5-Adenosylmethionine, from function

Adenosine triphosphate, coupled reactions and. 1128-1129 function of, 157, 1127-1128 reaction with glucose, 1129 structure of, 157, 1044 S-Adenosylmethionine, from methionine, 669 function of, 382-383 stereochemistry of, 315 structure of, 1045 Adipic acid, structure of, 753 ADP, sec Adenosine diphosphate Adrenaline, biosynthesis of, 382-383 molecular model of, 323 slructure of, 24... 

Although the list of transmethylation reactions in which S-adenosylmethionine can function as the methyl donor could now undoubtedly be greatly expanded, the more recently added reactions, with the exception of the carbon methylations discussed below (Section II,C,6), appear from the chemical point of view to be further examples of types of reactions which were already known. Therefore, no complete compilation will be attempted. From the physiological standpoint, on the other hand, some of the reactions recently studied may be of great interest. For example, systems have now been reported for the enzymic methylation of RNA (Srinavasan and Borek, 1964 Rodeh et al, 1967), DNA (Oda and Marmur, 1966 Kalousek and Morris, 1969), pectin (Kauss and Hassid, 1967), and protein (Comb et al, 1966 Paik and Kim, 1968 Liss et al, 1969). The specific modifications of the properties of these biopolymers consequent to methylation may, of course, be important in... 

Included among drugs that alter the permeability of the membrane are phosphatidylserine, S-adenosylmethionine, and ganglioside extracts. Phosphatidylserine, produced from purified extracts of bovine brain cortex, alters the permeability and functionality of the neuronal membrane. A study... 

Figure 11.6. Schematic diagram of the possible sites of action of drugs that modify dopaminergic function in striatal and other non-mesocortical regions of the mammalian brain. PCM=protein 0-methyltransferase, which catalyses the transfer of methyl groups from S-adenosylmethionine to the calmodulin-dependent regulatory protein and may regulate calcium-calmodulin dependent transmitter synthesis and release. (—)=inhibition (+)=stimulation DA=dopamine. Sites of action of drugs are underlined.

Highly populated protein domain families of H. pylori include (1) the cellular component Helicobacter outer membrane protein family (2) the sell family, which is associated with P-lactamase activity (3) members of the CagA and VacA protein families, which are secreted into host cells and are involved in pathogenesis (4) the ABC transporter family, which is associated with ATP-dependent transport of molecules across the membrane (5) the DNA methyltransferase protein domain family (6) the radical SAM (S-adenosylmethionine) family associated with various metabolic functions of pathogens and (7) the response regulator receiver domain family, which is involved in receiving the signal from the sensor domain in bacterial two-component systems. 

Methylation is the addition of a carbon atom to a molecule, usually causing a change in the function of the methylated molecule. For example, methylation of the neurotransmitter dopamine by catechol-O-methyltransferase renders it inactive. With only two exceptions, 5-adenosylmethionine (SAM), an activated form of the essential amino acid methionine, is the methyl donor for each of the more than 150 methylation reactions, which regulate a large number of cellular functions. One exception is methylation of homocysteine (HCY) to methionine by the cobalamin (vitamin Bi2)-dependent enzyme methionine synthase, which utilizes 5-methyltetrahydrofolate (methylfolate) as the methyl donor, serving to complete the methionine cycle of methylation, as illustrated in Fig. 1 (lower right). Notably, HCY formation from S-adenosylhomocysteine (SAH) is reversible and, as a result, any decrease in methionine synthase activity will be reflected as an increase in both HCY and SAH. This is significant because SAH interferes with SAM-dependent methylation reactions, and a decrease in methionine synthase activity will decrease all of these reactions. Clearly methionine synthase exerts a powerful influence over cell function via its control over methylation. 

Many intracellular proteins can be modified after their biosynthesis by the enzymatic addition of a methyl group from S-adenosylmethionine. These posttransla-tional reactions can permanently or temporarily modify the structure and function of the target proteins. Importantly, these modifications can expand the repertoire of the cellular chemistry performed by proteins. Unmodified proteins must function with only the 20 amino acid residues incorporated in ribosomal protein synthesis, while methylation reactions can create a variety of new types of residues for specialized cellular roles. At this point, we understand best the processes that reversibly form methyl esters at carboxylic acid residues. One such reaction in bacteria methylates glutamate residues on several membrane-bound chemorecep-tors whose signaling properties are modulated by the degree of modification at multiple methylation sites. Another methylation system in higher cells leads to C-terminal methyl ester formation on a variety of proteins such as the small and... 

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