Monoglutamates

In this reaction sequence acetic acid synthesis requires methyl transfer as CH3 to a Co(I)-corrin by N2 5-methyltetrahydrofolate monoglutamate to give a methylcorrinoid intermediate which is carboxylated to give a carboxymethylcorrinoid. This carboxymethylcorrinoid would then be reductively removed by NADPH to give acetic acid and regenerate the Co(I)-corrin. In contrast to the methyl-transfer proposed for the methionine synthetase reaction, this mechanism suggests that CH3-stabilized by Co attacks CO2 to give a carboxymethylcorrinoid intermediate. 

Most of the folates that occur naturally in man are polyglutamates,46 although they are transported as monoglutamates. 4 7... 

J. R. Bertino, P. F. Nixon, and A. Nahas, Mechanism of uptake of folate monoglutamates and their metabolism. In Folic Acid Biochemistry and Physiology in Relation to Human Nutrition Requirements, National Academy of Sciences, Washington, D. C. 1977, p. 178. 

Pharmacokinetics Oral synthetic folic acid is a monoglutamate and is completely absorbed following administration, even in the presence of malabsorption syndromes. 

Folate is the generic name used to refer to a family of vitamers with related biological activity. Instead, folic acid (pteroylglutamin acid, PGA) (Fignre 19.16) refers to the most oxidized, stable, and easily adsorbable synthetic form (monoglutamate). It is commonly nsed in food supplements and in food fortification because of its stability and becomes biologically active after redaction. 

Melse-Boonstra, A., Verhoef, P, Konings, E. J., Van Dusseldorp,M., Matser, A., Hollman, P. C.,Meyboom, S., Kok, F. J., West, C. E. (2002). Influence of processing on total, monoglutamate and polyglutamate folate contents of leeks, cauliflower, and green beans. J. Agric. Food Chem., 50, 3473-3478. 

Much of the folacin in food is present as conjugated pteroyl polyglutamates. Soybean contains 40% monoglutamate analogues, but in cabbage 90% of folic acid is present in forms... 

LT Vahteristo, V Ollilainen, P Varo. Liquid chromatographic determination of folate monoglutamates in fish, meat, egg, and dairy products consumed in Finland. J AOAC Int 80 373-378, 1997. 

LT Vahteristo, V Ollilainen, PE Koivistoinen, P Varo. Improvements in the analysis of reduced folate monoglutamates and folic acid in food by high-performance liquid chromatography. J Agric Food Chem 44 477-482, 1996. 

Both sequential and non-sequential types of oral contraceptives impair the absorption of polyglutamic folate but not that of monoglutamic folate the change can result in megaloblastic anemia in predisposed subjects, for example those with celiac disease or having a deficient diet (182). 

The monoglutamate N 5-methyltetrahydrofolate is subsequently transported into the bloodstream by both active and passive transport and is then widely distributed throughout the body. Inside cells, N 5-methyltetrahydrofolate is converted to tetrahydrofolate by the demethylation reaction that requires vitamin B12 (Figure 33-2, reaction 1). 

Occasionally, protein hinding of a vitamin on foods increases its absorption and hence its biological availability. For example, folate from milk is considerably better absorbed than that from either mixed food folates or free folic acid (Section 10.2.1). Folate bound to a specific binding protein in milk is absorbed in the Ueum, whereas free folate monoglutamate is absorbed in the (smaller) jejunum... 

As shown in Figure 10.1, folic acid consists of a pteridine linked at C-9 to p-aminobenzoic acid, forming pteroic acid. The carboxyl group of the p-aminobenzoic acid moiety is linked by a peptide bond to the amino group of glutamate, forming pteroyl monoglutamate. 

Although the terms folic acid and folate are often used interchangeably, correctly/ofic acid refers to the oxidized compound, pteroyl monoglutamate, and the various tetrahydrofolate derivatives are collectively known as folates. 

The folate in foods consists of a mixture of the different one-carbon substituted derivatives, with varying numbers of conjugated glutamyl residues. The biological availability of these vitamers differs and is consistently lower than that of free folic acid (pteroyl monoglutamate), which is the compound that... 

Because conjugase is a zinc metallo-enzyme, zinc deficiency can impair the absorption of conjugated food folates, but not folate monoglutamate. 

Conjugase responds rapidly to zinc depletion and repletion, and it has been suggested that the absorption of a test dose of folate polyglutamates may provide a sensitive index of zinc nutritional status (Canton and Cremin, 1990). The absorption of folate monoglutamates (from pharmaceutical preparations or foods) is not affected. 

Demethylated tetrahydrofolate monoglutamate is released hy extrahepatic tissues and is transported hound to a plasma folate binding protein similar to that in milk. It has a very low affinity for methyl-tetrahydrofolate and other one-carbon substituted derivatives. It functions mainly to return folate to the liver, where it is either conjugated for storage or methylated to 5-methyl-tetrahydrofolate that is secreted in the bile. 

---