Peptidylglycine hydroxylase

A number of peptide hormones have a carboxyl terminal amide which is derived from a glycine terminal residue. This glycine is hydroxylated on the a-carbon by a copper-containing enzyme, peptidylglycine hydroxylase, which, again, requires ascorbate for reduction of Cu ". ... 

Peptidylglycine monooxygenase [EC 1.14.17.3], also known as peptidyl a-amidating enzyme and peptidylglycine 2-hydroxylase, catalyzes the reaction of a peptidylglycine with ascorbate and dioxygen to produce a pepti-dyl(2-hydroxyglycine), dehydroascorbate, and water. 

PEPTIDYL GLYCINE a-AMIDATING MONOOXYGENASE Peptidylglycine 2-hydroxylase,... 

Tyrosinase is both an oxidase and a hydroxylase. Some other copper enzymes have only a hydroxylase function. One of the best understood of these is the peptidylglycine a-hydroxylating monoxygenase, which catalyzes the first step of the reaction of Eq. 10-11. The enzyme is a colorless two-copper protein but the copper atoms are 1.1 nm apart and do not form a binuclear center.570 Ascorbate is an essential cosubstrate, with two molecules being oxidized to the semidehydro-ascorbate radical as both coppers are reduced to Cu(I). A ternary complex of reduced enzyme, peptide, and 02 is formed and reacts to give the hydroxylated product.570 A related two-copper enzyme is dopamine (J-monooxygenase, which utilizes 02 and ascorbate to hydroxylate dopamine to noradrenaline (Chapter 25).571/572 These and other types of hydroxylases are compared in Chapter 18. 

Oxygenation tyrosinase, dopamine /3-hydroxylase, phenylalanine hydroxylase, peptidylglycine a-amidating monooxygenase... 

A similar copper-dependent hydroxylase constitutes the N-terminal domain of the peptidylglycine a-amidating enzyme (Eq. 10-11). This bifunctional enzyme hydroxylates C-terminal glycines in a group of neuropeptide hormones and other secreted peptides. The second functional domain of the enzyme cleaves the hydroxylated glycine to form a C-terminal... 

Also extensively studied are dicopper monooxygenases involved in the regulation of neurotransmitters. Dopamine p-hydroxylase (DpH) catalyzes the stereospecific benzylic hydroxylation of dopamine for the biosynthesis of the hormone norepinephrine, while peptidylglycine a-hydroxylating... 

Fig. 3. Reactivity and proposed mechanism of dopamine P-hydroxylase and peptidylglycine a-hydroxylating monooxygenase.

Dopamine p-hydroxylase Phenylalanine hydroxylase Peptidylglycine a-amidating monooxygenase Particulate MMO... 

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