TAILIEUCHUNG - Báo cáo khoa học: Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells Soumen Bera1, Theo Wallimann2, Subhankar Ray1 and Manju Ray1

The creatine⁄creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymesl-arginine:glycine amidinotransferase andN-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carci-noma and Sarcoma 180 cells, whereas both enzymes were virtually unde-tectable in normal muscle. | ỊFEBS Journal Enzymes of creatine biosynthesis arginine and methionine metabolism in normal and malignant cells Soumen Bera1 Theo Wallimann2 Subhankar Ray1 and Manju Ray1 1 Department of BiologicalChemistry Indian Association for the Cultivation of Science Jadavpur Kolkata India 2 Institute of CellBiology ETH Zurich Switzerland Keywords arginine creatine methionine normal muscle sarcoma Correspondence M. Ray Department of Biological Chemistry Indian Association for the Cultivation of Science Jadavpur Kolkata 700 032 India Fax 91 33 2473 2805 Tel 91 33 2473 4971 E-mail bcmr@ Received 19 August 2008 revised 24 September 2008 accepted 30 September 2008 doi The creatine creatine kinase system decreases drastically in sarcoma. In the present study an investigation of catalytic activities western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymes L-arginine glycine amidinotransferase and N-guanidinoacetate methyltransferase in sarcoma Ehrlich ascites carcinoma and Sarcoma 180 cells whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals these enzymes remained unaffected in the kidney or liver of sarcoma-bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells these cells could significantly take up and release creatine suggesting a functional creatine transport as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II ornithine-decarboxylase S-adenosyl-homo-cysteine hydrolase and methionine-synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180

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