KINS 7338Micronutrient Metabolism in Sports Nutrition

Pantothenic AcidAlaine Mills

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

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

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

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

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

Biomechanical Mechanism • The synthesis of CoA is inhibited by acetyl CoA, malonyl CoA,

and propionyl CoA• 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

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

Digestion, Absorption & Transport

• 40 to 61% of pantothenic acid is absorbed• From the intestinal cell, it will enter the portal blood for

transport to 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

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• Degredation rxns 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

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

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

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

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

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

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

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

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

Food Sources• The greek word pantos means “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

Requirements • The AI recommendation for adults age 19 years and older• 5mg/day

• 6mg/day for pregnancy• 7mg/day for lactation

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

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

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

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

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

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.