The metabolic consequences of vitamin B-12/methionine deficiency in rats

The synthesis of liver pteroylglutamates (folates) from injected [3-H]-pteroylglutamic acid was investigated in vitamin B-12 methionine-deficient rats and pair-fed controls using improved extraction and chromatographic procedures to identify the monoglutamyl derivatives present. Livers from deficient animals had significantly increased levels of radioactive 5-methyltetrahydropteroylglutamate detected after conjugase treatment of extracts and significantly decreased levels of radioactive tetrahydropteroylglutamate and formylated derivatives. However, that this is only a temporary effect and the result of a decreased rate of equilibration of the exogenous radioactivity was shown by measuring the fully equilibrated endogenous pools. This was done by microbiological assay of the endogenous liver folates with Lactobacillus casei. No significant difference was found between deficient animals and controls in the proportion of the endogenous microbiologically active derivatives present. These results in the rat do not support the idea that in vitamin B-12 deficiency the cellular folates accumulate as the reduced 5-methyl derivative, resulting in inadequate amount of the other cofactors to partipicate in nucleic acid biosynthesis.