Reference

Effect of 5'-methylthioadenosine, 3-deazaadenosine, and related compounds on human natural killer cell activity

Effect of 5'-methylthioadenosine, 3-deazaadenosine, and related compounds on human natural killer cell activity. Relation to cyclic AMP and methylation potential. Fredholm, B. B.; Jondal, M.; Lanefelt, F.; Ng, J. (Dep. Pharmacol., Karolinska Inst., Stockholm 104 01, Swed.). Scand. J. Immunol., 20(6), 511-18 (English) 1984. CODEN: SJIMAX. ISSN: 0300-9475. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 15 The effect of 5'-methylthioadenosine (MTA) [2457-80-9] on human lymphocyte natural killer (NK) cell activity was examd. and compared with the effect of 3-deazaadenosine (c3-ado) [6736-58-9] and periodate-oxidized adenosine (ado-ox) [29847-35-6]. MTA inhibited NK cell activity in concns. >30 mM, but in concns. <10 mM, a slight enhancing effect was often obsd. C3-ado and ado-ox were 10 and 3 times more potent, resp. as inhibitory agents and did not increase NK cell activity in low concns. The inhibitory effect of c3-ado was unaffected by preincubation of the cells but was enhanced by the addn. of L-homocysteine. In concns. that caused inhibition of NK cell activity, all 3 agents caused a fall in the methylation index (AdoMet/AdoHcy) but no or an inconsistent effect on the level of cyclic AMP [60-92-4]. An increase in the level of AdoHcy was obsd. already after 1 h of incubation, but was more pronounced after 4 h of preincubation with the adenosine derivs. The inhibition of cytotoxicity was mainly on their initiation of lysis, with a smaller effect on target cell binding. Antibody-dependent cellular cytotoxicity and lectin-dependent cellular cytotoxicity appeared to be less sensitive to inhibition by c3-ado. Thus, several adenosine analogs inhibit NK-cell-mediated cytotoxicity in parallel with a decreased methylation index. Apparently, a methylation step is crit. in lymphocyte-mediated cytotoxicity and NK cell activity is more sensitive to inhibition of this step than antibody- or lectin-dependent cytotoxicity.

Effect of cobalamin inactivation on folate-dependent transformylases involved in purine synthesis in rats

Effect of cobalamin inactivation on folate-dependent transformylases involved in purine synthesis in rats. Deacon, Rosemary; Perry, Janet; Lumb, Michael; Chanarin, Israel (MRC Clin Res. Cent., Northwick Park Hosp., Harrow/Middx. HA1 3UJ, UK). Biochem. J., 227(1), 67-71 (English) 1985. CODEN: BIJOAK. ISSN: 0306-3275. DOCUMENT TYPE: Journal CA Section: 18 (Animal Nutrition) N2O oxidizes and inactivates cobalamin [13408-78-1] and rats exposed in this way serve as models for cobalamin deficiency. Such animals show a fall in liver activity of glycinamide ribotide transformylase [9032-02-4] and a rise in that of 5-amino-4-imidazolecarboxamide ribotide transformylase [9032-03-5]. The fall in glycinamide ribotide transformylase activity was prevented by parenteral 5'-methylthioadenosine [2457-80-9] derived from methionine. Methylthioadenosine in turn is converted into formate. Activity of glycinamide ribotide transformylase recovers after 7 days despite continued N2O inhalation, and this is probably related to restoration of methionine synthesis by induction of betaine:homocysteine transmethylase.