Cyanocobalamin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Vitamin B12 is used in the body in two forms: Methylcobalamin and 5-deoxyadenosyl cobalamin. The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine. Methionine in turn is required for DNA methylation. 5-Deoxyadenosyl cobalamin is a cofactor needed by the enzyme that converts L-methylmalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of energy from proteins and fats. Furthermore, succinyl CoA is necessary for the production of hemoglobin, the substances that carries oxygen in red blood cells. Ergocalciferol¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Vitamin D2 is the form of vitamin D most commonly added to foods and nutritional supplements. Vitamin D2 must be transformed (hydroxylated) into one of two active forms via the liver or kidney. Once transformed, it binds to the vitamin D receptor that then leads to a variety of regulatory roles. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma. Vitamin D2 and its analogs appear to promote intestinal absorption of calcium through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. Pyridoxine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in the form of the coenzyme pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA). Riboflavin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase. Thiamine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux.
Pharmacology
Cyanocobalamin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Cyanocobalamin (Vitamin B12) is a water-soluble organometallic compound with a trivalent cobalt ion bound inside a corrin ring. It is needed for nerve cells and red blood cells, and to make DNA. Vitamin B12 deficiency is the cause of several forms of anemia. Ergocalciferol¿¡ ´ëÇÑ Pharmacology Á¤º¸ Used in the treatment of hypcalcemia and in dialysis-dependent renal failure. Ergoalcifediol (Vitamin D2) is a fat soluble steroid hormone precursor of vitamin D that contributes to the maintenance of normal levels of calcium and phosphorus in the bloodstream. Pyridoxine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities. Riboflavin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts. Thiamine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.
Cyanocobalamin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Very high (to specific plasma proteins called transcobalamins); binding of hydroxocobalamin is slightly higher than cyanocobalamin. Ergocalciferol¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ >99.8% Pyridoxine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 22% Riboflavin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 60% Thiamine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 90-94%
Half-life
Cyanocobalamin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Approximately 6 days (400 days in the liver). Ergocalciferol¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 19 to 48 hours (however, stored in fat deposits in body for prolonged periods). Pyridoxine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 15-20 days Riboflavin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 66-84 minutes
Absorption
Cyanocobalamin¿¡ ´ëÇÑ Absorption Á¤º¸ Readily absorbed in the lower half of the ileum. Ergocalciferol¿¡ ´ëÇÑ Absorption Á¤º¸ Readily absorbed from small intestine (proximal or distal), requires presence of bile salts. Pyridoxine¿¡ ´ëÇÑ Absorption Á¤º¸ The B vitamins are readily absorbed from the gastrointestinal tract, except in malabsorption syndromes. Pyridoxine is absorbed mainly in the jejunum. Riboflavin¿¡ ´ëÇÑ Absorption Á¤º¸ Vitamin B2 is readily absorbed from the upper gastrointestinal tract. Thiamine¿¡ ´ëÇÑ Absorption Á¤º¸ Absorbed mainly from duodenum, by both active and passive processes
Cyanocobalamin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic Ergocalciferol¿¡ ´ëÇÑ Biotransformation Á¤º¸ Within the liver, ergocalciferol is hydroxylated to ercalcidiol (25-hydroxyergocalciferol) by the enzyme 25-hydroxylase. Within the kidney, ercalcidiol serves as a substrate for 1-alpha-hydroxylase, yielding ercalcitriol (1,25-dihydroxyergocalciferol), the biologically active form of vitamin D2. Riboflavin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Thiamine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic
Toxicity
Cyanocobalamin¿¡ ´ëÇÑ Toxicity Á¤º¸ Anaphylactic reaction (skin rash, itching, wheezing)-after parenteral administration. ORL-MUS LD50 > 8000 mg/kg Ergocalciferol¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 23.7 mg/kg (Orally in mice); LD50 = 10 mg/kg (Orally in rats ); Nausea, vomiting and diarrhea, weight loss, irritability, weakness, fatigue, lassitude, and headache. Pyridoxine¿¡ ´ëÇÑ Toxicity Á¤º¸ Oral Rat LD50 = 4 gm/kg. Toxic effects include convulsions, dyspnea, hypermotility, diarrhea, ataxia and muscle weakness. Riboflavin¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available Thiamine¿¡ ´ëÇÑ Toxicity Á¤º¸ Thiamine toxicity is uncommon; as excesses are readily excreted, although long-term supplementation of amounts larger than 3 gram have been known to cause toxicity. Oral mouse LD50 = 8224 mg/kg, oral rat LD50 = 3710 mg/kg.
Drug Interactions
Cyanocobalamin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Ergocalciferol¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Pyridoxine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Riboflavin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Thiamine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
Cyanocobalamin¿¡ ´ëÇÑ Description Á¤º¸ Cyanocobalamin (commonly known as Vitamin B12) is the most chemically complex of all the vitamins. Cyanocobalamin's structure is based on a corrin ring, which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Cyanocobalamin cannot be made by plants or by animals, as the only type of organisms that have the enzymes required for the synthesis of cyanocobalamin are bacteria and archaea. Higher plants do not concentrate cyanocobalamin from the soil and so are a poor source of the substance as compared with animal tissues. Cyanocobalamin is naturally found in foods including meat (especially liver and shellfish), eggs, and milk products. [HMDB] Ergocalciferol¿¡ ´ëÇÑ Description Á¤º¸ Ergocalciferol (Vitamin D2) is a derivative of ergosterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from cholecalciferol in having a double bond between C22 and C23 and a methyl group at C24. [PubChem] Nicotinamide¿¡ ´ëÇÑ Description Á¤º¸ An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [PubChem] Pyridoxine¿¡ ´ëÇÑ Description Á¤º¸ The 4-methanol form of vitamin B 6 which is converted to pyridoxal phosphate which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990). [PubChem] Riboflavin¿¡ ´ëÇÑ Description Á¤º¸ Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as flavin mononucleotide and flavin-adenine dinucleotide. [PubChem] Thiamine¿¡ ´ëÇÑ Description Á¤º¸ 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride. [PubChem]