Folinic acid, structure

Methotrexate (MTX, chemical structure shown in Fig. 1.) competitively inhibits the dehyrofolate reductase, an enzyme that plays an essential role in purine synthesis. The dehydrofolate reductase regenerates reduced folates when thymidine monophosphate is formed from deoxyuridine monophosphate. Without reduced folates cells are unable to synthesize thymine. Administration of N-5 tetrahydrofolate or N-5 formyl-tetrahydrofolate (folinic acid) can bypass this block and rescue cells from methotrexate activity by serving as antidote. 

Both sulfonamides and trimethoprim (not a sulfonamide) sequentially interfere with folic acid synthesis by bacteria. Folic acid functions as a coenzyme in the transfer of one-carbon units required for the synthesis of thymidine, purines, and some amino acids and consists of three components a pteridine moiety, PABA, and glutamate (Fig. 44.1). The sulfonamides, as structural analogues, competitively block PABA incorporation sulfonamides inhibit the enzyme dihydropteroate synthase, which is necessary for PABA to be incorporated into dihydropteroic acid, an intermediate compound in the formation of folinic acid. Since the sulfonamides reversibly block the synthesis of folic acid, they are bacteriostatic drugs. Humans cannot synthesize folic acid and must acquire it in the diet thus, the sulfonamides selectively inhibit microbial growth. 

Lee, H., Reyes, V. M., Kraut, J. (1996) Crystal structures of Escherichia coli dihydrofolate reductase complexed with 5-formyltetrahydrofolate (folinic acid), in two space groups evidence For enolization of pteridine 04, Biochemistry 35, 7012-7020. 

Naturally occurring peptides of the pteroylglutamic acid (PGA) family and of folinic acid, such as p-aminobensoylpolyglutamic acid, are very closely related, by structure as well as by origin, and they may be considered as belonging to the same group. We will therefore discuss them together. 

In a study of the structure and functions of feruloylated pectins in primary cell walls in spinach, about one feruloyl group was found per sixty sugar residues ( ). Ferulic acid was determined after alkaline hydrolysis by the Folin-Ciocalteu phenol reagent. 

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