Novel insights into peptide amidation and amidating activity in the human circulation
C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction.
\nPeptide amidation is a critical post-translational modification for several hormone peptides, with peptidylglycine α-amidating monooxygenase (PAM) being the sole catalyst. The presence of PAM amidating activity (AMA) in human circulation has been reported, yet its clinical significance and physiological role remain unclear.\n\nA novel assay was developed to quantify serum amidating activities using Adrenomedullin-Gly as a substrate. Serum amidating activities were measured in a large cohort of 4900 individuals, revealing correlations with various clinical parameters including high blood pressure. Notably, increased PAM-AMA levels were associated with adverse outcomes related to hemodynamic stress, such as cardiovascular mortality and atrial fibrillation over an 8.8 ± 2.5 year follow-up period.\n\nFurther insights into the physiological role of circulating PAM were gained from an animal study using recombinant human PAM. These results suggest that circulating PAM may play a significant role in peptide amidation and have implications for understanding its clinical significance.\n\nThis study highlights the importance of elucidating the mechanisms behind PAM amidating activity, which could contribute to the development of novel biomarkers for cardiovascular disease and other conditions.\n\nLimitations of this study include the need for further research into the specific substrates involved in PAM amidation and the potential applications of these findings.\n\nIn conclusion, the discovery of PAM amidating activity in human circulation underscores the complex interplay between peptide modification and physiological processes.