Biotin- Structure, sources, recommended daily allowance, absorption, storage and transportation, coenzyme role in carboxylation reactions, histone biotinylation, cell cycle regulation, beauty vitamin, egg white injury, and Leiner's disease

1. Biotin- Chemistry, functions
and clinical significance
Namrata Chhabra
MHPE, MD, CMCL FAIMER FELLOW- REGIONAL INSTITUTION,
Principal-in-charge, Professor& Head, Department of Biochemistry,
SSR Medical College, Mauritius

2. Introduction
• A Sulphur-containing water-soluble vitamin,
• Also known as: Bios, vitamin H, Co-enzyme R,
Anti egg-white injury factor.
• Chemically, a heterocyclic monocarboxylic
acid.
• Consists of two fused rings, one imidazole and
the other thiophene.
• C10 H16 O3 N2S
• Hexahydro-2-oxo-1-thieno-3,4-imidazole-4
valeric acid.
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3. Chemical forms of Biotin
• Two forms with essentially identical biological activities:
• α-Biotin (egg-yolk) and β-Biotin (Liver)-differing only in the nature of the
side chain.
• Biotin is said to occur both as free form and bound form in tissues and
foods.
• Bound forms: Biocytin, desthiobiotin and oxybiotin are the bound forms.
• Biocytin (ε-N-biotinyl-Lysine): remains bound with ‘Lysine’ residues of
tissue proteins by amide bonds. It is released on hydrolyzing the peptide
bonds between the biotin-bound Lysine and the peptide chain.
• Desthiobiotin and oxybiotin: These are biologically active in certain strains
of yeast and bacteria.
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4. Biosynthesis and Metabolism
• Biotin can be synthesized by many bacteria, yeast, and fungi.
• In green plants, it may be formed in leaf and root.
• Coenzyme-R is a growth essential for the nitrogen fixing organisms,
Rhizobium, in the root nodules of Leguminous plants.
• Coenzyme R has been proved to be Biotin.
• Human beings cannot synthesize the vitamin
• It must be supplied in diet.
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5. Storage and excretion
• Biotin may be stored to a limited extent in the liver and kidneys.
• Excretion: Excreted in urine, feces and milk.
• Normal adult on an adequate diet excretes 10 to 180 μg in urine and
15 to 200 μg daily in the feces.
• Fecal excretion represents unabsorbed biotin synthesized by intestinal
bacteria.
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6. Sources of Biotin
• Animal sources: liver, kidney, milk and milk products and egg-yolk.
• Vegetable sources: vegetables, legumes, and grains
• Large amounts are present in royal jelly (bee).
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7. Recommended daily allowance
• Adults : 25 to 50 μg daily
• Infants : 10 to 15 μg daily
• Children : 20 to 40 μg daily
• Requirement Increases in
• Pregnancy and lactation,
• Oral antibiotic therapy for prolonged periods
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8. Functions of Biotin
1) Role in carboxylation reactions
• Biotin functions to transfer carbon
dioxide in a few carboxylation
reactions such as :
• Acetyl-CoA,
• Pyruvate,
• Propionyl-CoA, and
• Methyl crotonyl-CoA carboxylases).
• Biotin is attached at the active site
of carboxylases.
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9. General reaction catalyzed by Biotin
• The reactive intermediate is
1 N carboxy biocytin, formed
from bicarbonate in an ATP-
dependent reaction. The
carboxy group is then
transferred to the substrate
for carboxylation.
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10. Acetyl-CoA carboxylase
• Acetyl-CoA carboxylase catalyzes
the binding of bicarbonate to
acetyl-CoA to form malonyl-CoA.
• Malonyl-CoA is required for the
synthesis of fatty acids and
functions in regulating
mitochondrial fatty acid
oxidation.
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11. Pyruvate carboxylase
• Pyruvate carboxylase is a critical
enzyme in gluconeogenesis—the
formation of glucose from sources
other than carbohydrates, for
example, amino acids.
• Oxaloacetate formed from pyruvate
can be utilized in many other ways
depending upon the need of the
cell
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12. Propionyl-CoA carboxylase
• Propionyl-CoA carboxylase
catalyzes essential steps in the
metabolism of certain amino
acids, cholesterol, and odd chain
fatty acids.
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13. Anaplerotic reactions
• Anaplerotic reactions catalyzed
by biotin dependent pyruvate
carboxylase (PC) and Propionyl-
coenzyme A carboxylase (PCC)
regenerate oxaloacetate for the
citric acid cycle
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14. Methyl crotonyl-CoA carboxylase
• catalyzes an
essential step in
the catabolism of
leucine, an
essential amino
acid.
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15. 2) Role of Biotin in cell cycle regulation
• Biotin also has a role in regulation
of the cell cycle, acting to
biotinylate key nuclear proteins
such as histones and other
proteins.
• Biotinylation of histones plays a
role in regulating DNA replication
and transcription as well as
cellular proliferation and other
cellular responses
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16. “Beauty vitamin”
• It also activates protein/amino acid metabolism in the hair roots and
fingernail cells.
• Due to its beneficial effects for hair, skin and nails, biotin is also
known as the “beauty vitamin”.
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17. Egg white injury
• Raw egg whites contain Avidin, a glycoprotein that strongly binds with
biotin and prevents its absorption.
• Once a biotin-avidin complex forms, the bond is essentially irreversible; the
biotin-avidin complex is not broken during passage of the food bolus
through the stomach and intestines.
• As a result, biotin is not liberated from food, and the biotin-avidin complex
is lost in the feces.
• Thus, the ingestion of large quantities of raw egg white over a long period
can result in a biotin deficiency.
• Cooking egg white denatures avidin, rendering it susceptible to digestion
and therefore unable to prevent the absorption of dietary biotin.
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18. Deficiency manifestations
• Dermatitis of the extremities,
• Pallor of skin and mucous membranes,
• Anorexia and nausea,
• muscle pains
• Hyperesthesia, Depression, Lassitude and Somnolence,
• Anemia, and hypercholesterolemia.
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19. Deficiency disease
• No deficiency disease has been reported.
• Two conditions have been reported:
1. Congenital holocarboxylase synthase deficiency:
The enzyme helps to utilize biotin in metabolic role.
The affected children fail to utilize biotin and develop biotin deficiency
which is manifested as dermatitis, graying of hair, loss of hair (alopecia)
and incoordination of movements.
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20. Deficiency disease
• Acquired (Leiner’s disease): Leiner’s disease (erythroderma
• desquamativum or exfoliative dermatitis) in young infants has been
reported by several workers.
• The disease often occurs in breastfed infants, frequently in association
• with persistent diarrhea.
• The low biotin content of human milk together with the poor absorption of
biotin due to diarrhea, appears to cause biotin deficiency.
• Administration of biotin has been reported to cause a cure in many of
these cases
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21. Summary
• A Sulphur-containing water-soluble vitamin.
• Biotin functions to transfer carbon dioxide in a few carboxylation
reactions such as : Acetyl-CoA, Pyruvate, Propionyl-CoA, and Methyl
crotonyl-CoA carboxylases.
• Biotin also has a role in regulation of the cell cycle, acting to
biotinylate key nuclear proteins such as histones and other proteins.
• It also activates protein/amino acid metabolism in the hair roots and
fingernail cells. Due to its beneficial effects for hair, skin and nails,
biotin is also known as the “beauty vitamin”.
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