Vitamin C in copper- and iron-containing hydroxylases
THE CONTEXT
Ascorbate supports specific hydroxylase reactions and also acts as a reducing agent and oxygen radical quencher.
Copper-containing hydroxylases
•
Dopamine β-hydroxylase is a copper-containing enzyme involved in catecholamine synthesis from tyrosine in the adrenal medulla and central nervous system.
•
During hydroxylation, Cu+ is oxidized to Cu2+. Ascorbate specifically reduces it back to Cu+ and is oxidized to monodehydroascorbate.
•
Some peptide hormones acquire a carboxy-terminal amide from terminal glycine. Peptidylglycine hydroxylase hydroxylates this glycine at its α-carbon and requires ascorbate for copper reduction.
Iron-containing hydroxylases
•
These ascorbate-requiring enzymes link substrate hydroxylation to oxidative decarboxylation of α-ketoglutarate; many modify precursor proteins.
•
Proline and lysine hydroxylases are required for postsynthetic conversion of procollagen to collagen. Proline hydroxylase also contributes to formation of osteocalcin and the C1q component of complement.
•
Aspartate β-hydroxylase modifies the precursor of protein C, a vitamin K-dependent protease that hydrolyzes activated factor V.
•
Trimethyllysine and γ-butyrobetaine hydroxylases participate in carnitine synthesis.
Role of ascorbate
•
In the iron-containing enzymes, ascorbate reduces the iron prosthetic group after accidental oxidation during the reaction. It is neither consumed stoichiometrically with substrates nor assigned a simple catalytic role.
•
Ascorbate can also increase other enzyme activities in vitro through nonspecific reducing action and has nonenzymic effects as a reducing agent and oxygen radical quencher.