Effect of cobalamin inactivation on folate-dependent transformylases involved in purine synthesis in rats.
N2O oxidizes and inactivates cob[I]alamin, and animals exposed in this way serve as models for cobalamin 'deficiency'. Such animals show a fall in activity of glycinamide ribotide transformylase and a rise in that of 5-amino-4-imidazolecarboxamide ribotide transformylase. The fall in glycinamide ribotide transformylase activity was prevented by parenteral 5'-methylthioadenosine 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.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003839:Deoxyadenosines; D019877:Hydroxymethyl and Formyl Transferases; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000494:pharmacology; D009609:Nitrous Oxide / Q000494:pharmacology; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; D051026:Phosphoribosylglycinamide Formyltransferase; D011687:Purines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013872:Thionucleosides / Q000494:pharmacology; D014805:Vitamin B 12 / Q000494:pharmacology*
D003839:Deoxyadenosines; D011687:Purines; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D008715:Methionine; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; D000217:Acyltransferases; D009609:Nitrous Oxide; D000241:Adenosine; D014805:Vitamin B 12