Post on 11-Jan-2016
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.