Reaction of tetrahydrofolic acid with cyanate from urea solutions: formation of an inactive folate derivative.

Liver extracts prepared in 6 M urea contain significantly less microbiologically assayable folates than extracts prepared in hot 1% ascorbate. The possibility that inactive folate derivatives are formed by reaction with the cyanate present in the urea solution was investigated. Doubly labeled 2-14C, 3',5',9(n)-3H tetrahydrofolic acid reacted under hydrogen with sodium cyanate gave a compound which, after acidification to remove excess cyanate, shows a single UV absorbing peak at 285 nm. The 14C/3H ratios of starting material and product were the same. Reaction of 14C urea with nonradioactive tetrahydrofolic acid yielded the 14C labeled derivative. The compound does not support Lactobacillus casei growth. It is postulated that folate inactivation in cyanate or thiocyanate treated patients and in uremic patients may have clinical significance.