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Amino Acids

, Volume 38, Issue 5, pp 1607–1615 | Cite as

Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity

  • Verena PetersEmail author
  • Moustafa Kebbewar
  • Erwin W. Jansen
  • Cornelis Jakobs
  • Eva Riedl
  • Hannes Koeppel
  • Dirk Frey
  • Katja Adelmann
  • Kristina Klingbeil
  • Matthias Mack
  • Georg F. Hoffmann
  • Bart Janssen
  • Johannes Zschocke
  • Benito A. Yard
Original Article

Abstract

Activity of carnosinase (CN1), the only dipeptidase with substrate specificity for carnosine or homocarnosine, varies greatly between individuals but increases clearly and significantly with age. Surprisingly, the lower CN1 activity in children is not reflected by differences in CN1 protein concentrations. CN1 is present in different allosteric conformations in children and adults since all sera obtained from children but not from adults were positive in ELISA and addition of DTT to the latter sera increased OD450 values. There was no quantitative difference in the amount of monomeric CN1 between children and adults. Further, CN1 activity was dose dependently inhibited by homocarnosine. Addition of 80 μM homocarnosine lowered V max for carnosine from 440 to 356 pmol/min/μg and increased K m from 175 to 210 μM. The estimated K i for homocarnosine was higher (240 μM). Homocarnosine inhibits carnosine degradation and high homocarnosine concentrations in cerebrospinal fluid (CSF) may explain the lower carnosine degradation in CSF compared to serum. Because CN1 is implicated in the susceptibility for diabetic nephropathy (DN), our findings may have clinical implications for the treatment of diabetic patients with a high risk to develop DN. Homocarnosine treatment can be expected to reduce CN1 activity toward carnosine, resulting in higher carnosine levels.

Keywords

Carnosine Homocarnosine Carnosinase CN1 Diabetic nephropathy 

Notes

Acknowledgments

We thank Prof. K. Michael Gibson for comments and critical reading of the manuscript. Part of this study was supported by the EU-funded specific-target project PREDICTIONS on the identification of risk factors for the development of diabetic nephropathy as well as grants by the Deutsche Forschungsgemeinschaft to M. Mack and J Zschocke (Ma2510/3-1 and Zs17/5-1).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Verena Peters
    • 1
    Email author
  • Moustafa Kebbewar
    • 2
  • Erwin W. Jansen
    • 3
  • Cornelis Jakobs
    • 3
  • Eva Riedl
    • 4
  • Hannes Koeppel
    • 4
  • Dirk Frey
    • 4
  • Katja Adelmann
    • 4
  • Kristina Klingbeil
    • 1
  • Matthias Mack
    • 5
  • Georg F. Hoffmann
    • 1
  • Bart Janssen
    • 2
  • Johannes Zschocke
    • 2
    • 6
  • Benito A. Yard
    • 4
  1. 1.Division of Metabolic DiseasesUniversity Children’s HospitalHeidelbergGermany
  2. 2.Institute of Human GeneticsUniversity Medical Centre HeidelbergHeidelbergGermany
  3. 3.Metabolic Unit, Department of Clinical ChemistryVU University Medical CentreAmsterdamThe Netherlands
  4. 4.5th Medical Clinic, University Medical Centre Mannheim, Medical Faculty MannheimHeidelberg UniversityHeidelbergGermany
  5. 5.Institute for Technical MicrobiologyMannheim University of Applied SciencesMannheimGermany
  6. 6.Divisions of Human Genetics and Clinical GeneticsMedical UniversityInnsbruckAustria

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