Biotin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids. Calcium¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than 500 human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca2+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is 1,500 milligrams per day for women not taking estrogen and 800 milligrams per day for women on estrogen. There is close to 300 milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available. 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. Glycine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia. Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS. L-alanine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ L-Alanine is a non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. BCAAs are used as a source of energy for muscle cells. During prolonged exercise, BCAAs are released from skeletal muscles and their carbon backbones are used as fuel, while their nitrogen portion is used to form another amino acid, Alanine. Alanine is then converted to Glucose by the liver. This form of energy production is called the Alanine-Glucose cycle, and it plays a major role in maintaining the body's blood sugar balance. L-arginine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.
Pharmacology
Biotin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or "cradle cap". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes. 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. Glycine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Helps trigger the release of oxygen to the energy requiring cell-making process; Important in the manufacturing of hormones responsible for a strong immune system. L-alanine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Is an important source of energy for muscle tissue, the brain and central nervous system; strengthens the immune system by producing antibodies; helps in the metabolism of sugars and organic acids. L-arginine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.
Absorption
Biotin¿¡ ´ëÇÑ Absorption Á¤º¸ Systemic - approximately 50% 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. Glycine¿¡ ´ëÇÑ Absorption Á¤º¸ Absorbed from the small intestine via an active transport mechanism. L-arginine¿¡ ´ëÇÑ Absorption Á¤º¸ Absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.
Biotin¿¡ ´ëÇÑ Toxicity Á¤º¸ Prolonged skin contact may cause irritation. 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. Glycine¿¡ ´ëÇÑ Toxicity Á¤º¸ ORL-RAT LD50 7930 mg/kg, SCU-RAT LD50 5200 mg/kg, IVN-RAT LD50 2600 mg/kg, ORL-MUS LD50 4920 mg/kg; Doses of 1 gram daily are very well tolerated. Mild gastrointestinal symptoms are infrequently noted. In one study doses of 90 grams daily were also well tole. L-arginine¿¡ ´ëÇÑ Toxicity Á¤º¸ Oral supplementation with L-arginine at doses up to 15 grams daily are generally well tolerated. The most common adverse reactions of higher doses from 15 to 30 grams daily are nausea, abdominal cramps and diarrhea. Some may experience these symptoms at lower doses.
Drug Interactions
Biotin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Calcium¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Alendronate Formation of non-absorbable complexesAmprenavir The antiacid decreases the absorption of amprenavirAtazanavir This gastric pH modifier decreases the levels/effects of atazanavirChloroquine The antiacid decreases the absorption of chloroquineCiprofloxacin Formation of non-absorbable complexesDapsone Formation of non-absorbable complexesDelavirdine The antiacid decreases the effect of delavirdineDemeclocycline Formation of non-absorbable complexesDoxycycline Formation of non-absorbable complexesEnoxacin Formation of non-absorbable complexesFosamprenavir The antiacid decreases the absorption of amprenavirGrepafloxacin Formation of non-absorbable complexesIbandronate Formation of non-absorbable complexesIndinavir The antiacid decreases the absorption of indinavirItraconazole The antacid decreases the effect of the imidazoleKetoconazole The antacid decreases the effect of the imidazoleLevofloxacin Formation of non-absorbable complexesLevothyroxine Calcium decreases absorption of levothyroxineLomefloxacin Formation of non-absorbable complexesMethacycline Formation of non-absorbable complexesMinocycline Formation of non-absorbable complexesMoxifloxacin Formation of non-absorbable complexesNorfloxacin Formation of non-absorbable complexesOfloxacin Formation of non-absorbable complexesOxytetracycline Formation of non-absorbable complexesPefloxacin Formation of non-absorbable complexesPolystyrene sulfonate Formation of non-absorbable complexesRisedronate Formation of non-absorbable complexesTetracycline Formation of non-absorbable complexesTrovafloxacin Formation of non-absorbable complexesClodronate Formation of non-absorbable complexesEtidronic acid Formation of non-absorbable complexesMycophenolate mofetil Formation of non-absorbable complexesTemafloxacin Formation of non-absorbable complexes Cyanocobalamin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Ergocalciferol¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Glycine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available L-arginine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
Biotin¿¡ ´ëÇÑ Description Á¤º¸ A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk. [PubChem] Calcium¿¡ ´ëÇÑ Description Á¤º¸ Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. 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] Glycine¿¡ ´ëÇÑ Description Á¤º¸ A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [PubChem] L-alanine¿¡ ´ëÇÑ Description Á¤º¸ A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [PubChem] L-arginine¿¡ ´ëÇÑ Description Á¤º¸ An essential amino acid that is physiologically active in the L-form. [PubChem]