Phar 737 PathoBiopharmaceutical ChemistryScience

1
Phar 737Patho-Biopharmaceutical Chemistry/Science

• Vitamins-
• Pantothenic Acid
• Spring 2007

2
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

3
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.

4
Chemistry

• This vitamin can be considered a derivative of
  ß-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.

5
(No Transcript)
6
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.

7
(No Transcript)
8
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.

9
Hypervitaminosis

• There have been no reports of toxic doses.
• There is no UL.

10
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.

11
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.

12
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

13
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.

14
Phar 737Patho-Biopharmaceutical Chemistry/Science

• Vitamins-
• Biotin
• Spring 2007

15
Biotin Study Guide

• The applicable study guide items in the Vitamin
  Introduction
• History
• Structure of the vitamin and cofactor forms
• Function of the cofactor including specific types
  of reactions catalyzed
• Deficiency condition

16
History

• 1916
• It was recognized that rats fed a diet high in
  raw egg white exhibited muscle incoordination,
  dermatitis and loss of hair.
• Cooked egg white was not toxic.
• The toxicities from the raw egg white could be
  prevented by feeding liver or yeast to the
  animals.
• Deficiencies can be induced by a diet restricted
  to raw egg white.
• 1942
• The biotin structure was published.

17
Biotin Chemistry

• Biotin consists of two 5-membered rings cis-fused
  to each other.
• The d-isomer is the only active form.

18
Biotin Uptake and Metabolism

• Little is known about biotin uptake.
• There does not seem to be a cofactor form
  different from the basic structure.
• The carboxyl chain forms an amide linkage with
  the e-amino nitrogen of lysine which binds the
  vitamin to the enzyme's active site.
• Biotin is required for the addition of carbon
  dioxide in many, but not all, carboxylation
  reactions.
• There is some debate about the structure of the
  cofactor intermediate that transfers the carbon
  dioxide. See the next slide.

19
(No Transcript)
20
Addition of CO2 to biotin for subsequent
carboxylation reactions.
21
Biotin Function-1

• Methylmalonyl CoA from propionyl CoA

22
Biotin Function-2

• Oxalacetate from pyruvate (gluconeogenesis
  anapleurotic reactions)

23
Biotin Function-3

• Formation of carbamyl phosphate (urea cycle)

24
Biotin Function-4

• Malonyl CoA from acetyl CoA (fatty acid synthesis)

25
Biotin Function-5

• Metabolism of leucine

26
Biotin Deficiency

• One of the ways to induce a deficiency in humans
  is to feed the volunteer a raw egg white diet.
• Deficiency symptoms include hair loss, a rash
  around the nose and mouth, and conjunctivitis.
• A good source of biotin is egg yolk.
• Therefore, eating whole raw eggs will not cause a
  deficiency of this vitamin (although person could
  be at increased risk for salmonella poisoning).
• What is the problem with raw egg white?
• Egg white contains a basic protein known as
  avidin which forms salt linkages with the acidic
  biotin that might be in the intestinal tract
  (possibly produced by intestinal bacteria?).
• This complex is not absorbed, but remains in the
  intestine eventually to be excreted.
• Cooking the egg white ties up the avidin in the
  rest of the egg albumin preventing its binding
  biotin.

27
Hypervitaminosis Biotin

• None has been reported in humans.
• There is no UL.

28
Dosage Forms

• The synthetic racemic mixture is used
  commercially.
• As with racemic pantothenic acid and pantothenol,
  only half of the racemic biotin is active.
• Biotin is considered one of the more expensive
  vitamins and can add to the cost of the final
  product.
• Solubility 0.3 -0.4 mg/ml (1 gm/2,500-3,300 ml)

29
DRIs

• AI
• Infants 5 - 6 µg/day
• Children (1 - 13 years) 8 - 20 µg/day
• Adolescents (14 - 18 years) 25 µg/day
• Adults 30 µg/day
• Pregnancy 30 µg/day
• Lactation 35 µg/day
• EAR
• None reported
• RDA
• None reported
• UL
• None reported

30
Sources

• Liver
• Kidney
• Yeast
• Animal and plant tissue in general
• Possibly the intestinal bacteria