Question

The half life of GLP-1 in the plasma is less than 2 minutes, how is it metabolized?

Answer 1

Answer- Glucagon-like peptide-1 (GLP-1) is a 30 or 31 amino acid long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide.

Metabolism/degradation-

Once secreted, GLP-1 is extremely susceptible to the catalytic activity of the proteolytic enzyme dipeptidyl peptidase-4 (DPP-4). Specifically, DPP-4 cleaves the peptide bond between Ala8-Glu9 resulting in the abundant GLP-1 (9–36) amide constituting 60–80 % of total GLP-1 in circulation.

Neutral endopeptidase 24.11 (NEP 24.11) is a membrane-bound zinc metallopeptidase and is also identified accountable for the rapid degradation of GLP-1. It primarily cleaves peptides at the N-terminal side of aromatic amino acids or hydrophobic amino acids. However, its activity only becomes apparent once the degradation of DPP-4 has been prevented.