Folates biochemical function

Biochemical Functions. Ascorbic acid has various biochemical functions, involving, for example, coUagen synthesis, immune function, dmg metabohsm, folate metaboHsm, cholesterol cataboHsm, iron metaboHsm, and carnitine biosynthesis. Clear-cut evidence for its biochemical role is available only with respect to coUagen biosynthesis (hydroxylation of prolin and lysine). In addition, ascorbic acid can act as a reducing agent and as an effective antioxidant. Ascorbic acid also interferes with nitrosamine formation by reacting direcdy with nitrites, and consequently may potentially reduce cancer risk. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

The biochemical functions of folate were first determined with bacteria. Folate plays a major role in carrying one-carbon units within cells. In the brush border of mucosal cells, the polyglutamyl chain is removed by the enzyme folate conjugase and folate monoglutamate is subsequently absorbed. Folate acts as both a donor and receiver of one-carbon moieties in a variety of reactions. 

The biochemical functions of folate were first determined as a growth factor for Streptococcus lactis. 

Biochemical Function, Consequences of Folate Deficiency and Health Alteration... 

In summary, the biochemical function of folate coenzymes is to transfer and use these one-carbon units in a variety of essential reactions (Figure 2), including de novo purine biosynthesis (formylation of glycinamide ribonucleotide and 5-amino-4-imidazole carboxamide ribonucleotide), pyrimidine nucleotide biosynthesis (methylation of deoxyuridylic acid to thy-midylic acid), amino-acid interconversions (the interconversion of serine to glycine, catabolism of histidine to glutamic acid, and conversion of homocysteine to methionine (which also requires vitamin B12)), and the generation and use of formate. 

Folic acid and its metabolites called folates are essential to the cell s functions. They act as coenzymes in many biochemical processes. Folate-dependent enzymes are vital to rapidly dividing cell populations, such as the neoplastic or normal-stem cells. Therefore, they are a target for anti-folates in anti-cancer treatment. 

Moat SJ, Lang D, McDowell IF, Clarke ZL, Madhavan AK, Lewis MJ, Goodfellow J (2004) Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem 15 64-79... 

Said HM, Nguyen TT, Dyer DL et al. (1996) Intestinal folate transport identification of cDNA involved in the folate transport and the functional expression and distribution of its mRNA. Biochem Biophys Acta 1281 164-172... 

Experimental animals that have been exposed to ititrous oxide to deplete vitamin B12 show an increase in the proportion of liver folate present as methyl-tetrahydrofolate (85% rather than the normal 45%), largely at the expense of unsubstituted tetrahydrofolate and increased urinary loss of methyl-tetrahydrofolate (Horne et al., 1989). Tissue retention of folate is impaired because methyl-tetrahydrofolate is a poor substrate for polyglutamyl-folate synthetase, compared with unsubstituted tetrahydrofolate (Section 10.2.2.1). As a result of this, vitamin B12 deficiency is frequently accompanied by biochemical evidence of functional folate deficiency, including impaired metabolism of histidine (excretion of formiminoglutamate Section 10.3.1.2) and impaired thymidylate synthetase activity (as shown by abnormally low dUMP suppression Section 10.3.3.3), although plasma concentrations of methyl-tetrahydrofolate are normal or elevated. 

Vitamins are essential lead compounds for the development of novel radiopharmaceuticals. Many vitamin receptors such as the folate receptor are overexpressed on different tumor cell lines (Parker et al. 2005). Biotin labeled with Tc is under investigation since many years in different settings. A vitamin that has not found as much interest as hiotin is vitamin B12. Since it is a relatively large molecule, it has heen proposed to use B12 as a Trojan horse since rapidly proliferating cells and some bacterial stems show a high demand for this growth essential vitamin. While research toward labeled folate and B12 has intensified over the past couple of years, research with biotin rather slowed down. The biochemical pathways of folate and B12 are interlinked since folate delivers the -CH3 group to the apoenzyme in order to activate it toward its function in the methionine synthase cycle. 

Rosenblatt, S, and Erbe, R. W. (1973) Reciprocal changes in the levels of functionally related folate enzymes during the culture cycle in known fibroblasts, Biochem. Biophys. Res. Commun., 54 1627,... 

It is hypothesised that another condition which predisposes to the development of HOC is malnutrition. Alcohol can affect the blood levels and metabolism of a variety of other spedes important for biochemical synthesis and physiological function. DNA methylation can be affeded by diminished absorption and metabolism of micronutrients such as folate and vitamins B12 and Bg. ritamin A and P-carotene can also be present at below normal levels in alcoholics. 

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