Biotin

Functions
Sources
Metabolism
Requirements
Deficiency
Toxicity

I.  Functions

1. Biotin is covalently bound to enzymes in cells
   1. Pyruvate carboxylase
      1. Catalyzes carboxylation of pyruvate to form oxaloacetate
      2. Requires acetyl CoA, ATP, and Mg⁺²
      3. If there is a surplus of ATP in the cell, the oxaloacetate is used for gluconeogenesis
      4. If there is a deficiency of ATP, the oxaloacetate will enter the Krebs cycle on condensation with acetyl CoA
   2. Acetyl CoA carboxylase
      1. Converts acetyl CoA to malonyl CoA
      2. This commits acetate units to fatty acid synthesis
      3. ATP and Mg⁺² are required
   3. Propionyl CoA carboxylase
      1. Catabolism of isoleucine, threonine, and methionine, which each generate propionyl CoA
      2. Catabolizes odd-number chain fatty acids which also generate propionyl CoA
      3. Catalyzes carboxylation of propionyl CoA to methylmalonyl CoA. The reaction requires ATP and Mg⁺²
      4. Methylmalonyl CoA is converted to succinyl CoA by racemase in a vitamin B12-dependent reaction
   4. B-methylcrotonyl CoA carboxylase
      1. B-methylcrotonyl CoA formed during leucine catabolism is carboxylated to form B-methylglutaconyl CoA
      2. this is further catabolized to generated acetoacetate and acetyl CoA

II.  Sources

1. Biotin is widely distributed in plants and animals
2. Yeast, liver, milk, cereals, tomatoes, and molasses are rich sources

III.  Metabolism

1. Absorption
   1. Protein bound biotin is catabolized by proteolytic enzymes to yield biocytin
   2. Biocytin is degraded by biotinidase to yield free biotin, lycine and other amino acids
   3. Biotin is absorbed primarily from the upper small intestine and in decreasing amounts further down
   4. Absorption is carrier mediated and thought to require Na. - Absorption may or may not require energy
   5. Both free and protein-bound biotin are found in plasma
   6. Uptake of biotin by tissues is related to need
   7. Distribution within cells corresponds to localization of carboxylases requiring biotin as the coenzyme
2. Excretion
   1. Biotin enzymes are catabolized by proteases to yield biocytin
   2. Biocytin is degraded by biotinidase to yield free biotin
      1. Some is reused
      2. Some is excreted
   3. Biotin and biocytin are excreted in urine
   4. Unabsorbed biotin is excreted in feces

IV.  Requirements

1. Human - RDA has not been established
   1. Uncertain contribution of intestinal synthesis
   2. Incomplete knowledge about bioavailability of food biotin
   3. Safe and adequate intake is estimated at 100-200 mg/day.
2. Poultry - 100-200 mg/kg BW
3. Rat - 300 mg/kg BW

V.  Deficiency

1. Human
   1. Factors increasing likelihood of deficiency
      1. Excess consumption of raw eggs
      2. Inflammatory bowel disease
      3. Achlorhydria (lack of HCI in gastric juice)
      4. Anticonvulsant drug therapy
      5. Alcoholism
   2. Deficiency symptoms
      1. Depression, hallucinations
      2. Muscle pain, paresthesia (burning, prickling sensation on the skin)
      3. Anorexia, nausea
      4. Alopecia, scaly dermatitis
2. Chicks
   1. Dermatitis in feet and beak, perosis
   2. Reduced hatchability
3. Pigs
   1. Alopecia, seborrheic skin lesions, cracks in feet
   2. Spasticity of hind legs

VI.  Toxicity

1. Toxicity of biotin has not been reported
2. Oral doses over 60 pg/day for over 6 months have not produced side effects

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