Enzymes of creatine biosynthesis, arginine and methioninemetabolism in normal and malignant cells

Abstract: The creatine ⁄ creatine kinase system decreases drastically in sarcoma. In thepresent study, an investigation of catalytic activities, western blot andmRNA expression unambiguously demonstrates the prominent expressionof the creatine-synthesizing enzymes l-arginine:glycine amidinotransferaseand N-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carci-noma and Sarcoma 180 cells, whereas both enzymes were virtually unde-tectable in normal muscle. Compared to that of normal animals, theseenzymes remained unaffected in the kidney or liver of sarcoma-bearingmice. High activity and expression of mitochondrial arginase II in sarcomaindicated increased ornithine formation. Slightly or moderately higherlevels of ornithine, guanidinoacetate and creatinine were observed in sar-coma compared to muscle. Despite the intrinsically low level of creatine inEhrlich ascites carcinoma and Sarcoma 180 cells, these cells could signifi-cantly take up and release creatine, suggesting a functional creatine trans-port, 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 upregulatedin sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Over-all, the enzymes related to creatine and arginine ⁄ methionine metabolismwere found to be significantly upregulated in malignant cells. However, thelow levels of creatine kinase in the same malignant cells do not appear tobe sufficient for the building up of an effective creatine ⁄ phosphocreatinepool. Instead of supporting creatine biosynthesis, l-arginine:glycine ami-dinotransferase and N-guanidinoacetate methyltransferase appear to begeared to support cancer cell metabolism in the direction of polyamine andmethionine synthesis because both these compounds are in high demand inproliferating cancer cells.

Link to article: https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1742-4658.2008.06718.x

PubMed: https://pubmed.ncbi.nlm.nih.gov/19021765/

Authors: Soumen Bera , Theo Wallimann , Subhankar Ray and Manju Ray

Key Terms: Basic Science, Animal Study, In vitro, General Creatine