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Role of S-adenosylmethionine cycle in carcinogenesis. Murín Radovan,Vidomanová Eva,Kowtharapu Bhavani S,Hatok Jozef,Dobrota Dušan General physiology and biophysics Alterations in enzymatic activities underlying the cellular capacity to maintain functional S-adenosylmethionine (SAM) cycle are associated with modified levels of its constituents. Since SAM is the most prominent donor of methyl group for sustaining the methylation pattern of macromolecules by methyltransferases, its availability is an essential prerequisite for sustaining the methylation pattern of nucleic acids and proteins. In addition, increased intracellular concentrations of S-adenosylhomocysteine and homocysteine, another two constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity of methyltranferases. While methylation pattern of DNA and histones is considered as an important regulatory hallmark in epigenetically regulated gene expression, amended methylation of several cellular proteins, including transcription factors, affects their activity and stability. Indeed, varied DNA methylome is a common consequence of disturbed SAM cycle and is linked with molecular changes underlying the transformation of the cells that may underlay the carcinogenesis. Here we summarize the recent evidences about the impact of disturbed SAM cycle on carcinogenesis. 10.4149/gpb_2017031
Low S-adenosylmethionine/ S-adenosylhomocysteine Ratio in Urine is Associated with Chronic Kidney Disease. Kruglova Maria Petrovna,Grachev Sergej Vital'evich,Bulgakova Polina Olegovna,Ivanov Alexander Vladimirovich,Virus Edward Danielevich,Nikiforova Ksenya Alexandrovna,Fedoseev Anatolij Nikolaevich,Savina Galina Dmitrievna,Kubatiev Aslan Amirkhanovich Laboratory medicine OBJECTIVE:To evaluate the association of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in urine with chronic kidney disease (CKD). METHODS:Case-control study including 50 patients with CKD and 20 healthy volunteers. RESULTS:SAM level and SAM/SAH ratio in urine were significantly lower in patients than in control individuals (P <.001 and P = .01, respectively). The estimated glomerular filtration rate was associated with the SAM level (P = .04) and the SAM/SAH ratio in urine (P = .01). CONCLUSION:CKD is associated not only with the decline in the SAM level but also with the decrease in the SAM/SAH ratio in urine. Thus, use of the urinary SAM/SAH ratio as a noninvasive diagnostic indicator of renal function seems promising. 10.1093/labmed/lmz035