Biochemistry

Biotin is required for enzymatic activity of several important carboxylases (Table 28.10). Biotin is first attached to a lysine residue of biotin carboxyl carrier protein (BCCP) by biotin- [propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase (holocarboxylase [HCS], EC 6.3.4.10), which forms the biotinyl domain of the enzyme or separate subunit. The N1 position is subsequently carboxylated to form carboxy-biotin (Fig. 28.40), which is then able to transfer the carboxyl group to other substrates. The source of the carboxyl is either bicarbonate or decarboxylation of another substrate as is seen in transcarboxylation reactions.196 A typical carboxylation reaction mediated by biotin-BCCP is shown in Figure 28.41. The source of the carboxyl is bicarbonate with ATP supplying energy for the reaction. This is followed by the subsequent transfer of the carboxyl to the substrate with regeneration of the biotin-BCCP complex.

An interesting recent development is the finding that biotin is also attached to histones in the nucleus by the same enzyme involved in attachment to BCCP.197 The suggestion is that biotin may be involved in genetic regulation; although the exact role remains unknown at this time.

Deficiency states may rarely develop as a result of a biotin-deficient diet, as was observed in early, biotin-deficient TPN solutions,198 or as a result of prolonged feeding of large quantities of raw egg white.199 Raw egg white contains avidin, a protein that complexes biotin and interferes with its absorption from the gastrointestinal tract. A relative biotin deficiency has also been shown to occur in

TABLE 28.10 Biotin-Dependent Enzymes

Enzyme

EC Number

Function

Pyruvate

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