Identification and characterization of a mouse dipeptidase that hydrolyzes L-carnosine.
L-Carnosine is a bioactive dipeptide present in mammalian tissues including the central nervous system. We have recently shown that L-carnosine is involved in the regulation of energy homeostasis through the autonomic nervous system, but the mechanisms for its biosynthesis and degradation have not yet been fully elucidated. Here we report the biochemical and immunohistochemical characterization of a mammalian protein that has a 17% overall amino acid sequence homology with a Lactobacilus carnosinase, PepV. A recombinant protein expressed in E. coli has the enzymatic ability to digest L-carnosine and various other dipeptides, and this activity is inhibited by bestatin. It requires Mn2+ for enzymatic activity and its effect is reversible. Immunohistochemical analysis showed that a few neuronal populations express this protein at very high levels. It is highly expressed in the parafascicular nucleus of the thalamus, tuberomammillary nucleus of the hypothalamus and the mitral cell layer of the olfactory bulb. In addition, neuronal processes, but not cell bodies, are stained in the striatum. In all these areas, the protein did not colocalize with the glial fibrilary acidic protein. These results suggest that a peptidase that digests L-carnosine is enriched in several specific neuronal populations in the central nervous system.
Otani
Hiroto
H
Division of Protein Metabolism, Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871.
Okumura
Nobuaki
N
Hashida-Okumura
Akiko
A
Nagai
Katsuya
K
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002336:Carnosine / Q000378:metabolism*; D004150:Dipeptidases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology; D010802:Phylogeny; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D002336:Carnosine; D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase