Peptidyl glycine α-amidation activity has been detected in human plasma and in several human tissues known to synthesize biologically active α-amidated peptides. Activity was monitored by measuring conversion of mono-[125I]-D-Tyr-Val-Gly into mono-[125I]-D-Tyr-Val-NH2. The plasma α-amidation activity is dependent on molecular oxygen, copper, and ascorbic acid and appears to recognize a variety of peptide substrates which contain carboxyl terminal glycine residues. Kinetic analyses demonstrated Michaelis-Menten kinetics with a Km of 14 μmol/L for D-Tyr-Val-Gly. Based on gel filtration, the apparent molecular weight of the peptidyl glycine α-amidation activity in human serum is 60,000. The level of peptidyl glycine α-amidation activity in adult plasma (N = 17) was 106 ± 3 pmol/mL/h (Mean ± SEM) with no difference between male and female subjects (range 84 to 126 pmol/mL/h). In subjects under 15 years old (N = 10), mean plasma activity was 128 ± 10 pmol/mL/h, higher than values for adult control plasma (P < .05). In serum from hypothyroid adults (N = 13), mean serum activity was 141 ± 11 pmol/mL/hr, higher than euthyroid controls (P < .025). The most striking elevations in α-amidation activity occurred in plasma from patients with peptide-secreting tumors. Patients with medullary thyroid carcinoma (N = 19) had a mean plasma peptidyl glycine α-amidation activity of 142 ± 52 pmol/mL/h (range 84 to 435 pmol/mL/h). The level of plasma α-amidation activity in one patient with metastatic carcinoid tumor was 560 pmol/mL/h. Peptidyl glycine α-amidation activity was detected in extracts of pituitary and central nervous system tissue, but was not detected in significant amount in extracts of various peripheral tissues. Extracts of peptide-secreting tumors also contained peptidyl glycine α-amidation activity. Human peptidyl glycine α-amidation activity may be co-secreted from tissue along with amidated peptide hormones and serve as a useful marker for certain endocrine tumors.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism