Guanidinoacetate methyltransferase activity in tissues and cultured cells

Daly, Marie M.

doi:10.1016/0003-9861(85)90661-7

Cited by 40 publications

(34 citation statements)

References 15 publications

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“…The kidney and pancreas are assumed to be the principal organs for GAA synthesis through the action of AGAT, and is itself the immediate precursor of Cr. The final methylation step to Cr is performed by GAMT and was assumed (with the exception of brain) to occur primarily in the liver, although other sites including muscle (Daly 1985) have been suggested based on GAMT localization. In papers reviewed by Ostojic (2016), oral administration of GAA was effective in raising the muscle TCr pool, which because of its greater stability in aqueous and mildly acidic conditions makes it an attractive alternative to Cr in sport-related products.…”

Section: Creatine In Sportmentioning

confidence: 99%

Creatine: a miserable life without it

Wallimann

Harris

2016

Amino Acids

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Section: Creatine In Sportmentioning

confidence: 99%

Creatine: a miserable life without it

Wallimann

Harris

2016

Amino Acids

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“…Cr is synthesized in the mammalian brain (Pisano et al 1963;Van Pilsum et al 1972), in nerve cell lines as well as in primary and organotypic brain cell cultures (Daly 1985;Dringen et al 1998;Braissant et al 2002). AGAT and GAMT are expressed in CNS, where they are found in all the main structures of the brain, in every main cell types (neurons, astrocytes and oligodendrocytes, Fig.…”

Section: Agat Gamt and Slc6a8 In Cnsmentioning

confidence: 99%

Creatine deficiency syndromes and the importance of creatine synthesis in the brain

et al. 2011

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Creatine deficiency syndromes, due to deficiencies in AGAT, GAMT (creatine synthesis pathway) or SLC6A8 (creatine transporter), lead to complete absence or very strong decrease of creatine in CNS as measured by magnetic resonance spectroscopy. Brain is the main organ affected in creatine-deficient patients, who show severe neurodevelopmental delay and present neurological symptoms in early infancy. AGAT-and GAMT-deficient patients can be treated by oral creatine supplementation which improves their neurological status, while this treatment is inefficient on SLC6A8-deficient patients. While it has long been thought that most, if not all, of brain creatine was of peripheral origin, the past years have brought evidence that creatine can cross blood-brain barrier, however, only with poor efficiency, and that CNS must ensure parts of its creatine needs by its own endogenous synthesis. Moreover, we showed very recently that in many brain structures, including cortex and basal ganglia, AGAT and GAMT, while found in every brain cell types, are not coexpressed but are rather expressed in a dissociated way. This suggests that to allow creatine synthesis in these structures, guanidinoacetate must be transported from AGAT-to GAMT-expressing cells, most probably through SLC6A8. This new understanding of creatine metabolism and transport in CNS will not only allow a better comprehension of brain consequences of creatine deficiency syndromes, but will also contribute to better decipher creatine roles in CNS, not only in energy as ATP regeneration and buffering, but also in its recently suggested functions as neurotransmitter or osmolyte.

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“…Low activity is reported in skeletal and cardiac muscle, mouse neuroblastoma cells, and human fetal lung Wbroblasts [2]. The discovery of the Wrst case of GAMT deWciency [3], and more recently of other patients with the same enzymatic defect, has drawn attention to the analytical procedures used to measure the activity of this enzyme in human cells with low expression so as to avoid the more invasive hepatic biopsy.…”

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confidence: 98%

“…The discovery of the Wrst case of GAMT deWciency [3], and more recently of other patients with the same enzymatic defect, has drawn attention to the analytical procedures used to measure the activity of this enzyme in human cells with low expression so as to avoid the more invasive hepatic biopsy. Previously published assays for GAMT activity [2,4,5] used radiolabeled molecules as substrates to reach high sensitivity and speciWcity. Moreover, all of these methods consist of numerous steps (e.g., extraction, puriWcation of the extracts, quantiWcation), require high amounts of cells, and show high unspeciWc blank radioactivity and, therefore, are more useful for detecting GAMT in tissues than in cells with low activity [2].…”

mentioning

confidence: 99%

“…Previously published assays for GAMT activity [2,4,5] used radiolabeled molecules as substrates to reach high sensitivity and speciWcity. Moreover, all of these methods consist of numerous steps (e.g., extraction, puriWcation of the extracts, quantiWcation), require high amounts of cells, and show high unspeciWc blank radioactivity and, therefore, are more useful for detecting GAMT in tissues than in cells with low activity [2]. Ilas et al [6] developed a speciWc and sensitive method to measure GAMT activity in human-cultured Wbroblasts, Epstein-Barr virus-transformed lymphoblasts, and cultivated amniotic cells but still with radiolabeled substrate.…”

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confidence: 99%

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