Letters To The Editor
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2017; 23(40): 7343-7346
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7343
S-Adenosyl-L-methionine towards hepatitis C virus expression: Need to consider S-Adenosyl-L-methionine’s chemistry, physiology and pharmacokinetics
Dimitrios Tsikas, Erik Hanff, Alexander Bollenbach
Dimitrios Tsikas, Erik Hanff, Alexander Bollenbach, Core Unit Proteomics, Hannover Medical School, Hannover 30623, Germany
Author contributions: Tsikas D, Hanff E and Bollenbach A wrote and revised the manuscript.
Conflict-of-interest statement: All listed authors in this manuscript do not have financial relationships to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dimitrios Tsikas, Professor, Core Unit Proteomics, Centre of Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany. tsikas.dimitros@mh-hannover.de
Telephone: +49-511-5323984
Received: August 21, 2017
Peer-review started: August 22, 2017
First decision: September 21, 2017
Revised: September 25, 2017
Accepted: October 17, 2017
Article in press: October 17, 2017
Published online: October 28, 2017
Processing time: 68 Days and 14.6 Hours
Abstract

S-Adenosyl-L-methionine (SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus -expressing cells at millimolar concentrations. The efficacy of SAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated.

Keywords: S-Adenosyl-L-methionine; Bioavailability; Concentration; Liver

Core tip:S-Adenosyl-L-methionine (SAM) serves as a cofactor for enzymes that transfer its methyl group to nucleophilic functionalities of various biomolecules including DNA and RNA. Exogenous SAM has been shown to be a useful pharmacological agent in liver-associated diseases. SAM is a labile species, undergoes spontaneous decomposition in biological samples, and its oral bioavailability is only about 2%. Lozano-Sepulveda and colleagues observed that SAM modulates antioxidant enzymes, restores glutathione synthesis, and switches MAT1/MAT2 turnover in hepatitis C virus (HCV) expressing cells. The authors suggested that this may be a likely mechanism by which HCV expression is diminished by SAM. This SAM concentration range was chosen on the basis of cell viability experiments and is up to 1000 times higher than physiological intracellular. Other groups have used SAM in the concentration range 0 - 1000 nmol/L. The efficacy of SAM, its pharmacological effects towards HCV and possibly adverse effects beyond cell viability need to be elaborated in further studies using SAM concentrations much lower than 1 mmol/L.