Folic acid chemical structure

Special mention must be accorded to iatrogenic effects, where the usefulness of novel synthetic drugs is impaired by untoward side effects of obscure etiology. In some, if not many of them, these side effects may find their explanation in the inhibitory action of the drug upon a vitamin, as in the case of primidone vs. folic acid (B3a). These relationships appear to be fortuitous until the structural chemical kinship of drug and vitamin is recognized. 

The chemical structure of folate (or folic acid) is shown in Figure 5.8. In humans, folate usually occurs as polyglutamate derivatives. The active form of folate is THF, sometimes shown as FH4) is derived from folate via two reductase reactions. THF functions as a carrier of one-carbon groups in varying oxidation states (Table 5.1). 

Compared with other vitamins, the chemical structures of both folic acid and B12 are complex. They are prosthetic groups for the enzymes that catalyse the transfer of the methyl group (-CH3) between compounds (one-carbon metabolism). The -CH3 group is chemically unreactive, so that the chemistry for the transfers is difficult, requiring complex structures for catalysis. 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Folic acid is vital for both humans and bacteria. Bacteria synthesize this compound, but humans are unable to synthesize it and, consequently, obtain the necessary amounts from the diet, principally from green vegetables and yeast. This allows selectivity of action. Therefore, sulfa drugs are toxic to bacteria because folic acid biosynthesis is inhibited, whereas they produce little or no ill effects in humans. The structural relationships between carboxylic acids and sulfonic acids that we have observed in rationalizing chemical reactivity are now seen to extend to some biological properties. 

Strychnine is a famous poison featured in many detective stories and a molecule with a beautiful structure. All chemists refer to it as strychnine as the systematic name is virtually unpronounceable. Two groups of experts at IUPAC and Chemical Abstracts also have different ideas on the systematic name for strychnine. Others like this are penicillin, DNA, and folic acid. 

Figure 5.29. PAMAM dendrimer multifunctional conjugates for cancer treatment. The FA group is a folic acid cancer cell target, and FITC is fluorescein isothiocyanate, used as an imaging agent. Also shown (bottom) is the molecular structure for the anticancer drug, taxol, denoting the -OH group that covalently attaches to the dendrimer. Reproduced with permission from Majoros, I. J. Myc, A. Thomas, T Mehta, C. Baker, J. R. Biomacromolecules, 2006, 7, 572. Copyright 2006 American Chemical Society.

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

Fig. 1. Chemical structure of cofactors (a) NAD(P)+ and (b) NADH(P), with R = H is NAD+ or NADH, and R = P is NADP+ or NADPH, (c) Flavin mononucleotide (FMN), (d) Flavin adenine dinucleotide (FAD), (e)Tetrahydrofolate, (f) 10-formyltetrahydro-folic acid, (g) 5-10 methylenetetrahydrofolic acid,...

Fig. 20 The chemical structure of a thermotropic folic acid derivative 44 and its proposed self-assembly into smectic or columnar phases...

Fig. 4 Schematic picture of EPR effect. Tumor targeting of long-circulating polymer drug carrier occurs passively by the enhanced permeability and retention (EPR) effect. The inset is the chemical structure of folic acid...

Fig. 6 The chemical structure of folic acid and the series of distinct steps of the folate receptor-mediated endocytosis (adapted from Ref. [187] with permission)...

Folic acid was purified in the middle of the twentieth century, and research on the chemical structure of this compound and on its synthesis have been continuously conducted [1,2]. The first total synthesis of riboflavin was achieved in 1935 [3,4]. Riboflavin is a yellow compound, and its solutions emit a yellow-green fluorescence. Riboflavin is sensitive to light, and it gave lumiflavin when exposed to a light under basic conditions. Under neutral conditions it gave lumichrome by releasing the D-ribose moiety. 

A competitive inhibitor resembles the substrate in its chemical structure and is able to combine with the enzyme to form an enzyme-inhibitor complex. In so doing it competes with the substrate for the active sites of the enzyme, and formation of the enzyme-substrate complex is inhibited. This type of inhibition may be reversed by the addition of excess substrate, which displaces the inhibitor, forming normal enzyme-substrate complexes. One of the best-known examples is provided by the sulphonamide drugs. The synthesis of folic acid from p-aminobenzoic acid (PABA) is a vital metabolic process in the bacteria controlled by these drugs. The similarity between PABA and sulphanUamide, released by the sulphonamides, is obvious ... 

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