Phar 722 Pharmacy Practice III

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Phar 722Pharmacy Practice III

• Vitamins-
• Biotin
• Spring 2006

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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

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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.

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Biotin Chemistry

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

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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.

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Addition of CO2 to biotin for subsequent
carboxylation reactions.
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Biotin Function-1

• Methylmalonyl CoA from propionyl CoA

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Biotin Function-2

• Oxalacetate from pyruvate (gluconeogenesis
  anapleurotic reactions)

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Biotin Function-3

• Formation of carbamyl phosphate (urea cycle)

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Biotin Function-4

• Malonyl CoA from acetyl CoA (fatty acid synthesis)

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Biotin Function-5

• Metabolism of leucine

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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.

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Hypervitaminosis Biotin

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

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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)

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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

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Sources

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