Distinct Tissue-Specific Gene Expression Reveals Different Creatine-Synthesizing Pathways Between Mammals and Fish

Creatine and its phosphorylated form are important metabolites as they act as a cellular energy buffer. In mammals, creatine synthesis and usage are spatially separated. The first step of creatine synthesis catalyzed by GATM (glycine amidinotransferase) mainly takes place in the kidney, whereas the second step catalyzed by GAMT (guanidinoacetate N-methyltransferase) is predominantly performed in the liver. Creatine is then transported to its targets, which are mainly tissues with high energy-demand like brain or muscle where it is used by creatine kinases (CKs). Recently, we could show that the spatial separation of creatine synthesis and usage is not present in rainbow trout, as muscle expresses high levels of GATM and GAMT. In this study, we examined further piscine species (herring, perch, pike-perch, whitefish) as well as three mammals (mouse, cow, pig) concerning their creatine system. We identified new partial cDNA sequences of piscine GATM, GAMT and CKM using degenerated primers. Quantitative Real-Time PCR determined the gene expressions. Overall, the results in other fishes confirmed the findings in rainbow trout. Muscular expression of GATM and GAMT were very strong in piscine muscle in comparison to liver and kidney. This indicates that muscular creatine synthesis may be a key concept of piscine energy provision. In addition to that, we could show a diverse gene expression of GATM in mammals, as hepatic GATM expression exceeded the renal expression in cow and pig in contrast to mice, highlighting the importance of comparative examinations. ESF Grant AU11040.