Folic acid cobalamins

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Homocysteine-lowering treatment with folic acid, cobalamin and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction or hypercoagulability in patients with previous transient ischemic attack or stroke a randomized substudy of the VITATOPS trial. Stroke 36 144-146... 

Folic acid/cobalamin/pyridoxine hydrochloride are nutritional combinations. Folic acid and cobalamin reduce homocysteine by metabolizing it to methionine. Pyridox-ine facilitates breakdown of homocysteine to cysteine and other by-products. They are indicated for nutritional requirement of patients with end-stage renal failure, dialysis, hyperhomocysteinemia, homocystinuria, nutrient malabsorption or inadequate dietary intake, particularly for patients with or at risk for cardiovascular disease, cerebrovascular disease, peripheral vascular disease, arteriosclerotic... 

Homocysteine is an intermediate in biosynthesis of cysteine, methionine, and in the breakdown of methionine. Recent research has indicated that elevated levels of homocysteine may correlate with increased incidence of vasuclar disease. Supplementation of diets with folic acid, cobalamin and pyridoxine appear to provide protection by lowering homocysteine levels in the blood. 

Coronary heart disease Folic acid Cobalamin (vitamin B12) Pyridoxine (vitamin Be) Homocysteine reduction MA of RCTs supplementation in patients does not affect risk of a recurrent event Clarke et al. (2010)... 

B,2 Cobalamin Coenzyme in transfer of one-carbon fragments and metabolism of folic acid Pernicious anemia = megaloblastic anemia with degeneration of the spinal cord... 

Patients typically present by 6-12 months with severe developmental retardation, convulsions, microcephaly and homocysteinemia (=50pmol/l) with hypomethioninemia (<20 pmol/1). A few individuals have had psychiatric disturbances. The blood concentration of vitamin B12 is normal, and, unlike individuals with defects of cobalamin metabolism, these patients manifest neither anemia nor methylmalonic aciduria. The blood folic acid level is usually low. 

A relatively large number of agents have been utilized to treat this intractable disorder folinic acid (5-formyl-tetrahydrofolic acid), folic acid, methyltetrahydrofolic acid, betaine, methionine, pyridoxine, cobalamin and carnitine. Betaine, which provides methyl groups to the beta i ne ho mocystei ne methyltransferase reaction, is a safe treatment that lowers blood homocysteine and increases methionine. 

Cobalamin, 25 803 folic acid and, 25 802 Cobalt (Co), 7 207-228. See also Co-base superalloys 60Co isotope 60Co nucleus Fe-Ni-Co alloys Dicobalt octacarbonyl Tetracobalt dodecacarbonyl analysis, 7 215-216 in ceramic-matrix composites, 5 554t coke formation on, 5 266 colloidal suspensions, 7 275 economic aspects, 7 214-215 effect on copper resistivity, 7 676t environmental concerns, 7 216 health and safety factors, 7 216-218 in M-type ferrites, 11 66, 69 occurrence, 7 208... 

Hypervitaminosis A, 25 789 Hypervitaminosis biotin, 25 800 Hypervitaminosis cobalamin, 25 804 Hypervitaminosis D, 25 792 Hypervitaminosis E, 25 794 Hypervitaminosis folic acid, 25 803 Hypervitaminosis K, 25 795 Hypervitaminosis niacin, 25 798 Hypervitaminosis niacinamide, 25 798 Hypervitaminosis pantothenic acid, 25 799 Hypervitaminosis pyridoxine, 25 799 Hypervitaminosis riboflavin, 25 797 Hypervitaminosis thiamine, 25 796 Hyphenated techniques... 

The structure of cobalamin is more complex than that of folic acid (Figure 15.2 and 15.3). At its heart is a porphyrin ring containing the metal ion cobalt at its centre. In catalytic reactions the cobalt ion forms a bond with the one-carbon group, which is then transferred from one compound to another. Vitamin B12 is the prosthetic group of only two enzymes, methylmalonyl-CoAmutase and methionine synthase. The latter enzyme is particularly important, as it is essential for the synthesis of nucleotides which indicates the importance of vitamin B12 in maintenance of good health. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

Fig. 1. Folate-cobalamin interaction in the synthesis of purines and pyrimidines and, therefore, of DNA. (1) In gastrointestinal mucosa cells (2) in the liver (3) in peripheral tissues. C, cobalamine DAC, desoxyadenosylcobalamine HC, hydroxy cobalamine MC, methylcobalamine F, folic acid MTHF, methyltetrahydrofolic acid THF, tetrahydrofolic acid DHF, dihydrofolic acid dUMP, deoxyuridinemonophosphate dTMP, deoxythymidine-monophosphate. (Adapted from Far-...

Contraindications Folic acid deficiency anemia, hereditary optic nerve atrophy, history of allergy to cobalamins... 

The major vitamins are described in separate alphabetical entries in tins book. Titles used for these entries have been selected on tlie basis of the most frequently used designations as of tlie early 1980s. In alphabetical order, the vitamins described in this book are Ascorbic Acid (Vitamin C) Biotin Choline and Cholinesterase Folic Acid Inositol Niacin Pantothenic Acid Vitamin Bj (Riboflavin) Thiamine (Vitamin Bj) Vitamin A Vitamin B (Pyridoxine) Vitamin B12 (Cobalamin) Vitamin D Vitamin E and Vitamin K. 

Homocysteine-lowering therapy is lifesaving for patients with severe hyperhomocysteinemia due to CBS deficiency. Approximately 50% of patients respond to treatment with pharmacological doses (100 to 800 mg daily) of pyridox-ine (a form of vitamin B6). Adjunctive therapy may include betaine (2 to 6 g daily), folic acid (5 to 10 mg daily), or cobalamin (0.05 to 1.0 mg daily), or methionine restriction. Long-term homocysteine-lowering therapy substantially decreases cardiovascular risk in these patients. 

Deficiency of folic acid leads to a megaloblastic anaemia because it is necessary for the production of purines and pyrimidines, which are essential precursors of deoxyribonucleic acid (DNA). The megaloblastic marrow of cobalamin deficiency is due to interference with folic acid utilisation and the morphological changes of cobalamin deficiency can be reversed by folic acid. It is vital to realise that folic acid does not provide adequate treatment for pernicious anaemia. Nor does vitamin 3 2 provide adequate treatment for the megaloblastic anaemia of folic acid deficiency, although a partial response may occur because vitamin plays a role in folate metabolism. 

Vitamins are divided into two major categories. They are fat-soluble (A, D, E and K) and water-soluble vitamins (B-complex and vitamin C). B complex vitamins include thiamine (Bi), riboflavin (B2), pantothenic acid (B3), niacin (B5), pyridoxine (Be), biotin (By), folic acid (B9), and cobalamin (Biy). Inositol, cholic and para-aminobenzoic acid are vitamin-like substances sometimes classified as part of the B complex, but no convincing evidence has been shown so far to be included as vitamins. All the fat-soluble vitamins and some B vitamins exist in multiple forms. The active forms of vitamin A are retinol, retinal and retinoic acid and vitamin D is available as ergocalciferol (D2) and cholecalciferol (D3). The vitamin E family includes four tocopherols and four tocotrienols but a-tocopherol being the most abundant and active form. The multiple forms of vitamins are interconvertible and some are interchangeable. 

The coenzyme form of pantothenic acid is coenzyme A and is represented as CoASH. The thiol group acts as a carrier of acyl group. It is an important coenzyme involved in fatty acid oxidation, pyruvate oxidation and is also biosynthesis of terpenes. The epsilon amino group of lysine in carboxylase enzymes combines with the carboxyl carrier protein (BCCP or biocytin) and serve as an intermediate carrier of C02. Acetyl CoA pyruvate and propionyl carboxylayse require the participation of BCCP. The coenzyme form of folic acid is tetrahydro folic acid. It is associated with one carbon metabolism. The oxidised and reduced forms of lipoic acid function as coenzyme in pyruvate and a-ketoglutarate dehydrogenase complexes. The 5-deoxy adenosyl and methyl cobalamins function as coenzyme forms of vitamin B12. Methyl cobalamin is involved in the conversion of homocysteine to methionine. 

Folic acid and vitamin B]2 metabohsm are linked by the reaction that transfers a methyl group from 5-MTHF to cobalamin. In cases of cobalamin deficiency, folate is trapped as 5-MTHF and is metabolically dead. It cannot... 

There is reason to conclude that vitamin deficiency might contribute to arteriosclerosis. There is a correlation between elevated homocysteine levels and incidence of cardiovascular disease (59). There is debate as to whether homocysteine contributesto the dam e of cells on the interior of blood vessel or whether homocysteine is a marker of intensive cell repair and formation of replacement cells. Nevertheless, administration of pyridoxine, folic acid, and (yanocobalamin are being recommended along with the two antioxidant vitamins, a-tocopherol and ascorbic acid for arteriosclerosis. Vitamin Bg is required for two of the steps in the catabolism of homocysteine to succinyl CoA (Fig. 8.52). Note in Fig. 8.52 (bottom) that biotin and a coenzyme form of cobalamin also are required for... 

Because all vitamins are essential, it is difficult to state that one vitamin is more important than another. Nevertheless, folic acid, with its coenzyme role in purine biosynthesis, can be considered crucial for some of the cells most fundamental biochemistry, cell division. This vitamin is intimately tied to vitamin (cobalamin), which has made estimating its DRIs difficult. Also, conditions that can cause a folic acid deficiency also can result in a vitamin Bi2 deficiency. 

The most reduced coenzyme is 5-methyl tetrahydrofolate poly glutamate. It is the source of the methyl group added to homocysteine regenerating methionine and tetrahydrofolate ready to accept a one-carbon unit from formate or serine. This last reaction is where folic acid and vitamin come together (Figs. 8.49, 8.52, and 8.53). The implications of this reaction and how folic acid can mask pernicious anemia are discussed in the seetion on vitamin Big (cyanocobalamin). Note that the formation of 5-methyl-THF nor-mdly is not reversible. Tetrahydrofolate can be regenerated only if there is adequate methyl cobalamin coenzyme. 

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