Metabolism of S-adenosylhomocysteine and S-tubercidinylhomocysteine in neuroblastoma cells

Abstract

The metabolism of the methylase product inhibitor S-adenosylhomocysteine and its 7-deaza analogue S-tubercidinylhomocysteine has been studied in cultured N-18 neuroblastoma cells. The latter compound, designed to resist metabolic degradation, has been shown to be inert under the same conditions where S-adenosylhomocysteine is rapidly and extensively degraded. The product analyses elucidated by high-performance liquid chromatography indicate that the primary route of S-[8-(14)C]adenosylhomocysteine metabolism in these cells leads to adenosine. This product does not accumulate but is rapidly converted to nucleotides or oxypurines by the action of adenosine kinase and adenosine deaminase, respectively. The presence of the potent adenosine deaminase inhibitor coformycin leads to a pronounced inhibition of oxypurine formation, an increase in nucleotide formation, and a slight accumulation of the primary metabolic products adenosine and adenine.

S-Adenosyl-L-methionine-dependent macromolecule methyltransferases: potential targets for the design of chemotherapeutic agents

“…Recently, the importance of this enzyme in the metabolism of AdoHcy has been verified in vivo using rat and mouse brain, kidney, and liver homogenates130-132 and neuroblastoma cells. 133 These studies have shown that the major metabolic pathway for AdoHcy in these mammalian tissues is the cleavage of the homocysteine-ribose bond (via AdoHcy hydrolase) with subsequent metabolism of adenosine to nucleotides or oxypurines.…”

Effect of undermethylation on mRNA cytoplasmic appearance and half-life.

“…STH is a competitive inhibitor of mRNA methyltransferases due to its structural similarity to S-adenosylhomocysteine. Previous studies have indicated that STH is stable in cells (9) because it is not a substrate for S-adenosylhomocysteine hydrolase (6). Treatment of cells with STH results in subtle changes, if * Corresponding author.…”

Diterpenoid sweeteners. Synthesis and sensory evaluation of stevioside analogs nondegradable to steviol

“…0 Pw = compound potency calculated on a weight basis;Pm = compound potency calculated on a molar basis. yield after ion exchange9 and recrystallization from methanol: mp10a 183-186 °C; IR10b 2.90 (OH), 5.86 (0=0), 6.04 (C=CH2), 8.55 (S=0), 9.30 (S=0) pm; NMR10c 0.82 (s, 3 H, 20-CHa), 1.13 (s, 3 H, I8-CH3), 4.75 (s, 1 H, 17-CH), 4.88 (s, 1 H, 17-CH). Neutralization equivalents:106 caled, 787; found, 791.…”