ArticleThe Journal of physiology2004
Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- GAMT Deficiency: Clinical Presentation, Treatment, Diagnosis, Animal Models, Preclinical and Clinical Developments.International journal of molecular sciences · 2025Review
- Metabolic Origin, Role and Fate of the Denaturant Guanidine.Microbial biotechnology · 2025Article
- Homoarginine and creatine deficiency do not exacerbate murine ischaemic heart failure.ESC heart failure · 2023Article
- Article
- Effects of Delivering Guanidinoacetic Acid or Its Prodrug to the Neural Tissue: Possible Relevance for Creatine Transporter Deficiency.Brain sciences · 2022Article
- Review
- Role of Creatine in the Heart: Health and Disease.Nutrients · 2021Review
- Arginine:Glycine Amidinotransferase Is Essential for Creatine Supply in Mice During Chronic Hypoxia.Frontiers in physiology · 2021Article
- Article
- Creatine, guanidinoacetate and homoarginine in statin-induced myopathy.Amino acids · 2020Article
- Serum GAA as a Possible Biomarker of Exhaustive Exercise?Frontiers in physiology · 2019Article
- Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine.Cardiovascular research · 2018Article
- A Mouse Model of Creatine Transporter Deficiency Reveals Impaired Motor Function and Muscle Energy Metabolism.Frontiers in physiology · 2018Article
- Advanced physiological roles of guanidinoacetic acid.European journal of nutrition · 2015Review
- Cellular bioenergetics of guanidinoacetic acid: the role of mitochondria.Journal of bioenergetics and biomembranes · 2015Review
- The extended, dynamic mitochondrial reticulum in skeletal muscle and the creatine kinase (CK)/phosphocreatine (PCr) shuttle are working hand in hand for optimal energy provision.Journal of muscle research and cell motility · 2015Article
- Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation.Acta physiologica (Oxford, England) · 2015Review
- X-linked creatine transporter deficiency: clinical aspects and pathophysiology.Journal of inherited metabolic disease · 2014Review
- The location of energetic compartments affects energetic communication in cardiomyocytes.Frontiers in physiology · 2014Article
- Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT-/- mouse hearts.American journal of physiology. Heart and circulatory physiology · 2013Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effects of creatine (Cr) absence in skeletal muscle caused by a deletion of guanidinoacetate methyltransferase (GAMT) were studied in a knockout mouse model by in vivo (31)P magnetic resonance (MR) spectroscopy. (31)P MR spectra of hindleg muscle of GAMT-deficient (GAMT-/-) mice showed no phosphocreatine (PCr) signal and instead showed the signal for phosphorylated guanidinoacetate (PGua), the immediate precursor of Cr, which is not normally present. Tissue pH did not differ between wild-type (WT) and GAMT-/- mice, while relative inorganic phosphate (P(i)) levels were increased in the latter. During ischaemia, PGua was metabolically active in GAMT-/- mice and decreased at a rate comparable to the decrease of PCr in WT mice. However, the recovery rate of PGua in GAMT-/- mice after ischaemia was reduced compared to PCr in WT mice. Saturation transfer measurements revealed no detectable flux from PGua to gamma-ATP, indicating severely reduced enzyme kinetics. Supplementation of Cr resulted in a rapid increase in PCr signal intensity until only this resonance was visible, along with a reduction in relative P(i) values. However, the PGua recovery rate after ischaemia did not change. Our results show that despite the absence of Cr, GAMT-/- mice can cope with mild ischaemic stress by using PGua for high energy phosphoryl transfer. The reduced affinity of creatine kinase (CK) for (P)Gua only becomes apparent during recovery from ischaemia. It is argued that absence of Cr causes the higher relative P(i) concentration also observed in animals lacking muscle CK, indicating an important role of the CK system in P(i) homeostasis.
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