Despite the similarity in how proteins bind the two coenzymes, enzymes almost always show a high level of specificity for either NAD or NADP. This specificity reflects the distinct metabolic roles of the respective coenzymes, and is the result of distinct sets of amino acid residues in the two types of coenzyme-binding pocket. For instance, in the active site of NADP-dependent enzymes, an ionic bond is formed between a basic amino acid side-chain and the acidic phosphate group of NADP. On the converse, in NAD-dependent enzymes the charge in this pocket is reversed, preventing NADP from binding. However, there are a few exceptions to this general rule, and enzymes such as aldose reductase, glucose-6-phosphate dehydrogenase, and methylenetetrahydrofolate reductase can use both coenzymes in some species.