Glutaminyl cyclase activity is a characteristic feature of human cerebrospinal fluid.
BACKGROUND
Proteins and peptides occurring in human body fluids can be useful biological markers for neurological diseases and can even contribute to the pathogenesis of such diseases. However, proteins and peptides are potential substrates of proteases and other enzymes. Proteolysis and enzymatic modification may lead to their degradation and modification.


METHODS
Using mass spectrometry we investigated the degradation and modification of indicator peptides in the presence of cerebrospinal fluid (CSF). We further applied a fluorometric assay to study the activity of the presumed enzyme glutaminyl cyclase.


RESULTS
In CSF we observed an aminopeptidase activity that could partially be inhibited by protease inhibitors and EDTA. In addition, the formation of pyroglutamate (pGlu) from N-terminal glutamine (Gln) was regularly observed. The reaction to pGlu was rapid and protected the indicator peptides from further N-terminal degradation. The conversion of Gln to pGlu could be attributed to the activity of the enzyme glutaminyl cyclase (QC). The QC activity was a characteristic feature of all 45 CSF samples collected from multiple sclerosis patients and controls.


CONCLUSIONS
Glutaminyl cyclase activity is a characteristic feature of human cerebrospinal fluid. The presence of QC in CSF can stabilize peptides from degradation by aminopeptidases. This may have impact for neurological disorders that are characterized by both, the presence of QC and the occurrence of appropriate peptide substrates.
Gontsarova
Anastassia
A
Institute of Pathophysiology, University of Greifswald, Karlsburg, Germany.
Kaufmann
Eckhard
E
Tumani
Hayrettin
H
Dressel
Alexander
A
Mandel
Friedrich
F
Wiesmüller
Karl-Heinz
KH
Kunert-Keil
Christiane
C
Brinkmeier
Heinrich
H
D019881:Aminoacyltransferases / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid
D015415:Biomarkers; D019881:Aminoacyltransferases; C059280:glutaminyl-peptide cyclotransferase