Transport ofS-Adenosylmethionine in Isolated Rat Liver Mitochondria

Mitochondria do not have the enzyme, methionine adenosyltransferase (ATP:l-methionineS-adenosyltransferase, EC 2.5.1.6), necessary for the biosynthesis ofS-adenosylmethionine. Nevertheless, about 30% of total hepaticS-adenosylmethionine resides in the mitochondria and radiolabeledS-adenosylmethionine may be isolated from the mitochondria after administration of radiolabeled methionine. This leads to the hypothesis that a carrier-mediated system is responsible forS-adenosylmethionine transport from the cytosol into the mitochondria. We have characterized such a system in isolated rat liver mitochondria. Uptake ofS-adenosylmethionine consisted of two components. One component was incorporation of the methyl group into phospholipids as shown by thin-layer chromatography. The second component represented uptake into the mitochondria since addition of excess unlabeledS-adenosylmethionine resulted in efflux of labeled substrate. This countertransport is characteristic of a carrier-mediated transport system. Uptake (corrected for incorporation into phospholipids) was saturable with an apparentKm= 8.9 μmandVmax= 54.3 pmol·mg protein−1·min−1. Uptake was not inhibited by methionine, adenosine, 5′-methylthioadenosine, carnitine, choline, betaine, quinine, or hemicholinium-3. Uptake was inhibited by sinefungin and byS-adenosylhomocysteine (Ki= 53.4 μm). Uptake ofS-adenosylmethionine was not dependent on the electrical potential across the mitochondrial membrane. These results indicate thatS-adenosylmethionine is taken up into mitochondria via a specific, carrier-mediated system.