Vitamin B12 Cyanocobalamin

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Vitamin B-12 (Cyanocobalamin)

• Erin Kilelee
• UNCW
• Department of Chemistry and Biochemistry

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Function

• Involved in metabolism in every cell in the body
  (DNA synthesis, fatty acid synthesis, energy
  production)
• Important for function of
• Brain
• Nervous system
• Blood formation

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Symptoms of Deficiency

• Fatigue
• Depression
• Poor Memory
• Megaloblastic Anemia
• Gastrointestinal Symptoms
• Neurological Symptoms

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Discovery

• B-12 deficiency is the cause of pernicious anemia
  (fatal)
• George Whipple discovered that feeding dogs large
  amounts of liver cured the anemia
• The active ingredient (B-12) was isolated many
  years later

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Structure

• Most structurally complicated vitamin
• Corrin ring provides 4 coordination sites for
  central Co atom
• Dimethylbenzimidazole is the fifth
• R group provides the sixth and varies depending
  on the form

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The B-12 Family

• Vitamin B-12 is a name given to a class of
  chemically related compounds with vitamin
  activity

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Cyanocobalamin

• Cyanocobalamin is one member of the family
• Does not occur in nature
• Is converted to an active form in the liver (fist
  hydroxo then methyl and adenosyl)
• Most stable form of vitamin
• Cyanide added by charcoal columns used in
  purification

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Synthesis

• Not made by plants or animals
• Industrially synthesized by bacteria (Pseudomonas
  denitrificans)
• Robert Burns Woodward and Albert Eschenmoser were
  first to synthesize B-12

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Absorption and Distribution
From food Enters body bound to R-binders.
Stomach proteolysis requires an acidic pH, and
proteolytic enzyme- Supplements bypass this step
Gastric Parietal Cell Atropy- cause of
Pernicious Anemia TC-II/B-12 complex enters
cells by binding a receptor
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Methylmalonyl Coenzyme A Mutase (MUT)

• MUT uses AdoB-12 form
• Converts MMl-CoA to Su-CoA
• An important step in the extraction of energy
  from proteins and fats

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5-Methyltetrahydrofolate-homocysteine
methyltransferase (MTR)

• Also known as Methionine Synthase
• Methyl transfer enzyme uses MeB-12 to catalyze
  the conversion of amino acids Hcy into Met

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Without B-12

• These 2 reactions fail causing neurological
  damage
• The MUT reaction is required for myelin synthesis
  and other CNS functions
• Adenosine is required for methylation of myelin
  sheath phospholipids and the manufacture of
  neurotransmitters, catecholamines and in brain
  metabolism

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Metabolism and Excretion

• Metabolism occurs in the liver
• Half life of 6 days, but 400 days in the liver
• Renal Excretion

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Sources

• Meat (liver and shellfish)
• Milk Products
• Eggs contain B-12 but also a factor that blocks
  its absorption

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Supplements

• Tablets
• Liquid
• Strip
• Nasal Spray
• Injection
• Controversy over best method of delivery

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Side Effects

• Itching
• Rash
• Rosacea
• Diarrhea
• Vascular thrombosis
• Optic nerve atrophy

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Other Uses

• Hydroxocobalamin (IV) is used for treatment of
  cyanide poisoning
• Methylcobalamin by injection is being used to
  reduce oxidative stress in autism

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Drug Interactions

• Alcohol
• Aminosalicylic Acid
• Antibiotics
• Hormonal Contraception
• Chloromycetin
• Colchicine
• Colestid
• Zantac
• Nicotine
• Neomycin
• Nitrous Oxide
• Phenytoin
• AZT