Avidin an egg protein has great affinity to a vitamin. Discuss the biochemical role of that vitamin.

Biotin: Structure and Properties

Biotin is a water-soluble vitamin belonging to the B-complex group. Its structure consists of a ureido ring fused with a tetrahydrothiophene ring, carrying a valeric acid side chain. This structure is critical for its function as a coenzyme. Biotin is relatively stable to heat but can be destroyed by prolonged exposure to alkaline conditions.

Biochemical Role of Biotin

Biotin functions as a coenzyme for four crucial carboxylase enzymes. These enzymes catalyze the addition of carbon dioxide (CO2) to various substrates, a process known as carboxylation. These reactions are vital for several metabolic pathways:

• Pyruvate Carboxylase: Converts pyruvate to oxaloacetate, a key step in gluconeogenesis (the synthesis of glucose from non-carbohydrate sources) and the citric acid cycle.
• Acetyl-CoA Carboxylase: Catalyzes the formation of malonyl-CoA from acetyl-CoA, the rate-limiting step in fatty acid synthesis. There are two isoforms: ACC1 (involved in fatty acid synthesis) and ACC2 (involved in fatty acid oxidation regulation).
• Propionyl-CoA Carboxylase: Converts propionyl-CoA to methylmalonyl-CoA, an essential step in the metabolism of odd-chain fatty acids and certain amino acids (isoleucine, valine, methionine, and threonine).
• β-Methylcrotonyl-CoA Carboxylase: Catalyzes the formation of β-methylglutaconyl-CoA from β-methylcrotonyl-CoA, involved in leucine catabolism.

Mechanism of Biotin-Dependent Carboxylation

The carboxylase enzymes utilize biotin covalently linked to a lysine residue within the enzyme's active site. The carboxylation process involves several steps:

1. Biotin is carboxylated by bicarbonate (HCO3-) to form carboxybiotin, utilizing ATP.
2. Carboxybiotin then transfers the CO2 group to the substrate, catalyzed by the carboxylase enzyme.
3. Biotin is regenerated, ready for another round of carboxylation.

Clinical Significance of Biotin Deficiency

Biotin deficiency is relatively rare, as it is widely available in foods and can also be synthesized by gut bacteria. However, deficiency can occur in specific situations:

• Genetic Defects: Mutations in the genes encoding biotinidase (an enzyme that cleaves biotin from dietary proteins) or holocarboxylase synthetase (an enzyme that attaches biotin to carboxylase enzymes) can lead to biotinidase deficiency or holocarboxylase synthetase deficiency, respectively.
• Excessive Consumption of Raw Egg Whites: Avidin binds tightly to biotin, preventing its absorption in the intestine. Consuming large quantities of raw egg whites over a prolonged period can induce biotin deficiency.
• Total Parenteral Nutrition (TPN): Individuals receiving long-term TPN without adequate biotin supplementation may develop deficiency.

Symptoms of biotin deficiency include:

• Dermatitis (often around the eyes, nose, and mouth)
• Alopecia (hair loss)
• Neurological symptoms (lethargy, depression, ataxia)
• Metabolic acidosis

Biotin and Disease

Beyond deficiency, biotin supplementation is sometimes used in conditions like multiple sclerosis, although evidence for its efficacy remains limited and controversial. Biotin is also used in diagnostic testing for biotinidase deficiency through a newborn screening program.

Enzyme	Reaction Catalyzed	Metabolic Pathway
Pyruvate Carboxylase	Pyruvate + CO2 → Oxaloacetate	Gluconeogenesis, Citric Acid Cycle
Acetyl-CoA Carboxylase	Acetyl-CoA + CO2 → Malonyl-CoA	Fatty Acid Synthesis
Propionyl-CoA Carboxylase	Propionyl-CoA + CO2 → Methylmalonyl-CoA	Odd-Chain Fatty Acid Metabolism, Amino Acid Metabolism
β-Methylcrotonyl-CoA Carboxylase	β-Methylcrotonyl-CoA + CO2 → β-Methylglutaconyl-CoA	Leucine Catabolism