crotonyl-coenzyme A [CoA] carboxylase, and propionyl-CoA carboxylase) whereas the fourth (acetyl-CoA carboxylase) is found in both the mitochondria and the cytosol. An inactive form of acetyl-CoA carboxylase has been postulated to serve as storage for biotin in the mitochondria (Allred and Roman-Lopez, 1988; Allred et al., 1989; Shriver et al., 1993).
Acetyl-CoA carboxylase catalyzes the carboxylation of acetyl CoA to form malonyl CoA. Malonyl CoA then serves as a substrate for fatty acid elongation. The second biotin-dependent carboxylase, pyruvate carboxylase, catalyzes the carboxylation of pyruvate to form oxaloacetate, which serves as an intermediate in the tricarboxylic acid cycle. Oxaloacetate thus formed is converted to glucose in the liver, kidney, and other gluconeogenic tissues.
A third biotin-dependent carboxylase, β-methylcrotonyl-CoA carboxylase, is required for the degradation of leucine, a branch-chained amino acid. Low activity of this enzyme resulting from biotin deficiency leads to the production of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine by an alternate pathway (Mock, 1996). Thus, elevated levels of these abnormal metabolites in urine reflect reduced activity of β-methylcrotonyl-CoA carboxylase, usually resulting from biotin deficiency.
A fourth biotin-dependent carboxylase, propionyl-CoA carboxylase, carboxylates propionyl-CoA to form D-methylmalonyl-CoA, which is racemized to the L-isomer, then undergoes isomerization to succinyl-CoA, and subsequently enters the tricarboxylic acid cycle. Reduction in activity of this carboxylase results in increased excretion of 3-hydroxypropionic acid and 3-methylcitric acid in urine (Mock, 1996).
In the normal breakdown of cellular proteins, these biotin-containing enzymes are degraded to biocytin (ε-N-biotinyl-L-lysine) or short oligopeptides containing biotin-linked lysyl residues (Mock, 1996). Biotinidase (earlier called biocytinase), a hydrolase, releases biotin from this oligopeptide for reuse (Mock, 1996).
Biotin exists as free biotin and in protein-bound forms in foods. The mechanism of intestinal hydrolysis of protein-bound biotin has not been well characterized, and little is known about factors that affect bioavailability. Although most dietary biotin appears to be protein bound in both meats and cereals, biotin in cereals appears to be less bioavailable (Mock, 1996). Avidin, a protein found in appreciable amounts in raw egg white, has been shown to bind