Phar 722Pharmacy Practice III

Vitamins-Pantothenic Acid

Spring 2006

Pantothenic Acid Study Guide• The applicable study guide items in the

Vitamin Introduction• History• Structure• The advantages of Pantothenyl Alcohol

over Calcium Pantothenate• Function of the vitamin• Function of Coenzyme A• Deficiency condition• Commercial forms of the vitamins

History• Pantothenic Acid was isolated in the

1930s at the University of Oregon and Oregon State College from yeast and liver.

• At various times it was known as Vitamin B3 and B5.

Chemistry• This vitamin can be considered a

derivative of β-alanine.

• It is asymmetric. – The natural form is D(+). – Only the D(+) isomer is active.

• The reduced alcohol form, pantothenol, is considered as equally active as the parent acid.

HO C

O

CH2 CH2 NH C

O

CH

OH

C

CH3

CH3

CH2OH

Pantothenic Acid

-O C

O

CH2 CH2 NH C

O

CH

OH

C

CH3

CH3

CH2OH

Sodium Pantothenate

-O C

O

CH2 CH2 NH C

O

CH

OH

C

CH3

CH3

CH2OH

Calcium Pantothenate;commercial form;Solubility: 1 gm/2.8 ml;Unstable to autoclaving

Ca++

2

HO CH2 CH2 CH2 NH C

O

CH

OH

C

CH3

CH3

CH2OH

Pantothenol;commercial form;freely soluble; stable

Na+

-alanine

Uptake and Metabolism• Little is known about the specifics of

pantothenic acid and pantothenol uptake. • The conversion of the provitamin

pantothenol readily occurs. • Pantothenic acid is a structural component,

but not the active site, of coenzyme A. – This is different from other B vitamins who have

direct coenzyme/cofactor roles.

• The biosynthesis of coenzyme A occurs presumably in the tissues requiring it. – Because coenzyme A is required for nearly all

acyl transfers, synthesis would take place in nearly all cells.

-O2C

CH2

CH2

HN

C

CH CH2

OH

O

OH

H3C CH3

Pantothenic Acid

-O2C

CH2

CH2

HN

C

CH CH2

O

O

OH

H3C CH3

4'-Phosphopantothenate

ATP ADP

Pantothenatekinase

C

CH2

CH2

HN

C

CH CH2

O

O

OH

H3C CH3

4'-Phosphopantothenoylcysteine

Phosphopantothenoylcysteinesynthetase

ATP +

ADP + Pi

HN

O

CH

CH2

HS

CO2-

C

CH2

CH2

HN

C

CH CH2

O

O

OH

H3C CH3

4'-Phosphopantetheine

HN

O

CH2

CH2

HS

CO2

Phosphopantothenoylcysteinedecarboxylase

N

NN

N

NH2

O

OHOPO3-2

HH

HH

OP

O-

O

C

CH2

CH2

HN

C

CH CH2

O

OH

H3C CH3

HN

O

CH2

CH2

HS

O P O

O

O-

Coenzyme A (CoASH)

2 ATP

ADP + PPi

1. Dephospho-CoA pyrophosphorylase

2. Dephospho-CoA kinase

PO3-2

Cys

PO3-2

PO3-2

2 PiAcyl groups formhigh energy thiolesters (Acetyl CoA)

Pantothenic Acid Deficiency

• Pantothenic acid is essential in humans.

• No specific deficiency symptoms have been described. – Pantothenic acid deficiencies reported in WW

II prisoners of war.– The symptoms were of neurological nature.

Hypervitaminosis • There have been no reports of toxic

doses.

• There is no UL.

Dosage Forms-1• Nearly all forms use a synthetic,

racemic mixture. – This means that double the amount of

synthetic vitamin must be used to obtain equivalent active vitamin.

– This approach is cheaper than separating the synthetic product into each of the isomers.

• For stability reasons, pantothenic acid is rarely used in vitamin supplements.

Dosage Forms-2• Calcium Pantothenate

– Commonly used in dry dosage forms.– Moderately hygroscopic– Solubility 1 gm/2.8 ml– Unstable for autoclaving

• Pantothenol (Panthenol)– Reasonably stable– Freely soluble– Used in injectable dosage forms.– Also found in oral dosage forms.

• Topical Pantothenol Preparations– There is no evidence that this vitamin is effective as a vitamin

topically. • It apparently has good emollient properties, but these have nothing to

do with its systemic role.• It is used in shampoos because it leaves the hair “slippery” for

combing. The comb slides easily through the hair.

DRIs• AI

– Infants 1.7 - 1.8 mg/day– Children (1 - 13 years) 2 - 4 mg/day– Everyone else 5 mg/day– Pregnancy 6 mg/day– Lactation 7 mg/day

• EAR– None reported

• RDA– None reported

• UL– None reported

Food Sources

• All animal and plant tissues

• It is assumed we obtain the vitamin from coenzyme A found in the food we eat.

• Based on cell culture experiments, our intestinal flora may release pantothenic acid.– The fact that prisoners of war have experienced

deficiencies of this vitamin indicate that intestinal flora may not be a significant source.