Amino-terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV).
Increased concentrations of procalcitonin (PCT) are found in the plasma of patients with thermal injury and in patients with sepsis and severe infection, making this molecule important as a diagnostic and prognostic marker in these diseases. Interestingly, only the truncated form of PCT, PCT(3-116), is present in the plasma of these patients. The enzyme responsible for this truncation is unknown as yet. Here, using capillary zone electrophoresis, mass spectrometry and Edman sequence analysis, we demonstrate that dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) is capable of catalyzing the hydrolysis of PCT(1-116), releasing the N-terminal dipeptide Ala-Pro. We hypothesize that PCT(3-116) is the result of the hydrolysis of PCT(1-116) by soluble DP IV of the blood plasma or by DP IV expressed on the surface of cells.
Wrenger
S
S
Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120, Magdeburg, Germany.
Kähne
T
T
Bohuon
C
C
Weglöhner
W
W
Ansorge
S
S
Reinhold
D
D
D001424:Bacterial Infections / Q000097:blood* / Q000201:enzymology; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000235:genetics; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012995:Solubility; D013379:Substrate Specificity
D015415:Biomarkers; C000606589:CALCA protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D010446:Peptide Fragments; D011480:Protease Inhibitors; D011498:Protein Precursors; D002116:Calcitonin; D018819:Dipeptidyl Peptidase 4; D015740:Calcitonin Gene-Related Peptide