Pantothenic acid

Pantothenic acid
Names
Preferred IUPAC name
3-[(2R)-2,4-Dihydroxy-3,3-dimethylbutanamido]propanoic acid
Systematic IUPAC name
3-[(2R)-(2,4-Dihydroxy-3,3-dimethylbutanoyl)amino]propanoic acid
Identifiers
3DMet B00193
1727062, 1727064 (R)
599-54-2 
79-83-4 (R) 
ChEBI CHEBI:7916 
ChEMBL ChEMBL1594 Yes
ChemSpider 963 
6361 (R) 
4677898 (S) 
DrugBank DB01783 Yes
EC-number 209-965-4
Jmol-3D images Image
Image

(R)
Image (S)

KEGG D07413 Yes
MeSH Pantothenic+Acid
PubChem 988
6613 (R)
5748353 (S)
RTECS number RU4729000
UNII 19F5HK2737 
Properties
Molecular formula
 C9H17NO5
Molar mass 219.23 g·mol−1
Appearance Yellow oil
Colorless crystals (Ca2+ salt)
Odor Odorless
Density 1.266 g/cm3
1.32 g/cm3 (Ca2+ salt)[1]
Melting point 183.83 °C (362.89 °F; 456.98 K)
196–200 °C (385–392 °F; 469–473 K)
decomposes (Ca2+ salt)[1][2][3]
138 °C (280 °F; 411 K)
decomposes (Ca2+ salt, monohydrate)[4]
Very soluble[5]
2.11 g/mL (Ca2+ salt)[1]
Solubility Very soluble in C6H6, ether[5]
Ca2+ salt:
Slightly soluble in alcohol, CHCl3[2]
log P −1.416[6]
Acidity (pKa) 4.41[3]
Basicity (pKb) 9.698
+37.5°
+24.3° (Ca2+ salt)[3]
Hazards
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
1
2
0
Flash point 287.3 °C (549.1 °F; 560.5 K)[4]
> 10 mg/g (Ca2+ salt)[2]
Related compounds
Related alkanoic acids
 Arginine
Hopantenic acid
4-(γ-Glutamylamino)butanoic acid
Related compounds
 Panthenol
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
  verify (what is: Yes/?)

Pantothenic acid, also called pantothenate or vitamin B5 (a B vitamin), is a water-soluble vitamin. For many animals, pantothenic acid is an essential nutrient. Animals require pantothenic acid to synthesize coenzyme-A (CoA), as well as to synthesize and metabolize proteins, carbohydrates, and fats.

Pantothenic acid is the amide between pantoic acid and β-alanine. Its name derives from the Greek pantothen (πάντοθεν), meaning "from everywhere", and small quantities of pantothenic acid are found in nearly every food, with high amounts in avocado, whole-grain cereals, legumes, eggs, meat, royal jelly, and yogurt.[7] It is commonly found as its alcohol analog, the provitamin panthenol (pantothenol), and as calcium pantothenate. Pantothenic acid is an ingredient in some hair and skin care products.[8]

Pantothenic acid was discovered by Roger J. Williams in 1933.[9]

Biological role

Only the dextrorotatory (D) isomer of pantothenic acid possesses biologic activity.[10] The levorotatory (L) form may antagonize the effects of the dextrorotatory isomer.[11]

Pantothenic acid is used in the synthesis of coenzyme A (CoA). Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell.[12] CoA is important in energy metabolism for pyruvate to enter the tricarboxylic acid cycle (TCA cycle) as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle.[13] CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine.[13] CoA is incidentally also required in the formation of ACP,[14] which is also required for fatty acid synthesis in addition to CoA.[12]

Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively.[15]

Since pantothenic acid participates in a wide array of key biological roles, it is essential to all forms of life.[16] As such, deficiencies in pantothenic acid may have numerous wide-ranging effects, as discussed below.

Sources

Dietary

Small quantities of pantothenic acid are found in most foods.[17] The major food source of pantothenic acid is meat. The concentration found in human muscle is about double that in other animals' muscle.[18] Whole grains are another good source of the vitamin, but milling removes much of the pantothenic acid, as it is found in the outer layers of whole grains.[19] Vegetables, such as avocados and broccoli, also have an abundance.[20] In animal feeds, the most important sources are alfalfa, cereal, condensed fish solutions, peanut meal, molasses, mushrooms, rice, wheat bran, and yeasts. The most significant sources of pantothenic acid in nature are coldwater fish ovaries and royal jelly.[21]:346

Supplementation

The derivative of pantothenic acid, pantothenol (panthenol), is a more stable form of the vitamin and is often used as a source of the vitamin in multivitamin supplements.[21]:347 Another common supplemental form of the vitamin is calcium pantothenate. Calcium pantothenate is often used in dietary supplements because, as a salt, it is more stable than pantothenic acid in the digestive mentation may improve oxygen utilization efficiency and reduce lactic acid accumulation in athletes.[21]

Daily requirement

Pantothenate in the form of 4'phosphopantetheine is considered to be the more active form of the vitamin in the body; however, any derivative must be broken down to pantothenic acid before absorption.[22] 10 mg of calcium pantothenate is equivalent to 9.2 mg of pantothenic acid.

Age group Age Requirements[19]
Infants 0–6 months 1.7 mg
Infants 7–12 months 1.8 mg
Children 1–3 years 2 mg
Children 4–8 years 3 mg
Children 9–13 years 4 mg
Adult men and women 14+ years 5 mg
Pregnant women (vs. 5) 6 mg
Breastfeeding women (vs. 5) 7 mg

Absorption

When found in foods, most pantothenic acid is in the form of CoA or acyl carrier protein (ACP). For the intestinal cells to absorb this vitamin, it must be converted into free pantothenic acid.[22] Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4'-phosphopantetheine.[22] The 4'-phosphopantetheine is then dephosphorylated into pantetheine.[22] Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid.[22]

Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system.[13] At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be absorbed via passive diffusion.[21] As intake increases 10-fold, however, absorption rate decreases to 10%.[13]

Deficiency

Pantothenic acid deficiency is exceptionally rare and has not been thoroughly studied. In the few cases where deficiency has been seen (victims of starvation and limited volunteer trials), nearly all symptoms can be reversed with the return of pantothenic acid.[13]

Symptoms of deficiency are similar to other vitamin B deficiencies. There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue, and apathy.[13] Acetylcholine synthesis is also impaired; therefore, neurological symptoms can also appear in deficiency;[20] they include numbness, paresthesia, and muscle cramps.[20] Deficiency in pantothenic acid can also cause hypoglycemia, or an increased sensitivity to insulin.[13] Insulin receptors are acylated with palmitic acid when they do not want to bind with insulin.[22] Therefore, more insulin will bind to receptors when acylation decreases, causing hypoglycemia.[12] Additional symptoms could include restlessness, malaise, sleep disturbances, nausea, vomiting, and abdominal cramps.[20] In a few rare circumstances, more serious (but reversible) conditions have been seen, such as adrenal insufficiency and hepatic encephalopathy.

One study noted reports of painful burning sensations of the feet in tests conducted on volunteers.[16] Deficiency of pantothenic acid may explain similar sensations reported in malnourished prisoners of war.

Deficiency symptoms in other nonruminant animals include disorders of the nervous, gastrointestinal, and immune systems, reduced growth rate, decreased food intake, skin lesions and changes in hair coat, and alterations in lipid and carbohydrate metabolism.[23]

Toxicity

Toxicity of pantothenic acid is unlikely. In fact, no Tolerable Upper Level Intake (UL) has been established for the vitamin.[22] Large doses of the vitamin, when ingested, have no reported side effects and massive doses (e.g., 10 g/day) may only yield mild intestinal distress, and diarrhea at worst.[13] It has been suggested, however, that high doses of pantothenic acid might worsen panic attacks in those with panic disorder by prolonging the duration until adrenal exhaustion.

There are also no adverse reactions known following parenteral or topical application of the vitamin.[24]

Research

Given pantothenic acid's prevalence among living things and the limited body of studies in deficiency, many uses of pantothenic acid have been the subject of research.

Diabetic ulceration

Foot ulceration is a problem commonly associated with diabetes, which often leads to amputation.[25] A preliminary study completed by Abdelatif, Yakoot and Etmaan indicated that perhaps a royal jelly and panthenol ointment can help cure the ulceration.[25] People with foot ulceration or deep tissue infection in the study had a 96% and 92% success rate of recovery.[25] While these results appear promising, they need to be validated, as this was a pilot study; it was not a randomized, placebo-controlled, double-blind study.[25]

Hypolipidemic effects

Pantothenic acid derivatives, panthenol, phosphopantethine and pantethine, have also been seen to improve the lipid profile in the blood and liver.[26] In this mouse model, they injected 150 mg of the derivative/kg body weight.[26] All three derivatives were able to effectively lower low-density lipoprotein (LDL), as well as triglyceride (TG) levels; panthenol was able to lower total cholesterol, and pantethine was able to lower LDL-cholesterol in the serum.[26] The decrease in LDL is significant, as it is related to a decrease the risk of myocardial infarction and stroke.[13] In the liver, panthenol was the most effective, as it lowered TG, total cholesterol, free cholesterol and cholesterol-ester levels.[26]

Wound healing

A study in 1999 showed pantothenic acid has an effect on wound healing in vitro.[27] Wiemann and Hermann found cell cultures with a concentration of 100 μg/mL calcium D-pantothenate increased migration, and the fibers ran directionally with several layers, whereas the cell cultures without pantothenic acid healed in no orderly motion, and with fewer layers.[27] Cell proliferation or cell multiplication was found to increase with pantothenic acid supplementation.[27] Finally, increased concentrations of two proteins, both of which have yet to be identified, were found in the supplemented culture, but not in the control.[27] Further studies are needed to determine whether these effects will stand in vivo.

Hair care

Mouse models identified skin irritation and loss of hair color as possible results of severe pantothenic acid deficiency.[28] As a result, the cosmetic industry began adding pantothenic acid to various cosmetic products, including shampoo. These products, however, showed no benefits in human trials.[29] Despite this, many cosmetic products still advertise pantothenic acid additives. [30][31][32][33][34][35]

Diabetic peripheral polyneuropathy

Twenty-eight out of 33 patients (84.8%) previously treated with alpha-lipoic acid for peripheral polyneuropathy reported further improvement after combination with pantothenic acid. The theoretical basis for this is that both substances intervene at different sites in pyruvate metabolism and are, thus, more effective than one substance alone. Additional clinical findings indicated diabetic neuropathy may occur in association with a latent prediabetic metabolic disturbance, and that the symptoms of neuropathy can be favorably influenced by the described combination therapy, even in poorly controlled diabetes.[36]

Ruminant nutrition

No dietary requirement for pantothenic acid has been established as synthesis of pantothenic acid by ruminal microorganisms appears to be 20 to 30 times more than dietary amounts. Net microbial synthesis of pantothenic acid in the rumen of steer calves has been estimated to be 2.2 mg/kg of digestible organic matter consumed per day. The degradation of dietary intake of pantothenic acid is considered to be 78 percent. Supplementation of pantothenic acid at 5 to 10 times theoretic requirements did not improve performance of feedlot cattle[37]

See also

References

  1. ↑ 1.0 1.1 1.2 "Scientific Opinion on the safety and efficacy of pantothenic acid (calcium D-pantothenate and D-panthenol) as a feed additive for all animal species based on a dossier submitted by Lohmann Animal Health" (PDF). http://www.efsa.europa.eu''. Parma, Italy: European Food Safety Authority. 2011. Retrieved 2014-09-05.
  2. ↑ 2.0 2.1 2.2 "CALCIUM D-PANTOTHENATE". https://www.chemicalland21.com''. AroKor Holdings Inc. Retrieved 2014-09-05.
  3. ↑ 3.0 3.1 3.2 Leenheer, André P. De; Lambert, Willy E.; Bocxlaer, Jan F. Van, eds. (2000). Modern Chromatographic Analysis Of Vitamins: Revised And Expanded. http://www.dekker.com''. Chromatographic Science 84 (3rd ed.) (Marcel Dekker). p. 533. ISBN 0-203-90962-3.
  4. ↑ 4.0 4.1 "DL-Pantothenic acid calcium salt". http://www.guidechem.com''. Guidechem. Retrieved 2014-09-05.
  5. ↑ 5.0 5.1 Lide, David R., ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0.
  6. ↑ "MSDS of D-pantothenic acid" (PDF). http://www.hmdb.ca''. Human Metabolome Database. Retrieved 2014-09-05.
  7. ↑ "Pantothenic Acid". Linus Pauling Institute at Oregon State University. Micronutrient Information Center. Retrieved 7 November 2010.
  8. ↑ Eastern Washington University. "Soap, Detergent, Cosmetic Ingredients". Retrieved 12 June 2012.
  9. ↑ Richards, Oscar W. (1938). "The Stimulation of Yeast Proliferation By Pantothenic Acid" (PDF). Journal of Biological Chemistry 113 (2): 531–536.
  10. ↑ MedlinePlus. "Pantothenic acid (Vitamin-B5), Dexpanthenol". Natural Standard Research Collaboration. U.S. National Library of Medicine. Last accessed 4 January 2007.
  11. ↑ Kimura S, Furukawa Y, Wakasugi J, Ishihara Y, Nakayama A (1980). "Antagonism of L(-)pantothenic acid on lipid metabolism in animals". J. Nutr. Sci. Vitaminol. 26 (2): 113–7. doi:10.3177/jnsv.26.113. PMID 7400861.
  12. ↑ 12.0 12.1 12.2 Voet, D., Voet, J.G., Pratt, C.W. (2006). Fundamentals of Biochemistry: Life at the Molecular Level, 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc.
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning.
  14. ↑ Sweetman, L. (2005). Pantothenic Acid. Encyclopedia of Dietary Supplements. 1: 517-525.
  15. ↑ Gropper, S. S, Smith, J. L., Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, CA: Wadsworth, Cengage learning
  16. ↑ 16.0 16.1 Jane Higdon, "Pantothenic Acid", Micronutrient Information Center, Linus Pauling Institute, Oregon State University
  17. ↑ "Nutrient Data Products and Services, Nutrient Data : Reports by Single Nutrients". Retrieved 2007-08-12.
  18. ↑ Roger J. Williams. "The Clayton Foundation Biochemical Institute: A Short History". Biochemical Institute at the University of Texas at Austin.
  19. ↑ 19.0 19.1 Dietary Reference Intakes of Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press, 2000 http://books.nap.edu/catalog/6015.html
  20. ↑ 20.0 20.1 20.2 20.3 Otten, J. J., Hellwig, J. P., Meyers, L. D. (2008). Dietary reference intakes: The essential guide to nutrient requirements. Washington, DC: The National Academies Press
  21. ↑ 21.0 21.1 21.2 21.3 Combs, G. F. (2008). The vVitamins: Fundamental Aspects in Nutrition and Health (3rd ed.). Boston: Elsevier. ISBN 978-0-12-183493-7.
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 Trumbo, P. R. (2006). "Pantothenic Acid". In Shils, M. E.; Shike, M.; Ross, A. C.; Caballero, B.; Cousins, R. J. Modern Nutrition in Health and Disease (10th ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 462–467. ISBN 0-7817-4133-5.
  23. ↑ Smith, C. M.; Song, W. O. (1996). "Comparative nutrition of pantothenic acid". Journal of Nutritional Biochemistry 7 (6): 312–321. doi:10.1016/0955-2863(96)00034-4.
  24. ↑ Combs, G. F. Jr. (1998). The Vitamins: Fundamental Aspects in Nutrition and Health (2nd ed.). Ithaca, NY: Elsevier Academic Press. p. 374. ISBN 0-12-183492-1.
  25. ↑ 25.0 25.1 25.2 25.3 Abdelatif, M.; Yakoot, M.; Etmaan, M. (2008). "Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study". Journal of Wound Care 17 (3): 108–110. PMID 18376651.
  26. ↑ 26.0 26.1 26.2 26.3 Naruta, E.; Buko, V. (2001). "Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose". Experimental and Toxologic Pathology 53 (5): 393–398. doi:10.1078/0940-2993-00205. PMID 11817109.
  27. ↑ 27.0 27.1 27.2 27.3 Weimann, B. J.; Hermann, D. (1999). "Studies on wound healing: Effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture". International Journal for Vitamin and Nutrition Research 69 (2): 113–119. doi:10.1024/0300-9831.69.2.113. PMID 10218148.
  28. ↑ Y. M. Kuo, S. J. Hayflick, and J. Gitschier (June 2007). "Deprivation of pantothenic acid elicits a movement disorder and azoospermia in a mouse model of pantothenate kinase-associated neurodegeneration". J Inherit Metab Dis. 30 (3): 310–317. doi:10.1007/s10545-007-0560-8. PMC 2099457. PMID 17429753.
  29. ↑ Linus Pauling Institute. "Micronutrient Information Center – Pantothenic Acid". Retrieved 12 June 2012.
  30. ↑ G. David Novelli (1953). "Metabolic Functions of Pantothenic Acid". Physiol Rev 33 (4): 525–43. PMID 13100068.
  31. ↑ Schalock PC, Storrs FJ, Morrison L. (2000). "Contact urticaria from panthenol in hair conditioner". Contact Dermatitis 43 (4): 223. doi:10.1034/j.1600-0536.2000.043004223.x. PMID 11011922.
  32. ↑ D.W. Woolley (1941). "Identification of the mouse antialopecia factor". J. Biol. Chem. 139 (1): 29–34.
  33. ↑ Shun Ishibashi , Margrit Schwarz , Philip K. Frykman , Joachim Herz and David W. Russell (1996). "Disruption of Cholesterol 7-Hydroxylase Gene in Mice, I. Postnatal lethality reversed by bile acid and vitamin supplementation". J. Biol. Chem. 271 (30): 18017–18023. doi:10.1074/jbc.271.30.18017. PMID 8663429.
  34. ↑ C. Smith, W. Song (1996). "Comparative nutrition of pantothenic acid". The Journal of Nutritional Biochemistry 7 (6): 312–321. doi:10.1016/0955-2863(96)00034-4.
  35. ↑ Paul F. Fenton2, George R. Cowgill, Marie A. Stone and Doris H. Justice (1950). "The Nutrition of the Mouse, VIII. Studies on Pantothenic Acid, Biotin, Inositol and P-Aminobenzoic Acid". Journal of Nutrition 42 (2): 257–269. PMID 14795275.
  36. ↑ Münchener Medizinische Wochenschrift (Germany), 1997, 139/12 (34-37)
  37. ↑ National Research Council. 2001. Nutrient Requirements of Dairy Cattle. 7th rev. ed. Natl. Acad. Sci., Washington, DC.

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