*Vit B5

*AKA Pantothenate

*Pantoic acid + Beta-alanine = Pantothenic acid

*Pantothenic acid + Beta-mercaptoethylamine = Pantetheine

*Pantetheine + 3'-phospho-aDP = Coenzyme A (CoASH)

*CoASH + acetate = Acetyl CoA (Acetyl-SCoA)

*CoASH + LCFA = Long chain fatty acyl CoA

*CoA= active form of PA and an essential coenzyme in variety of rxns that sustain life

*In all plant and animal foods

*Good sources: liver, egg yolks, legumes

*In foods in various bound forms (CoA, CoA esters, acyl carrier protein, and glucose)

*Lost (~35-75%) in highly processed foods (refining, freezing and canning)

*Supplements= calcium pantothenate or as pantothenol

*In food- PA in free and bound forms

-85% in food is a component of CoA

*In lumen, CoA is hydrolyzed by phosphatases and pyrophosphatases to release PA

*Absorbed mostly in jejunum

*Passive diffusion at high concentrations

*Na+-dep active multivitamin transporter (SMVT) at low concentrations

*PA shares intestinal SMVT with biotin and lipoic acid

*40-60% of ingested PA is absorbed

*Panthenol (in multivitamins) is absorbed and converted to PA

*High doses of PA (10x vit) = ~10% reduction in PA absorption

*PA is found as free form in blood primarily bound to RBCs

*RBC [intracellular PA] > blood [extracellular PA]

*Cellular uptake

-Uptake of PA by tissues differs

-Heart, muscle, brain, kidney, liver uptake by Na⁺-Dep active transport (SMVT)

-Other tissues by facilitated diffusion

*In all mitochondria containing cells

*In cells, most PA is used to synthesize or resynthesize CoA (high in liver, adrenal gland, kidney, brain, heart)

*Small amounts are stored as PA and patetheine in RBCs and adipose tissue

*PA excreted intact mostly in urine

*Only small amounts via feces

*Urinary PA excretion reflects dietary intake

PA in CoA Synthesis

*PA becomes 4'-phosphopantotheine and CoA, which are the 2 functional forms

Functions:  

4'-phosphopantotheine

*FA synthesis

-Prosthetic group of Acyl Carrier Protein (ACP) domain of FA synthase

-In cytosol

-FA synthesis

-Fat/Carb/AA oxidation

-Ketone metabolism

*PA, as part of CoA, participates a lot in CHO, protein and fat metabolism, including degradation rxns resulting in energy production and synthetic rxns for the production of many vital compounds

-Cholesterol

-Bile salts

-Ketones bodies

-FAs

-Steroid hormones

-Neurotransmitter

CoA in oxidative decarboxylation in TCA

*PA joins thiamin, riboflavin, and niacin in oxidative decarboxylation of pyruvate to acetyl CoA

*Also in the oxidative decarboxylation of of alpha KG to succinyl CoA 

*4'-phosphopentetheine links directly to protein to form ACP

*ACP needed for FA synthesis

ACP in FA synthesis

*Affects activity, structure and localization of proteins

*Effects hormone fxn and activity: changes ability to bind to receptor

*Choline -->Acetylcholine

*Histone Acetylation: DNA transcription

Pathways Involving CoA

*Oral administration of PA and pantothenol ointment to the skin accelerate the closure of skin wounds and increase the strength of scar tissue

*Lowered total cholesterol

*Lowered TG

*May be helpful in combination with statins

*AI for Men and Women= 5mg/d

*This level is based on the amt needed to replace urinary excretion, assumed bioavailability of 50%

*[Blood PA]: <100mg/dL in blood = deficiency

*Urinary PA excretion = better indicator of status (<1mg/d = poor status)

*Rare

*Reported in conjunction with severe malnutrition

*Vomiting, fatigue, weakness, irritability

*Some conditions that increase need for PA: alcoholism, DM, and inflammatory bowel diseases

*Burning feet syndrome: numbness of toes, burning in feet. Corrected with calcium pantothenate administration

*No UL

*Low risk of toxicity

*Intakes of 100mg increase the excretion of niacin