title: Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity.
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 microM homocarnosine lowered V (max) for carnosine from 440 to 356 pmol/min/microg and increased K (m) from 175 to 210 microM. The estimated K (i) for homocarnosine was higher (240 microM). 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.
authors.affiliation: Division of Metabolic Diseases, University Children's Hospital, Heidelberg, Germany. verena.peters@med.uni-heidelberg.de
authors.forename: Verena
authors.initials: V
authors.lastname: Peters
authors.forename: Moustafa
authors.initials: M
authors.lastname: Kebbewar
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Jansen
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Eva
authors.initials: E
authors.lastname: Riedl
authors.forename: Hannes
authors.initials: H
authors.lastname: Koeppel
authors.forename: Dirk
authors.initials: D
authors.lastname: Frey
authors.forename: Katja
authors.initials: K
authors.lastname: Adelmann
authors.forename: Kristina
authors.initials: K
authors.lastname: Klingbeil
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: Bart
authors.initials: B
authors.lastname: Janssen
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
mesh_terms: D000328:Adult; D000494:Allosteric Regulation; D000818:Animals; D015153:Blotting, Western; D002336:Carnosine / Q000031:analogs & derivatives* / Q000378:metabolism; D002648:Child; D004150:Dipeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D012016:Reference Values
chemical_list: C005038:homocarnosine; D002336:Carnosine; D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase