Peptidyl-glycine alpha-amidating monooxygenase is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that catalyzes the conversion of glycine amides to amides and glyoxylate. The enzyme is involved in the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

of many signaling peptides and some fatty acid amides. In humans, the enzyme is encoded by the '' PAM''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. This transformation is achieved by conversion of a prohormone to the corresponding amide (C(O)NH₂). This enzyme is the only known pathway for generating peptide amides, which renders the peptide more hydrophilic.

Function

This gene encodes a multifunctional protein. It has two enzymatically active domains with catalytic activities - peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). These

catalytic domain In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

s work sequentially to catalyze

neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they b ...

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s to active alpha-amidated products. The reaction pathway catalyzed by PAM is accessed via quantum tunneling and substrate preorganization. Multiple alternatively spliced transcript variants encoding different

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

s have been described for this gene, but some of their full-length sequences are not yet known. The PHM subunit effects hydroxylation of an O-terminal glycine residue: :peptide-C(O)NHCH₂CO₂⁻ + O₂ + 2 → peptide-C(O)NHCH(OH)CO₂⁻ + H₂O Involving hydroxylation of a hydrocarbon by O₂, this process relies on a

copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...

cofactor.

Dopamine beta-hydroxylase Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine. The three substrates of ...

, also a copper-containing enzyme, effects a similar transformation. The PAL subunit then completes the conversion, by catalyzing elimination from the hydroxylated glycine: :peptide-C(O)NHCH(OH)CO₂⁻ → peptide-C(O)NH₂ + CH(O)CO₂⁻ The eliminated coproduct is

glyoxylate Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially. Str ...

, written above as CH(O)CO₂⁻.

In insects

Insect PαAMs are responsive to O concentrations and depends upon Cu. Simpson et al 2015 finds insect PαAMs to respond to

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

by regulating the activity of several

peptide hormone Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...

s. They find PαAM to probably be an important part of

responses to hypoxia.

Function

In insects

References

Further reading