Chemical and physical properties of folate Domina Petric, MD

Essential features of the chemical structure: Pteridine derivative Variable degree of hydrogenation of pteridine nucleus Single-carbon units can bind nitrogens at position 5 and/or 10 One or more glutamyl residues linked via peptide bonds December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical structures of the folate group: Web.squ.edu.om ChemSpider.com Pteroylglutamic acid Tetrahydrofolic acid December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Nomenclature Folate is the generic descriptor for folic acid (pteroylmonoglutamic acid) and related compounds exhibiting the biological activity of folic acid. The terms folacin, folic acids and folates are used only as general terms for this group of heterocyclic compounds based on the N-[(6-pteridinyl)methyl]-p-aminobenzoic acid skeleton conjugated with one or more L-glutamic acid residues. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Folates can consist of a mono- or polyglutamyl conjugate. Nomenclature Folates can consist of a mono- or polyglutamyl conjugate. These are named for the number of glutamyl residues (n), using such notations as PteGlun. The reduced compound tetrahydropteroylglutamic acid is called tetrahydrofolic acid. Its single-carbon derivatives are named according to the specific carbon moiety bound. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties The folates include a large number of chemically related species, each differing with respect to the various substituents possible at three sites on the pteroylglutamic acid basic structure. Each is a formal derivative of pteridine. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties With three known reduction states of the pyrazine nucleus, six different single-carbon substituents on N-5 and/or N-10, and as many as eight glutamyl residues on the benzene ring, more than 170 different folates are theoretically possible. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties The folates from most natural sources usually have a single carbon unit at N-5 and/or N-10. These forms participate in the metabolism of the single-carbon pool. The single carbon units that may be transported and stored by folates can vary in oxidation state from the methyl (5-CH3-FH4) to the formyl (5-HCO-FH4, 10-HCO-FH4). December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties Intracellular folates contain poly-γ-glutamyl chains usually of 2 to 8 glutamyl residues, sometimes extending to 12 in bacteria. Tissues contain enzymes called conjugases that hydrolytically remove glutamyl residues to release the monoglutamyl form (folic acid). December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties The folylpolyglutamates are the actual coenzyme forms active intracellularly and that the monoglutamates, which can pass through membranes, are transport forms. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties The folates have an asymmetric center at C-6. This introduces stereospecificity in the orientation of hydrogen atoms on reduction of the pteridine system. They add to carbons 6 and 7 in positions below the plane of the pyrazine ring. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties The UV absorption spectra of the folates are characterized by the independent contributions of the pterin and 4-aminobenzoyl moieties. Most have absorption maxima in the region of 280–300 nm. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties Folic acid (pteroylmonoglutamic acid) is an orange-yellow crystalline substance that is soluble in water, but insoluble in ethanol or less polar organic solvents. It is unstable to light, to acidic or alkaline conditions, to reducing agents, and except in dry form, to heat. It is reduced in vivo enzymatically first to 7,8-dihydrofolic acid (FH2) and then to FH4. Both of these compounds are unstable in aerobic environments and must be protected by the presence of an antioxidant (ascorbic acid, 2 mercaptoethanol). December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical and physical properties Two derivatives of folic acid, each having an amino group in the place of the hydroxyl at C-4, are folate antagonists of biomedical use: aminopterin (4-aminofolic acid) methotrexate (4-amino-N10-methylfolic acid) Aminopterin is used as a rodenticide. Methotrexate is an antineoplastic agent. December 6, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. December 6, 2018