peptide amidation

Definition

Target type: biologicalprocess

The posttranslational conversion of C-terminal glycine-extended peptides to C-terminal alpha-amidated peptides. Occurs to over half of all peptide hormones to give bioactive peptides. This is a two step process catalyzed by a peptidyl-glycine alpha-hydroxylating monooxygenase and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase. In some organisms, this process is catalyzed by two separate enzymes, whereas in higher organisms, one polypeptide catalyzes both reactions. [PMID:11028916]

Peptide amidation is a post-translational modification that converts the C-terminal carboxyl group of a peptide to an amide group. This process is catalyzed by a family of enzymes called peptidyl-glycine alpha-amidating monooxygenase (PAM). PAM enzymes are found in all eukaryotes and some prokaryotes, and they play a crucial role in the biosynthesis of a wide variety of bioactive peptides, including hormones, neurotransmitters, and neuropeptides.

The amidation reaction occurs in two steps. In the first step, the C-terminal glycine residue of the peptide is hydroxylated to form a glycyl hydroxamic acid intermediate. This reaction is catalyzed by the copper-containing enzyme peptidyl-glycine alpha-hydroxylating monooxygenase (PHM). In the second step, the glycyl hydroxamic acid intermediate is dehydrogenated to form the amide product. This reaction is catalyzed by the enzyme peptidyl-alpha-amidating monooxygenase (PAM).

The amidation process is highly regulated and is influenced by a variety of factors, including the availability of substrates, the activity of PAM enzymes, and the presence of regulatory proteins. The regulation of peptide amidation is important for controlling the activity and bioavailability of bioactive peptides.

Amidation is a crucial process in the biology of many organisms. It is involved in a variety of physiological processes, including:

* **Hormone signaling:** Amidation is required for the biosynthesis of many hormones, including glucagon, adrenocorticotropic hormone (ACTH), and vasoactive intestinal peptide (VIP).
* **Neurotransmission:** Amidation is required for the biosynthesis of many neurotransmitters, including neuropeptide Y (NPY) and substance P.
* **Immune function:** Amidation is required for the biosynthesis of several immune system peptides, including chemokines and cytokines.
* **Development:** Amidation is required for the biosynthesis of several developmental peptides, including growth factors and morphogens.

Defects in peptide amidation can lead to a variety of diseases, including:

* **Diabetes:** Deficiency in glucagon amidation can lead to diabetes.
* **Neurological disorders:** Deficiency in neuropeptide amidation can lead to neurological disorders, such as epilepsy and Parkinson's disease.
* **Immune deficiencies:** Deficiency in immune system peptide amidation can lead to immune deficiencies.
* **Developmental disorders:** Deficiency in developmental peptide amidation can lead to developmental disorders, such as dwarfism and mental retardation.

In conclusion, peptide amidation is an essential post-translational modification that plays a crucial role in the biosynthesis of a wide variety of bioactive peptides. The amidation process is highly regulated and is influenced by a variety of factors. Defects in peptide amidation can lead to a variety of diseases.'
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Proteins (1)

Compounds (3)