S-ADENOSYLMETHIONINE AND METHYLATION

S-Adenosylmethionine (AdoMet or SAM) plays a pivotal role as a methyl donor in a myriad of biological and biochemical events, Although it ha s been claimed that AdoMet itself has therapeutic benefits, it remains to be established whether it can be taken up intact by cells, S-Adeno sylhomocysteine (AdoHcy), formed after donation of the methyl group of AdoMet to a methyl acceptor, is then hydrolyzed to adenosine and homo cysteine by AdoHey hydrolase. This enzyme has long been a target for i nhibition as its blockade can affect methylation of phospholipids, pro teins, DNA, RNA, and other small molecules, Protein carboxymethylation may he involved in repair functions of aging proteins, and heat shock proteins are methylated in response to stress. Bacterial chemotaxis i nvolves carboxymethylation and demethylation in receptor-transducer pr oteins, although a similar role in mammalian cells is unclear. The pre cise role of phospholipid methylation remains open, DNA methylation is related to mammalian gene activities, somatic inheritance, and cellul ar differentiation. Activation of some genes has been ascribed to the demethylation of critical mCpG loci, and silencing of some genes may b e related to the methylation of specific CpG loci, Viral DNA genomes e xist in cells as extrachromosomal units and are generally not methylat ed, although once integrated into host chromosomes, different patterns of methylation are correlated with altered paradigms of transcription al activity, Some viral latency may be related to DNA methylation, Cel lular factors have been found to interact with methylated DNA sequence s, Methylation of mammalian ribosomal RNAs occurs soon after the synth esis of its 47S precursor RNA in the nucleolus before cleavage to smal ler fragments. Inhibition of the methylation of rRNA affects its proce ssing to mature 18S and 28S rRNAs, The methylation of 5'-terminal cap plays an important role in mRNA export from the nucleus, efficient tra nslation, and protection of the integrity of mRNAs, Another important function of AdoMet is that it serves as the sole donor of an aminoprop yl group that is conjugated with putrescine to form, first, the polyam ine spermidine, and then spermine.