KINS 7338 Micronutrient Metabolism in Sports Nutrition

1. KINS 7338Micronutrient Metabolism in Sports Nutrition Pantothenic Acid Alaine Mills

2. History • Pantothenic Acid was first isolated in 1931 by R.J. Williams • Structure was determined in 1939 • Essentially was not discovered, however, until 1954. • Also known as “Pantothenate” • The vitamin was once called vitamin B5

3. Structure • Consists of: • β- Alanine • Pantoic Acid • Joined by a peptide bond/amide linkage • *See structure (figure 9.17) on page 339 • Commonly found bound to Coenzyme A • Structure (figure 9.18) on page 340

4. Chemistry & Activity • Pantothenic acid is not considered very stable • Easily destroyed by heat • Cooking • Destroyed in acidic or alkaline conditions • Stable in a neutral solution only • In supplements it is usually included as calcium pantothenate • More stable

5. Body Distribution • Pantothenic acid along with 4’-phosphopantothenate and pantetheine may be found in the body’s cells • Free Pantothenic acid is found in plasma, however, higher concentrations are found intracellularly • Mainly in RBC’s • Most ingested pantothenic acid is used to synthesize or resynthesize CoA • Found in fairly high concentrations in the • Liver • Adrenal gland • Kidney • Brain • Heart

6. Biomechanical Mechanism • Functions in the body as a component of CoA and 4’- phosphopantetheine • The synthesis of these from pantothenic acid requires pantothenic acid, the amino acid cysteine, and ATP • Steps • Pantothenic acid → 4’- phosphopantetheine • Via pantothenate kinase • ATP and Mg2+ required • To form Coenzyme A from 4’- phosphopantetheine, a peptide bond is formed between the carboxyl group, and the amino group of cysteine • Requires ATP

7. Biomechanical Mechanism • The synthesis of CoA is inhibited by acetyl CoA, malonyl CoA, and propionylCoA • Pantothenic acid as 4’- phosphopantethine also functions as the prosthetic group for acyl carrier protein (ACP) • Carriers or transporters of acetyl or acyl groups, as needed for various cellular reactions • Forms Thio esters with carboxylic acid groups

8. Digestion, Absorption & Transport • 85% of the pantothenic acid found in foods is bound to CoA. • During digestion, CoA is hydrolyzed in the lumen to pantothenic acid • Via phosphatases and pyrophosphatases • Free pantothenic acid can then be absorbed (mainly in the jejunum) • High concentrations by passive diffusion • Low concentrations via a Na+ dependent active multivitamin transporter (SMVT) • This carrier is also shared with biotin and lipoic acid

9. Digestion, Absorption & Transport • 40 to 61% of pantothenic acid is absorbed • From the intestinal cell, it will enter the portal blood for transportto body cells • Pantothenic acid is found free in plasma, however, higher concentrations are found intracellularly, mainly in RBC’s • Uptake by tissues • Heart, liver, muscle, and brain • Via Na+ dependent active transport • Other tissues • Via facilitated diffusion • Most Pantothenic acid is used to synthesize or resynthesize CoA • Found in fairly high concentrations in the liver, adrenal gland, kidney, brain, and heart

10. Functions • Functions in the body as a component of CoA and 4’- phosphopantetheine. • As a part of these, pantothenic acid participates extensively in nutrient metabolism • Degredationrxns resulting in energy production • Synthetic reactions for the production of many compounds • Thus, it is important for the maintenance and repair of all cells and tissues • CoA also acetylates (donation of the long chain-fatty acids or acetate) nutrients including sugars and proteins, and some drugs • Acetylation of some enzymes results in either activation or inactivation

11. Functions • The metabolism of CHO, lipids, and proteins relies on varying degrees of CoA. • Ex: Pyruvate – Acetyl CoA • Acetyl- CoA is the common compound formed from the three-energy producing nutrients • Requires pantothenic acid • Pantothenic acid joins the B vitamins thiamin, riboflavin, and niacin in the following: • Decarboxylation of pyruvate • Decarboxylation of α-ketoglutarate- Succinyl- CoA • Used with Glycine to synthesize heme

12. Functions • In lipid metabolism, CoA is important in the synthesis of • Cholesterol • Bile salts • Ketone bodies • Fatty Acids • Steriod hormones

13. Functions • Pantothenic acid as 4’- phosphopantetheine also functions as the prosthetic group for acyl carrier protein (ACP). • Acts as the acyl carrier in the synthesis of fatty acids • Is a necessary component of the fatty acid synthase complex • The vitamin also appears to accelerate normal healing process following surgery • Exact mechanism is still unclear

14. Excretion • Does not appear to undergo metabolism prior to excretion • Excreted intact in the urine • Small amounts in the feces • No metabolites of the vitamin have been identified • Urinary excretion of the vitamin usually ranges from about 2 to 7 mg/day

15. Deficiency • “Burning Feet Syndrome” • Present in virtually ALL plant and animal foods, so a deficiency is highly unlikely • Deficiency is thought to occur more often in conjunction with multiple nutrient deficiencies, for example malnutrition • Syndrome can be corrected with calcium pantothenate administration

16. Deficiency Symptoms • Characterized by: • Numbness of toes and burning sensation in the feet • Vomiting, fatigue, weakness, restlessness, and irritability • Conditions that may increase the need for the vitamin • Alcoholism • DM • Inflammatory bowel diseases

17. Toxicity • Toxicity has not been reported to date in humans • Intakes of about 10g pantothenate as calcium pantothenate daily for up to 6 weeks have resulted in no problems

18. Toxicity Symptoms • Intakes of about 15 to 20g daily have been associated with: • Mild intestinal distress • Diarrhea

19. Food Sources • The greek word pantosmeans “everywhere” • Pantothenic acid is found widely distributed in nature • Present in virtually ALL plant and animal foods • Good sources: Meats (particularly liver), egg yolk, legumes, whole-grain cereals, potatoes, mushrooms, broccoli, and avocados • Most adults consume about 4 to 7 mg pantothenic acid per day

20. Requirements • The AI recommendation for adults age 19 years and older • 5mg/day • 6mg/day for pregnancy • 7mg/day for lactation

21. Assessment • Blood pantothenic acid concentrations • <100 mg/dl reflects low dietary pantothenate intakes • Urinary pantothenate excretion is considered to be a better indicator • <1mg/day considered indicative of poor status

22. Recent Research • High fat diets and pantothenic acid levels • Pantothenic acid is heavily involved in fatty acid metabolism • High fat diets have shown to affect liver CoA levels in rats • A study was conducted in 2010 • Purpose: to determine how a high fat diet affects Pantothenic acid metabolism

23. High Fat Diets and Pantothenic Acid • Rats were fed either a 5% or 30% fat diet with limited amounts of pantothenic acid • Ad libitum • 28 days • Urine Analysis was conducted on the last day

24. High Fat Diets and Pantothenic Acid • Results • Fat content of the diet affected pantothenic acid metabolism • The plasma, liver, and adrenal pantothenic acid levels in the rats fed the 30% fat diet were significantly lower than with the 5% fat diet

25. High Fat Diets and Pantothenic Acid • Discussion • The high fat diet could inhibit Pantothenic acid absorption in the intestines • The pantothenic acid is being used for fatty acid breakdown and synthesis • An increased reliance on fat for fuel alters pantothenic acid metabolism

26. References • Gropper, S., Smith, J., & Groff, J. (2009). Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth, Cengage Learning. • Yoshida, E., Tsutomu, F., Ohtsubo, M., & Shibata, K. (2010). High fat diet lowers the nutritional status indicators of pantothenic acid in weaning rats. Biosci. Biotechno. Bichem., 74(8), 1691- 1693.