S-Adenosylmethionine (AdoMet) is a metabolically activated form of methionine capable of donating a methyl group. AdoMet is formed in the reaction shown here. Transfer of a methyl group from AdoMet to a target molecule converts AdoMet to S-Adenosylhomocysteine (AdoHcy) (see here). Table 21.1 lists some important AdoMet-dependent transmethylations. Substrates range from small metabolites, such as norepinephrine, to polymers, such as DNA (see here), RNA, or proteins.

In proteins, targets for methylation include lysine, arginine, and residues containing free carboxyl groups. Histones (chromatin proteins), for example, become methylated at specific arginine and lysine residues at particular times in the cell cycle (see here). -N-Trimethyllysine, which is derived specifically from the hydrolysis of methylated proteins, is a precursor of carnitine, which transports fatty acyl moieties across membranes (see here).

Protein methylation plays a role in chemotaxis - the process whereby bacteria sense a chemical concentration gradient in the medium and move either toward or away from it. Methylation may protect proteins by

1. Blocking sites of ubiquitination (ubiquitination is a signal for protein turnover - see here), and

2. Repairing aspartate residues modified by environmental damage.

Except for a few reactions in bacteria, the only known methyl group transfer in cells that does not involve AdoMet is the synthesis of methionine itself. This can happen in two ways:

1. Through the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The methyl group is then transferred to yield methionine via methyl-B12 and methionine synthase (Figure 20.17).

2. Through the oxidation of choline, to yield glycine betaine, followed by the transmethylation of homocysteine shown here.

AdoMet is also a precursor to the plant hormone, ethylene. A similar mechanism is probably involved in making rare fatty acids containing a cyclopropane ring.