Enzymatic activity of D-BP fails if the<unk>  cannot effectively bind the cofactor NAD+, as shown in the G16S mutation. Glycine 16 forms a short loop and creates a hole for the adenine ring of NAD+ to enter. Other amino acid side chains alter the shape of this loop due to steric hindrance, and prevent proper NAD+ binding. Other mutations that exist are due to incorrect polypeptide folding. L405 (leucine located at residue 405) located in the substrate binding domain of the hydratase 2 unit, plays an important role in binding CoA ester moiety. One mutation seen in D-BP deficiency patients is caused by a leucine to proline substitution. This breaks the hydrophobic interactions necessary for proper substrate binding with CoA esters.
D-bifunctional protein deficiency
Glutaminase deficiency
Biotinidase deficiency
Aminoacylase 1 deficiency
Holocarboxylase synthetase deficiency
Ornithine aminotransferase deficiency
Arginine:glycine amidinotransferase deficiency
Multiple carboxylase deficiency