The nutritional requirements of the human body can rarely be met through a well balanced diet; dietary supplements, including vitamins and minerals are often required to sustain good or optimum health.
Coenzyme-A Technologies Inc.has applied new technology to the formulation and manufacture of a series of proprietary products, which address nutritional deficiencies that result from:
The stress of modern day living, chemical imbalances within the body, pesticides (biologically persistent and ubiquitous toxins) including certain prescription medications and the effects of aging.
These nutraceutical products are the first to provide the human body with a balanced combination of highly active nutritional components and substrates (Chemically bonded) that can be used by the body to support the synthesis and utilization of Coenzyme-A the metabolic enzyme. In addition, certain products also contain their own set of specific substances and nutrient/ substrates that support Coenzyme-A correction or alleviation of particular conditions associated with certain nutritional deficiencies and clinical impairments. It's important to know Coenzyme-A Technologies, Inc. scientific rationale in reference to its product the Coenzyme-ATM a dietary supplement.
Approximately 99% of the dietary /nutraceutical supplement Coenzyme A, is chemically bonded to an intermediate byproduct in the endogenous biosynthesis of the molecule Coenzyme A. Upon ingestion, where it is absorbed within the intestinal lumen, it primarily undergoes hydrolysis via the formation of Pantetheine and dephosphopantetheine there within the intestinal cells. Initiated readily by both sodium-dependent active transport mechanism and by passive diffusion. After absorption it is transported to body tissues via the blood, primarily as bound forms in erythrocytes. Maximum plasma response after oral ingestion was observed 2-4.5 hours followed by rapid declining in concentrations. Analysis of Pantothenate, usually in the form of CoA- containing species (eg, acetyl CoA, Succinyl CoA) content of rat tissues in clinical studies showed high concentrations in the areas of the heart, kidneys and the liver.
Endogenous synthesis of both CoA and ACP begins within the cells as it undergoes Phosphorylation reactions. This is the first and apparently a rate- limiting, biosynthetic enzymatic process where it is catalyzed by the Pantothenate Kinase enzyme. This is a magnesium-depended enzyme, resulting in the formation of Pantetheine 4’- Phosphate or (4-PP) an intermediate product in the endogenous biosynthesis of Coenzyme A. This is a primary, regulatory point of CoA synthesis, which then is unfortunately inhibited by the end products (high levels of CoA). This inhibitory action under experimental conditions in rat hearts has been reversed and bypassed with the addition of certain nutrient/ substrates as found in our formula. Although degradative enzymes exist for the breakdown of CoA, the scattered location of these enzymes within the cell appear to indicate that the cell is geared to minimize degradation of CoA once it has been formed within. Coenzyme A is formed by the sequential transfer of Adenosine 5’-Monophosphate and modified by a 3’- hydroxyl phosphate. 4’Phosphopantetheine is also found linked to various proteins, particularly those involved in fatty acid metabolism (Plesofsky- Vig, 1999). The ultimate site for CoA synthesis is assumed to be the mitochondrion as the majority of CoA (which normally does not cross the mitochondrial membrane) is found within these organelles. In addition to linkage to Diphospho-Adenosine in CoA, 4’-Phosphopantetheine can also be covalently linked to amino acids in a number of cellular proteins.
With the addition of certain (nutrient/substrates) to our formula the requirements for the transport of activated acyls, namely acyl- Co-As, across the inner mitochondrial membrane have been satisfied. Fatty acids are found in free form in the cytoplasm and needed to be transported across the inner mitochondrial membrane in a controlled fashion.
The activated fatty acid is first transferred by a mitochondrial outer membrane protein Carnitine Acyl Transferase I (1) complex from acyl-Co-A to acyl-Carnitine. The later is than transported across the inner membrane into the matrix compartment by Carnitine Acyl Translocase. There the fatty acids are reesterfied with a Co-A unit by the matrix enzyme complex Carnitine Acyl Transferase II.
The above are the intricate interactions with Coenzyme A, in which they exert a primary role with any Co-A- depended process and transport mechanisms involved in the mitochondrial metabolism. These substrates are further catalyzed by several acyl Transferases, which generally are classified on the bases of their affinity for acyl CoA.
An increase in Co-ASH availability or a decrease in acyl- Co-A levels expands the roles of these (nutrient/ substrates) to different choices, including the removal of inhibitory metabolites and the modulation of key enzymatic processes. In addition some of the nutrient esters appear to specifically modify cellular metabolism, structure and function in order to accommodate certain metabolic conditions.
The process of Beta-Oxidation is named after the carbon atom in the beta position of the fatty acyl-Co-A, which becomes the most oxidized during the cyclic redox reactions that move C 2 units in form of acetyl-Co-A from the fatty acyl chain. The beta carbon becomes the new carboxyl end of the shortened(N- fatty acyl-Co-A.
These oxidation steps are strictly analogous to the reaction steps in the Citric Acid Cycle converting Succinyl-Co-A to Oxaloacetate involving an initial oxidation by Acyl Co-A Dehydrogenase enzyme (driven by FAD. Reduction) and hydration by Enol-Co-A Hydratase. The second oxidation is initiated by that is driven by the NAD reduction.
A C2 unit is then released by the Beta-Ketothiolase enzyme to produce acetyl Co-A and a shortened acyl (N2)-Co-A. The later is recycled until the acyl chain is shortened to its acetyl-Co-A end product and finally oxidized by the Citric Acid Cycle Enzymes.
The structure of Coenzyme A or (CoA) includes a reactive thiol group (-SH) that is critical to its role as an (acyl carrier) in a number of metabolic reactions as are mentioned above. Acyl groups like the acyl molecules from Pyruvic acid become Co-valently linked to this thiol group, forming thioesters. Thioesters have a relatively high free energy of hydrolysis, thus they have a high acyl group transfer potential, donating their acyl groups to a variety of acceptor molecules. The acyl group attached to Coenzyme A is considered as activated for group transfer. Coenzyme A contains Beta- Mercaptoethylamine with the reactive (thiol group), the vitamin Pantothenic acid and the nucleotide derivative 3- Phosphoadenosine Diphosphate.
In almost all cases, the Thiolate form is reactive. This includes nucleophilic and metal binding (Ionic) reactions. Inactivated thiols have (pKa)- values0f~9.
A free thiol is in a reduced state; the formation of a disulfide bond is 2e- oxidation. Disulfide exchange reactions are representative of the redox involvement of thiol cofactors.
The efficient microscale synthesis of [1-14C] propional –CoA from commercially available sodium [-14] propionate using 1,1’ carbonyldiimidazole in yields of nearly 70% has been reported recently for the first time. A substantial improvement in the process for making [1- 14 C] acetyl CoA from sodium [1- 14C] acetate was also achieved. Reported were yields of greater than 90% were consistently obtained for the later synthesis. The salt free CoA thioesters were obtained in homogenous form by reverse– phase HPLC. The products were judged to be pure by 1HMR analysis; neither iso- CoA analogs nor contaminants frequently found in commercial samples could be detected. The samples of Acetyl- and Propional- CoA were shown to be radiochemically pure by HPLC and analysis of the products of incubations with Acetyl- and Propionyl –CoA Carboxylase. This highly efficient synthesis being a very cost effective method of preparation of radiolabled CoA thioesters and can easily be adapted to future production of any other CoA analogs. The synthetic forms of acetyl Coenzyme A are available from SIGMA ALDRICH, MORAVEK BIOCHEMICALS, BOEHRINGER- MANNHEIM, and PERKIN ELMER Life Sciences, Inc. just to name a few. They have been successfully used in their purified form for the synthesis of such pharmaceutical anticancer drugs such as Taxol, and some of the major antibiotics. .
Biovailability, distribution and metabolism of the synthetic compounds of CoA
Scientific studies using synthetic chemical compounds of CoA in isolated rat intestine indicated that orally administered CoA was hydrolyzed to Pantothenic acid within the intestinal lumen via the formation of Dephospho- CoA , Phosphopantetheine and Pantetheine to Pantethine and finally Pantothenic Acid, but not the actual CoA molecule (Shibata et al., 1983). Pantetheinase, an enzyme which can hydrolyze Pantetheine and Pantethine, has been identified in rat intestinal luminal cells (Ono et al., 1974; Shibata et al., 1983; Wittwer et al., 1985). Pantetheine, formed by the stepwise breakdown of CoA, is hydrolyzed to cystamine and Pantothenate, which is excreted in the urine (Whittwer et al., 1983). Although Pantothenic Acid may be absorbed by passive diffusion (the predominant process at high intraluminal Pantothenate concentrations), a saturable, sodium -depended, active transport mechanism has also been described (Fenstermacher & Rose, 1986; Stein & Diamonds, 1989). Further studies indicated that the kinetics of this active intestinal transport process for Pantothenate were not affected by different dietary intake levels of the vitamin form (Stein & Diamonds, 1989).
The above radiolabeled synthetic compounds had the following warnings: Caution: not for use in humans or clinical diagnosis. These products were intended for investigational, testing purposes, or for manufacturing use only. They are pharmaceutically unrefined and not intended for use in humans. Further stability and storage recommendations were: rate of decomposition is approximately 0.1-0 to.0 5% month for the first six months after purification when stored at –20*C.
Abiko Y.; Metabolism of Coenzyme-A; New York Academic Press, Third Edition 1975; 7:1-25.
Annous, K. F. & Song, W. 0.; Pantothenic Acid Uptake and Metabolism By the Red Blood Cell; Journal of Nutrition 1995; 125: 2586-2593.
Binaghi, p., Cellina, G., Lo Cicero, G., Bruschi, F., & Penotti, M.; Evaluation of the Cholesterol-lowering effectiveness of pantethine in Perimenopausal Age; Minerva Med. June 1990; 81: 6, 475-9.
Downing, D. T. & Strauss L. S.; Synthesis and Composition of Surface Lipids of Human Skin 1974; 62.228- 244.
Dupre, A., Albarel, N., Bonofe, J. L., Christol, B., & Lassere, J.; Vitamin B-5; Cutis 1979: 24: 210- 2111979; 24: 210-211.
Eisenstein, P. & Scheiner, S. M. Ph.D.; Overcoming the Pain of Inflammatory Arthritis; Avery Publishing Group 1997.
European Journal of Applied Physiology and Occupational Physiology 1998; Abstract, Volume 77,Issue 6, pages 486-491; Physiological and Performance Responses to Supplementation With Thiamin and Pantothenic Acid Derivatives.
Gaddi, A., Descovich, G. C., Noseda, G., et al; Controlled Evaluation Hyperlipoproteinemia 1984; 50: 73- 83.
Greenberg, D. M.; Metabolism of Sulfur Compounds, Metabolic Pathways; New York Academic Press, Third Edition 1975; 7:1-25.
Grenville, G. D. & Tubbs, P. K.; The Catabolism of Long-Chain Fatty Acids in Mammalian Tissues; Essays in Biochemistry 1969; 4-155-212.
Hendler, S. S. M.D., Ph.D.;The Doctor’s Vitamin and Mineral Encyclopedia; Simon & Schuster, 1990.
Komar V.I; The Use of Pantothenic Acid Preparations in Treating Patients With Viral Hepatitis A; TerArkh 1991; 63: 11, 58-60.
Krebs, H. A.; The Regulation of Release of Ketone Bodies By the Liver; Advanced Enzyme Reaction 1966; 4:339-354.
Kunz, J. R. M., M.D.; The American Medical Association, Family Medical Guide; Random House Inc.; l982.
Leung, L. H., M.D.; Pantothenic Acid as a Weight Reducing Agent: Fasting Without Hunger, Weakness and Ketosis; Medical Hypothesis 1995; 44, 403, 405.
Leung, L. H., M.D.; Pantothenic Acid Deficiency as the Pathogenesis of Acne Vulgaris; Medical Hypothesis 1995; 44, 490, 492.
Lieberman, C. & Bruning, N.; Pantothenic Acid; Chapter 17, The Real Vitamin and Mineral Book; Avery Publishing Group 1997; 113-115.
Life Extension Foundation; Anti-Aging Therapies; http://www.1ef.org; December 31, 1998.
Masoro, E. J.; Lipids and Lipid Metabolism; Annual Review of Physiology 1977; 39-301-21.
Baggot, P.J., Kalamarides, J.A., Shoemaker, J.D. (1999). Valproate-induced biochemical abnormalities in pregnancy corrected by vitamins: a case report. Epilepsia, 40, 512-515.
Baker, H., Frank, 0., Thomson, A.D., Feingold, 5. (1969). Vitamin distribution in red blood cells, plasma and other body fluids. Am. J. Chin. Nutr., 22, 1469-1475.
Barbarat, B., Podevin, R.A. (1986). Pantothenate-sodium cotransport in renal brush- border membranes. J. Biol. Chem., 261, 14455-14460.
Barboriak, J.J., Krehl, W.A. (1957). Effect of ascorbic acid in pantothenic acid deficiency. J. Nutr., 63, 601-609.
Barton-Wright, E.C., Elliott, W.A. (1963). The pantothenic acid metabolism of rheumatoid arthritis. Lancet, Oct. 26, 862-863.
Beinlich, C.J., Naumovitz, R.D., Song, W.O., Neely, J.R. (1990). Myocardial metabolism of pantothenic acid in chronically diabetic rats. J. Mol. Cell. Cardiol., 22, 323-332.
Bender, D.A., Bender, A.E. (1997). Nutrition: a reference handbook. Oxford University Press Oxford, UK.
Bennett, G.D., Ridge, L., Finnell, R.H. (1998). Folate, vitamin B12, inositol or pantothenic acid supplementation exacerbates the frequency of vaiproic acid induced neural tube defects. Toxicologist, 42(1-S), 262 (Abstract).
van den Berg, H. (1997). Bioavailabiity of pantothenic acid. Eur. J. Clin. Nutr., 51, S62-S63.
Brenner, A. (1982). The effects of megadoses of selected B complex vitamins on children with hyperkinesis: controlled studies with long-term follow-up. J. Learn. Disabil., 15, 258-264.
Chatterjee, N.S., Kumar, C.K., Ortiz, A. et al. (1999). Molecular mechanism of the intestinal biotin transport process. Am. J. Physiol., 277, C605-C6 13.
Cochrane, T., Leslie, G. (1952). The treatment of lupus erythematosus with calcium pantothenate and panthenol. J. Invest. Dermat., 18, 365-367.
Department of Health (1991). Pantothenic acid. In: Dietary reference values for food, energy and nutrients for the United Kingdom: Report of the panel on dietary reference values of the committee on medical aspects of food policy. HMSO, London, pp. 113-115.
Eisenstein, P., Schemer, S.A. (1997). Overcoming the pain of inflammatory arthritis: the pain-free promise of pantothenic acid. Avery Publishing Group, Garden City Park, New York.
Eissenstat, B.R., Wyse, B.W., Hansen, R..G. (1986). Pantothenic acid status of adolescents. Am. J. Chin. Nutr., 44, 931-937.
Even, P.C., Decrouy, A., Chinet A. (1994). Defective regulation of energy metabolism in mdx-mouse skeletal muscles. Biochem., J., 304, 649-654.
Everson, G., Northrop, L., Chung, N.Y., Getty, R. (1954). Effect of ascorbic acid on rats deprived of pantothenic acid during pregnancy. J. Nutr., 54, 305-311.
Fenstermacher, D.K., Rose, R.C. (1986). Absorption of pantothenic acid in rat and chick intestine. Am. J. Physiol., 250, G155-G160.
Food and Nutrition Board - Institute of Medicine. (2000). Dietary reference intakes. Thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academy Press, Washington DC.
Fox, H.M. (1984). In: Handbook of Vitamins: Nutritional, Biochemical and Clinical Aspects, Machim, L.J. (ed.), Marcel Dekker, NY, pp. 437-457.
Fry, P.C., Fox, H.M., Tao, H.G. (1976). Metabolic response to a pantothenic acid deficient diet in humans. J. Nutr. Sci. Vitaminol. (Tokyo), 22, 339-346.
General Practitioner Research Group (1980). Calcium pantothenate in arthritic conditions. A report from the General Practitioner Research Group. Practitioner, 224, 208-211.
Glusman, M. (1947). The syndrome of "burning feet" (nutritional melalgia) as a manifestation of nutritional deficiency. Am. J. Med., 3, 211-223.
Goldman, L. (1948). Treatment of subacute and chronic discoid lupus erythematosus with intensive calcium pantothenate therapy. J. Invest. Dermat., 11, 95.
Goldman, L. (1950). Intensive panthenol therapy of lupus erythematosus. J. Invest. Dermat., 15, 291-293.
Grafton, T.F., Dial, S.L., Hansen, D.K. (1997). Lack of amelioration of valproic acid- induced embryotoxicity by pantothenic acid in vitro. Teratology, 55, 58 (ABSTRACT).
Grassl, S.M. (1992). Human placental brush-border membrane Na+-pantothenate cotransport. J. Biol. Chem., 267, 22902-22906.
Gregory, J.R., Foster, K., Tyler, H., Wiseman, M. (1990). The Dietary and Nutritional Survey of British Adults, HMSO, London.
Haslam, R.H., Dalby, J.T., Rademaker, A.W. (1984). Effects of megavitamin therapy on children with attention deficit disorders. Pediatrics, 74, 103-111.
Haslock, D.I., Wright, V. (1971). Pantothenic acid in the treatment of osteoarthrosis. Rheumatology and Physical Medicine, 11, 10-13.
Hatano, M., Hodges, R.E., Evans, T.C. et al. (1967). Urinary excretion of pantothenic acid by diabetic patients and by alloxan-diabetic rats. Am. J. Clin. Nutr., 20, 960-967. Not got.
Hodges, R.E., Ohison, M.A., Bean, W.B. (1958). Pantothenic acid deficiency in man. J. Clin. Invest., 37, 1642-1657.
Hodges, R.E., Bean, W.B., Ohison, M.A., Bleiler, R. (1959). Human pantothenic acid deficiency produced by omega-methyl pantothenic acid. J. Clin. Invest., 38, 1421- 1425.
Johnston, L., Vaughan, L., Fox, H.M. (1981). Pantothenic acid content of human milk. Am. J. Clin. Nutr., 34, 2205-2209.
Kapp, A., Zeck-Kapp, G. (1991). Effect of Ca-pantothenate on human granulocyte oxidative metabolism. Allerg. Immunol., 37, 145-150.
Kimura, S., Furukawa, Y., Wakasugi, J. et al. (1980). Antagonism of L(-)pantothenic acid on lipid metabolism in animals. J. Nutr. Sci. Vitaminol. (Tokyo), 26, 113-117.
Koyanagi, T., Hareyama, S., Kikuchi, R. et al. (1969). Effect of administration of thiamine, riboflavin, ascorbic acid and vitamin A to students on their pantothenic acid contents in serum and urine. Tohoku J. Exp. Med., 98, 357-362.
Lacroix, B., Didier, E., Grenier, J.F. (1988). Role of pantothenic and ascorbic acid in wound healing processes: in vitro study on fibroblasts. Int. J. Vitam. Nutr. Res., 58, 407413.
Latymer, E.A., Coates, M.E. (1981). The effects of high dietary supplements of copper sulphate on pantothenic acid metabolism in the chick. Br. J. Nutr., 45, 431- 439.
Lewis, C.M., King, J.C. (1980). Effect of oral contraceptive agents on thiamin, riboflavin, and pantothenic acid status in young women. Am. J. Cliii Nutr., 33, 832- 838.
Litoff, D., Scherzer, H., Harrison, J. (1985). Effects of pantothenic acid supplementation on human exercise. Med. Sci. Sport. Exerc., 17 [Suppl.], 287.
Lopaschuk, G.D., Michalak, M., Tsang, H. (1987). Regulation of pantothenic acid transport in the heart. Involvement of a Na+-cotransport system. J. Biol. Chem., 262, 3615-3619.
Luecke, R.W., Hoefer, J.A., Thorp, F. Jr. (1952). The relationship of protein to pantothenic acid and vitamin B12 in the growing pig. J. Anim. Sci., 11, 23 8-243.
Moiseenok, A.G., Komar, V.1., Khomich, T.I. et al. (2000). Pantothenic acid in maintaining thiol and immune homeostasis. Biofactors, 11, 53-55.
Nagiel-Ostaszewski, I., Lau-Cam, C.A. (1990). Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat. Res. Commun. Chem. Pathol. Pharmacol., 67, 289-292.
Nelson, M.M., Evans, H.M. (1945). Sparing action of protein on the pantothenic acid requirement of the rat. Proc. Soc. Exp. Biol. Med., 60, 319-320.
Nice, C., Reeves, A.G., Brinck-Johnsen, T., Noll, W. (1984). The effects of pantothenic acid on human exercise capacity. J. Sports Med. Phys. Fitness, 24, 26-29.
Okuda, K., McCollum, E.B., Hsu, J.M., Chow, B.F. (1962). Utilization of vitamin B12 by rats with pantothenic acid deficiency. Proc. Soc. Exp. Biol. Med., 111, 300-304.
Ono, S., Kameda, K., Abiko, Y. (1974). Metabolism of pantetheine in the rat. J. Nutr. Sci. Vitaminol., 20, 203-213.
OTC (2000). OTC Directory 2000-2001, Proprietary Association of Great Britain.
Otsuka, M., Akiba, T., Okita, Y. et al. (1990). Lactic acidosis with hypoglycemia and hyperammonemia observed in two uremic patients during calcium hop antenate treatment. Jpn. J. Med., 29, 324-328.
Palekar, A. (2000). Effect of pantothenic acid on hippurate formation in sodium benzoate-treated HepG2 cells. Pediatr. Res., 48, 357-359.
Pelton, RB., Williams, R.J. (1958). Effect of pantothenic acid on the longevity of mice. Proc. Soc. Exp. Biol. Med., 99, 632-633.
Plesofsky-Vig, N. (1999). Pantothenic acid. In: Modern Nutrition in Health and Disease, 9th ed., Shils, M.E., Qlson, J.A., Shike, M., Ross, A.C. (eds), Williams & Wilkins, Baltimore, pp. 423-432.
Prasad, P.D., Ramamoorthy, S., Leibach, F.H., Ganapathy, V. (1997). Characterisation of a sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin and lipoate in human placental choriocarcinoma cells.
Prasad, P.D., Srinivas, S.R., Wang, H. et at. (1999). Electrogenic nature of rat sodium-dependent multivitamin transport. Biochem. Biophys. Res. Comm., 270, 836-840.
Prival, M.J., Simmon, V.F., Mortelmans, K.E. (1991). Bacterial mutagenicity testing of 49 food ingredients gives very few positive results. Mutat. Res., 260, 321-329.
Pudelkewicz, C., Roderuck, C. (1960). Pantothenic acid deficiency in the young guinea pig. J. Nutr., 70, 348-352.
Ralli, E.P. (1952). The effect of certain nutritional factors on the reactions produced by acute stress in human subjects. National Vitamin Foundation Nutrition Symposium, 5, 78-103.
Reibel, D.K., Wyse, B.W., Berkich, D.A. et at. (1981). Effects of diabetes and fasting on pantothenic acid metabolism in rats. Am. J. Physiol., 240, E597-E601.
Robishaw, J.D., Berkich, D., Neely, J.R. (1982). Rate-limiting step and control of coenzyme A synthesis in cardiac muscle. J. Biol. Chem., 257, 10967-10972.
Robinson, F.A. (1966). The vitamin co-factors of enzyme systems. Pergamon Press, Oxford, pp. 406-486.
Said, H.M., Ortiz, A., McCloud, E. et at. (1998). Biotin uptake by human colonic epithelial NCM46O cells: a carrier-mediated process shared with pantothenic acid.
Sato, M., Sitirota, M., Nagao, T. (1995). Pantothenic acid decreases valproic acid- induced neural tube defects in mice (I). Teratology, 52, 143-148.
Schroeder, H.A. (1971). Losses of vitamins and trace minerals resulting from processing and preservation of foods. Am. J. Chin. Nutr., 24, 562-573.
Sewell, R.F., Price, D.G., Thomas, M.C. (1962). Pantothenic acid requirement of the pig as influenced by dietary fat. Fed. Proc., 21, 468.
Shibata, K., Gross, C.J., Henderson, L.M. (1983). Hydrolysis and absorption of pantothenate and its coenzymes in the rat small intestine. J. Nutr., 113, 2107-2115.
Shrimpton, D (1995). Essential Nutrients in Supplements. European Federation of Associations of Health Product Manufacturers.
Sivak, A., Tu, A.S. (1980). Cell culture tumor promotion experiments with saccharin, phorbol myristate acetate and several common food materials. Cancer Lett., 10, 27-32.
Slyshenkov, V.5., Omelyanchik, S.N., Moiseenok, A.G. et at. (1998). Pantothenol protects rats against some deleterious effects of gamma radiation. Free Radic. Biol. Med., 24, 894-899.
Song, W.O., Wyse, B.W., Hansen, R.G. (1985). Pantothenic acid status of pregnant and lactating women. J. Am. Diet. Assoc., 85, 192-198.
Sonmez, A., Lurie, D., Chuong, C.J. (2000). Effects of pantothenic acid on postoperative adhesion formation in a rat uterine horn model. Arch. Gynecol. Obstet., 263, 164-167.
Spector, R., Mock, D. (1987). Biotin transport through the blood-brain barrier. J. Neurochem., 48, 400-404.
Srinivasan, V., Christensen, N., Wyse, B.W., Hansen, R.G. (1981). Pantothenic acid nutritional status in the elderly-institutionalized and non-institutionalized. Am. J. Chin. Nutr., 34, 1736-1742.
Stein, E.D., Diamonds, J.M. (1989). Do dietary levels of pantothenic acid regulate its intestinal uptake in mice? J. Nutr., 119, 1973-1983.
Tahiliani, A.G., Beinlich, C.H. (1991). Pantothenic acid in health and disease. Vitam. Horm., 46, 165-228.
Tao, H.G., Fox, H.M. (1976). Protein-pantothenic acid interrelationships in growing rats. Nutr. Rep. Int., 14, 97-106.
Tair, J.B., Tamura, T., Stokstad, E.L. (1981). Availability of vitamin B6 and pantothenate in an average American diet in man. Am. J. Clin. Nutr., 1328-1337.
Unna, K. Greslin, J.G. (1940). Toxicity of pantothenic acid. Proc. Soc. Exp. Biol. Med., 45, 311-312.
Unna, K., Greslin, J.G. (1941). Studies on the toxicity and pharmacology of pantothenic acid. J. Pharmacol. Exp. Ther., 73, 85-90.
Vas, A., Gachalyi, B., Kaldor, A. (1990). Pantothenic acid, acute ethanol consumption and sulphadimidine acetylation. Int. J. Chin. Pharrnacol. Ther. Toxicol., 28, 111-114.
Vaxman, F., Olender, S., Lambert, A. et at. (1995). Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. Eur. Surg. Res., 27, 158-166.
Vaxman, F., Olender, S., Lambert, A. et at. (1996). Can the wound healing process be improved by vitamin supplementation? Experimental study on humans. Eur. Surg. Res., 28, 306-314.
Walsh, J.H., Wyse, B.W., Hansen R.G. (1981). Pantothenic acid content of 75 processed and cooked foods. J. Am. Diet. Assoc., 78, 140-144.
Wang, H., Huang, W., Fei, Y.J. et at. (1999). Human placental Na±-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. J. Biol. Chem., 274, 14875-14883.
Webster, M.J. (1998). Physiological and performance responses to supplementation with thiamin and pantothenic acid derivatives. Eur. J. Appl. Physiol. Occup. Physiol., 77, 486-491.
Welsh, A.L. (1952). Lupus erythematosus: treatment by combined use of massive amounts of calcium pantothenate or panthenol with synthetic vitamin E. Arch. Dermat., Syph., 65, 137-148.
Welsh, A.L. (1954). Lupus erythematosus: treatment by combined use of massive amounts of pantothenic acid and vitamin E. Archives of Dennatology, 70, 181-198.
Wittwer, C.T., Gahi, W.A., Butler, J. deB. et al. (1985). Metabolism of pantethine in cystinosis. J. Chin. Invest., 76, 1665-1672.
Wittwer, C.T., Burkhard, D., Ririe, K. (1983). Purification and properties of a pantetheine-hydrolyzing enzyme from pig kidney. J. Biol. Chem., 257, 9733-9738.
Microsoft Bookshelf, 1996-1997 Edition: The American Heritage Dictionary, Third Edition; The Concise Columbia Encyclopedia, Third Edition; The World Almanac and Book of Facts; Microsoft Bookshelf Internet Directory 96-97.
Moertel, C. G., Fleming, T. R., Coregan, E. T., Rubin, J., & O’Connell M.; England Med. 1985; 312: 137- 141.
Pearson, D. .& Shaw, S.; Life Extension, A practical Scientific Approach; Warner Books Inc.; June 1983. Ralli, E. P. & Dumm, M. E.; Relation of Pantothenic Acid Load on Adrenal Cortical Function; Vitam Horn 1953; 11: 133-158.
Robishaw, J. D. & Neely, J. R.; Coenzyme A Metabolism; American Joumal of Physiology 1985; 248: El- E9.
Sturnpf, P. K.; Metabolism of Fatty Acids; Annual Review of Biochemistry 1969; 38-159-212.
Zabel J.; Serum Testosterone Concentration in Boys With Acne; Przegl. Dermatology 1981; 68, 189.
Knight, G. D., Ph.D.; A Waist is a terrible thing to mind; Medical Hypothesis 1998.
Dottori, S., Molajoni, F., and Ramsay, R.R. (1992)1 Biol. Chem. 267, 12673-12681
Ardalni, A., Denisova, N., Vinnani, A., Avrova, N., Federici; G., and Arnigoni, M. E. (1994)J Neurochem. 62, 1530-1538
Nikolacs, S., George, A., Telemachos, T., Maria, S., Yannis, M., and Konstantinos, M. (2000) Ren Fail. 22, 73-80
Andrieu, A. N., Jaffrezou, J. P., Hatem, S., Laurent, G., Levade, T., and Mercadier, J. J. (1999)FASEB1 13, 1501-1510
Mutoinba, M. C., Yuan, H., Konyavko, M., Adachi, S., Yakoyama, C. B., Esser, V., McGarry, J. D., Babior, B. M., and Gottlieb, R. A. (2000) Febs Letters 478, 19-25
Paumen, M. B., Ishida, Y., Muramatsu, M., Yamamoto, M., and Honjo, T. (1997)J. Biol. Chem. 272, 3324-3329
Chalmers, R. A., Roe, C. R, Tracey, B. M., Stacey, R. E., Hoppel, C. L., and Millingron, D. S. (1983) Bochem. Soc. Trans. 11,724-5
Siliprandi, N., Siliprandi, D., and Ciman, M. (1965)Biochem. J. 96, 777-780
White, H. L. and Scates, P.W. (1990) Neurochem.Res. 15,597-601
Pettegrew, J. W., Klunk, W. E., Panchalingam, K., Kanfer, J. N., and McClure, P.. J. (1995) Neurobiot. Aging 16, 1-4
Fedele, D. and Giugliano, D. (1997) Drugs 54, 414-421
Di Lisa, F., Menab6, R., Barbato, R., and Siliprandi, N. (1994) Am. 1 Physiot. 267, H455- 61
Packer, L., Valenza, M., Serbinova, E., Starke Reed, P., Frost, K., and Kagan, V. (1991)Arch. 288,533-537
Sassen, L. M., Bezstarosti, K., Van Der Giessen, W. J., Lamers, J. M. J., and Verdouw, Siliprandi, N., and Mortimore, G. (1996) .1 Biol. Chem. 267, 22066-22072