Genetic Aspects of Folate Metabolism

When two clonal lines of mouse fibroblasts, each containing a drug-resistant marker, are grown together for 4 days, hybrid cells can be detected by selective conditions. These hybrid cells are presumed to be the result of mating. By the same method evidence can be obtained which suggests that mating may be followed by segregation.

Normal young adult male and female subjects were maintained on fixed dietary regimens which were either essentially normal or were semisynthetic and curtailed in methionine and choline intakes and virtually free of cystine. The subjects maintained stable weights and remained in positive nitrogen balance or within the zone of sulfur equilibrium. Choline intakes were calculated, and urinary excretions of creatinine, creatine, and sacrosine were measured. Creatinine excretions of male subjects on essentially normal diets outweighed the total intakes of labile methyl groups. Taking into account the excretions of additional methylated compounds, as judged from published values, it appears that methyl neogenesis must normally play a role in both males and females. When labile methyl intake is curtailed, de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties. On the normal diets used in these experiments, the average homocysteinyl moiety in males cycled between methionine and homocysteine at least 1.9 times before being converted to cystathionine. For females, the average number of cycles was at least 1.5. When labile methyl intake was curtailed, the average number of cycles rose to 3.9 for males and 3.0 for females under the conditions employed.