arg) to guanidinoacetic acid (GAA), is expressed mainly in kidney and pancreas. The methylation of GAA to creatine (Cre) primarily occurs in the liver. The role of the gut in Cre homeostasis has not been characterized. We aimed to quantify the contribution of kidney, pancreas, and gut […]

Guanidinoacetic acid (GAA) is a fundamental intermediate in cellular bioenergetics, with circulating levels of GAA often reflects disturbances in its conversion due to many intrinsic and extrinsic factors, including gender or age. Here, we evaluated serum GAA in 172 healthy women aged 18 to 65 years, with age found to significantly predict serum GAA concentrations […]

Elevated serum creatine and higher handgrip strength are individually associated with better health profiles yet the link between two variables remains unknown. In this cross-sectional study, we evaluated serum creatine levels in relation to handgrip strength in a cohort of 130 young healthy adults (61 women and 69 men; age 23.3 ± 2.6 years), while […]

Guanidinoacetate (GAA) is a biosynthetic precursor of creatine, which plays a critical role in homeostasis of high-energy phosphates in the brain, but cerebral accumulation of GAA leads to neurological complications, such as epilepsy and seizures. The purpose of the present study was to clarify the contribution of the γ-aminobutyric acid (GABA) transport systems to GAA […]