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Title: Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.
Authors:
; ;
Publication Date:
OSTI Identifier:
6117790
Resource Type:
Journal Article
Resource Relation:
Journal Name: Life Sci.; (United States); Journal Volume: 31:18
Research Org:
South African Inst. for Medical Research, Johannesburg, South Africa
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; NERVOUS SYSTEM; INJURIES; NITROUS OXIDE; BIOLOGICAL EFFECTS; VITAMIN B-12; INACTIVATION; BATS; FOLIC ACID; METHIONINE; RESPONSE MODIFYING FACTORS; AMINO ACIDS; ANIMALS; CARBOXYLIC ACIDS; CHALCOGENIDES; DRUGS; HEMATINICS; HEMATOLOGIC AGENTS; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; LIPOTROPIC FACTORS; MAMMALS; NITROGEN COMPOUNDS; NITROGEN OXIDES; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; OXIDES; OXYGEN COMPOUNDS; PTERIDINES; VERTEBRATES; VITAMIN B GROUP; VITAMINS 560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)