Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Coenzymes — special naturally occurring specialized reagents
Tetrahydrofolic acid and other pterin coenzymes
Coenzyme forms of folic acid

The Coenzymes responsible for The transfer of single-carbon units are derivatives of 5,6,7,8-tetrahydrofolic acid (abbreviated as H₄PteGlu or H₄Fol):

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The coenzyme forms of Folic acid occur in extremely low concentrations and are readily oxidized in air, which complicates their investigation. Alongside tetrahydrofolic acid, which contains a single L-glutamic acid residue, there are coenzymes in the form of conjugated compounds featuring additional L-glutamic acid residues attached via an amide bond—always formed through the terminal $\gamma$-carboxyl rather than the $\alpha$-carboxyl group. These coenzyme forms may contain anywhere from one to seven glutamic acid residues; with few exceptions, the distribution and BIOLOGICAL Functions OF these various forms remain unknown. The bacterium Clostridium acidi-urici contains exclusively triglutamate derivatives [156] and possesses at least one enzyme displaying absolute Specificity for H₄Fol-glutamic acid. Meanwhile, the serum of many animals contains only derivatives of folic acid itself. Pteroylpentaglutamate serves as the primary folic acid derivative in rat Liver.

Upon reduction, a new chiral center is created at C-6. The enzymatically active form of H₄Fol exhibits a negative optical rotation at 589 nm and is designated as (—)H₄Fol. However, since certain forms display a positive rotation, The Use of the designation (l) has been proposed [156].

Supplement 8-C

Folic acid (Pteroylglutamic acid)

In 1931, Wills, working in India, observed that patients suffering from tropical macrocytic anemia—characterized by enlarged red Blood Cells and a decreased red Cell count—could be cured by Dietary intake of liver or Yeast extracts. This condition could be induced in monkeys maintained on a local diet; a similar anemia can also be induced in chicks.

By 1938, it was further established that chicks require a growth factor present in yeast, alfalfa, and other Materials. Shortly after it was determined that this novel vitamin was also an essential nutrient for Lactobacillus casei and Streptococcus faecalis R¹⁾, the compound was successfully isolated. Spinach is also rich in this substance, which was named folic acid (derived from the same ROOT as the word "foliage").

The observation that the requirement of Streptococcus faecalis for folic acid can be fulfilled by a mixture of thymine, Serine, and a purine base provided a crucial clue to the metabolic functions of folic acid, which is required for The Biosynthesis of all these compounds. Based on the finding that certain E. coli mutants require either serine or Glycine for growth, it was hypothesized that the vitamin participates in the interconversion of Serine and Glycine. Isotopic labeling experiments demonstrated that in rats, as well as in Yeasts of the genus Torulopsis, serine and glycine are capable of interconversion. It was also shown that the extent of this interconversion decreases under conditions of Folic acid deficiency in rats.

¹⁾ The microbiologically active forms were actually di- and triglutamate derivatives, a circumstance that prompted the Description of the history of folic acid as "the most tangled chapter in The history of the vitamin B complex" [Wagner A.F., Folkers K. (1964). In: Vitamins and Coenzymes, Wiley (Interscience, New York, p. 114].