Date of Award
Doctor of Philosophy
John T. Smith
Jane R. Savage, Dileep S. Sachan, Robert H. Feinbert
Regulation of transmethylation by lowering the molar ratio of S-adenosylmethionine to S-sdenosylhomocysteine (SAM: SAH ration) was studied. Reduction of the ration in vitro caused a decrease in the activities of rat liver thiopurine methyltransferase (TPMT), thiol methyl-transferase (TMT), and protien(lysine)methyltransferase (PLMT). Furthermore, rats injected with D,L-homocysteine thiolactone had a reduction in the hepatic SAM:SAH ration, as well as a decrease in the activities of TPMT and PLMT, but not TMT, in liver.
Reduction of the hepatic SAM:SAH ratio in rats fed a pyridoxine-deficient diet resulted in a decrease in the activity of PLMT, but not TPMT and TMT, in liver. Moreover, the levels of total acid-soluble carnitine (ASCNE) were lowered in skeletal muscle and heart of these rats, but palmitate oxidation in vitro was not impared in either tissue. On the other hand, the rate of palmitate oxidation in skeletal muscle decreased in rats subjected to an apparent feed restriction, despite normal levels of tissue ASCNE and elevated cytochrome oxidase activity.
Phospholipid methylation was impaired during pyridoxine deficiency, above and beyond that seen during feed restriction. A reduction in the hepatic microsomal level of phosphatidylcholine and an elevation of phosphatidylethanolamine was found, incongruous with an increase in the activity of phosphatidylethanolamine metyltransferase.
Pyridoxine-deficient rats displayed no significant change in the activity of guanidoacetate methyltransferase in liver, but a decrease in arginine-glycine transamidinase activity of the kidney. The concentrations of creatine in liver and skeletal muscle of these animals increased, once again above and beyond that observed in feed-restricted rats alone. No change in urinary creatinine excretion was demonstrated.
The data indicate that under certain conditions, the SAM:SAH ratio may regulate some biochemical processes related to transmethylation. Cellular compartmentalization and nutritional state may perhaps determine if control is possible in vivo.
Loo, George, "Modulation of the S-Adenosylmethionine to S-Adensoyhomocyseine Ratio: Effect on Transmethylation. " PhD diss., University of Tennessee, 1986.