Institute of Biostructure and Bioimaging, CNR, viale A. Doria 6, 95125 Catania, Italy. francesco. bellia@cnr. it.
Department of Chemical Sciences, University of Catania, viale A. Doria 6, 95125 Catania, Italy
References: Chen, S.L., Marino, T., Fang, W.H., Russo, N., Himo, F., Peptide hydrolysis by the binuclear zinc enzyme aminopeptidase from Aeromonas proteolytica: A density functional theory study (2008) J. Phys. Chem. B, 112, pp. 2494-250
Hanson, H.T., Smith, E.L., Carnosinase: An enzyme of swine kidney (1949) J. Biol. Chem., 179, pp. 789-801
Lenney, J.F., Peppers, S.C., Kucera-Orallo, C.M., George, R.P., Characterization of human tissue carnosinase (1985) Biochem. J., 228, pp. 653-660
Jackson, M.C., Kucera, C.M., Lenney, J.F., Purification and properties of human serum carnosinase (1991) Clin. Chim. Acta, 196, pp. 193-205
Teufel, M., Saudek, V., Ledig, J.P., Bernhardt, A., Boularand, S., Carreau, A., Cairns, N.J., Duverger, D., Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase (2003) J. Biol. Chem., 278, pp. 6521-6531
Gulewitsch, W., Amiradzibi, S., Carnosine a new organic base from meat extracts (1900) Ber. Dtsch. Chem. Ges., 33, pp. 1902-1903
Bellia, F., Vecchio, G., Cuzzocrea, S., Calabrese, V., Rizzarelli, E., Neuroprotective features of carnosine in oxidative driven diseases (2011) Mol. Aspects Med., 32, pp. 258-266
Boldyrev, A.A., Aldini, G., Derave, W., Physiology and pathophysiology of carnosine (2013) Physiol. Rev., 93, pp. 1803-1845
Bellia, F., Calabrese, V., Guarino, F., Cavallaro, M., Cornelius, C., De Pinto, V., Rizzarelli, E., Carnosinase levels in aging brain: Redox state induction and cellular stress response (2009) Antioxid. Redox Signal., 11, pp. 2759-2775
Gautam, P., Nair, S.C., Gupta, M.K., Sharma, R., Polisetty, R.V., Uppin, M.S., Sundaram, C., Purohit, A.K., Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis (2012) PLoS One, 7, pp. e46153
Boldyrev, A.A., Severin, S.E., The histidine-containing dipeptides, carnosine and anserine: Distribution, properties and biological significance (1990) Adv. Enzym. Regul., 30, pp. 175-194
Neidle, A., Kandera, J., Carnosine-An olfactory bulb peptide (1974) Brain Res., 80, pp. 359-364
Horinishi, H., Grillo, M., Margolis, F.L., Purification and characterization of carnosine synthetase from mouse olfactory bulbs (1978) J. Neurochem., 31, pp. 909-919
Kalyankar, G.D., Meister, A., Enzymatic synthesis of carnosine and related beta-alanyl and gamma-aminobutyryl peptides (1959) J. Biol. Chem., 234, pp. 3210-3218
Hoffmann, A.M., Bakardjiev, A., Bauer, K., Carnosine-synthesis in cultures of rat glial cells is restricted to oligodendrocytes and carnosine uptake to astrocytes (1996) Neurosci. Lett., 215, pp. 29-32
Drozak, J., Veiga-Da-Cunha, M., Vertommen, D., Stroobant, V., Van Schaftingen, E., Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1) (2010) J. Biol. Chem., 285, pp. 9346-9356
Yamada, S., Tanaka, Y., Furuichi, M., Partial purification and characterization of histidine acetyltransferase in brain of Nile tilapia (Oreochromis niloticus) (1995) Biochim. Biophys. Acta, 1245, pp. 239-247
Baslow, M.H., Lenney, J.F., Alpha-N-acetyl-L-histidine amidohydrolase activity from the brain of the skipjack tuna Katsuwonus pelamis (1967) Can. J. Biochem., 45, pp. 337-340
Lenney, J.F., Baslow, M.H., Sugiyama, G.H., Similarity of tuna N-acetylhistidine deacetylase and cod fish anserinase (1978) Comp. Biochem. Physiol. B: Biochem. Mol. Biol., 61, pp. 253-258
Drozak, J., Chrobok, L., Poleszak, O., Jagielski, A.K., Derlacz, R., Molecular identification of carnosine N-methyltransferase as chicken histamine N-methyltransferase-like protein (HNMTLike) (2013) PLoS One, 8, pp. e64805
Gjessing, L.R., Lunde, H.A., Mørkrid, L., Lenney, J.F., Sjaastad, O., Inborn errors of carnosine and homocarnosine metabolism (1990) J. Neural Transm. Suppl., 29, pp. 91-106
Petroff, O.A.C., GABA and glutamate in the human brain (2002) Neuroscientist, 8, pp. 562-573
Petroff, O.A.C., Hyder, F., Rothman, D.L., Mattson, R.H., Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures (2001) Neurology, 56, pp. 709-715
Gil-Agusti, M., Esteve-Romero, J., Carda-Broch, S., Anserine and carnosine determination in meat samples by pure micellar liquid chromatography (2008) J. Chromatogr. A, 1189, pp. 444-450
Baguet, A., Reyngoudt, H., Pottier, A., Everaert, I., Callens, S., Achten, E., Derave, W., Carnosine loading and washout in human skeletal muscles (2009) J. Appl. Physiol., 106, pp. 837-842
Kim, H.J., Comparison of the carnosine and taurine contents of vastus lateralis of elderly Korean males, with impaired glucose tolerance, and young elite Korean swimmers (2009) Amino Acids, 36, pp. 359-363
Stuerenburg, H.J., Kunze, K., Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles (1999) Arch. Gerontol. Geriatr., 29, pp. 107-113
Tallon, M.J., Harris, R.C., Maffulli, N., Tarnopolsky, M.A., Carnosine taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects (2007) Biogerontology, 8, pp. 129-137
Harris, R.C., Tallon, M.J., Dunnett, M., Boobis, L., Coakley, J., Kim, H.J., Fallowfield, J.L., Wise, J.A., The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis (2006) Amino Acids, 30, pp. 279-289
Smith, E.C., The buffering of muscle in rigor
Protein, phosphate and carnosine (1938) J. Physiol., 92, pp. 336-343
Aruoma, O.I., Laughton, M.J., Halliwell, B., Carnosine homocarnosine and anserine: Could they act as antioxidants in vivo? (1989) Biochem. J., 264, pp. 863-869
Kohen, R., Misgav, R., Ginsburg, I., The SOD like activity of copper:carnosine, copper:anserine and copper:homocarnosine complexes (1991) Free Radic. Res. Commun., 12, pp. 179-185
Baran, E.J., Metal complexes of carnosine (2000) Biochemistry (Moscow), 65, pp. 789-797
Bonomo, R.P., Bruno, V., Conte, E., De Guidi, G., La Mendola, D., Maccarrone, G., Nicoletti, F., Vecchio, G., Potentiometric spectroscopic and antioxidant activity studies of SOD mimics containing carnosine (2003) Dalton Trans., pp. 4406-4415. , doi:10.1039/B308168K
Cuzzocrea, S., Genovese, T., Failla, M., Vecchio, G., Fruciano, M., Mazzon, E., Di Paola, R., Crimi, N., Protective effect of orally administered carnosine on bleomycin-induced lung injury (2007) Am. J. Physiol. Lung Cell. Mol. Physiol., 292, pp. L1095-L1104
Chuang, C.H., Hu, M.L., L-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1 (2008) Nutr. Cancer, 60, pp. 526-533
Hipkiss, A.R., Michaelis, J., Syrris, P., Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent (1995) FEBS Lett., 371, pp. 81-85
Hipkiss, A.R., Carnosine and protein carbonyl groups: A possible relationship (2000) Biochemistry (Moscow), 65, pp. 771-778
Lee, Y.T., Hsu, C.C., Lin, M.H., Liu, K.S., Yin, M.C., Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation (2005) Eur. J. Pharmacol., 513, pp. 145-150
Sauerhofer, S., Yuan, G., Braun, G.S., Deinzer, M., Neumaier, M., Gretz, N., Floege, J., Moeller, M.J., L-carnosine a substrate of carnosinase-1, influences glucose metabolism (2007) Diabetes, 56, pp. 2425-2432
Biffo, S., Delucia, R., Mulatero, B., Margolis, F., Fasolo, A., Carnosine-calcitonin gene-related peptide- and tyrosine hydroxylase-immunoreactivity in the mouse olfactory bulb following peripheral denervation (1990) Brain Res., 528, pp. 353-357
Bonfanti, L., Peretto, P., De Marchis, S., Fasolo, A., Carnosine-related dipeptides in the mammalian brain (1999) Prog. Neurobiol., 59, pp. 333-353
Xiang, J., Hu, Y., Smith, D.E., Keep, R.F., PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes (2006) Brain Res., 1122, pp. 18-23
Hipkiss, A.R., Glycation ageing and carnosine: Are carnivorous diets beneficial? (2005) Mech. Ageing Dev., 126, pp. 1034-1039
Huang, Y., Duan, J., Chen, H., Chen, M., Chen, G., Separation and determination of carnosine-related peptides using capillary electrophoresis with laser-induced fluorescence detection (2005) Electrophoresis, 26, pp. 593-599
Hipkiss, A.R., Could carnosine suppress zinc-mediated proteasome inhibition and neurodegeneration? Therapeutic potential of a non-toxic but non-patentable dipeptide (2005) Biogerontology, 6, pp. 147-149
La Mendola, D., Sortino, S., Vecchio, G., Rizzarelli, E., Synthesis of new carnosine derivatives of b-cyclodextrin and their hydroxyl radical scavenger ability (2002) Helv. Chim. Acta, 85, pp. 1633-1643
Fontana, M., Pinnen, F., Lucente, G., Pecci, L., Prevention of peroxynitrite-dependent damage by carnosine and related sulphonamido pseudodipeptides (2002) Cell. Mol. Life Sci., 59, pp. 546-551
Severina, I.S., Bussygina, O.G., Pyatakova, N.V., Carnosine as a regulator of soluble guanylate cyclase (2000) Biochemistry (Moscow), 65, pp. 783-788
Dukic-Stefanovic, S., Schinzel, R., Riederer, P., Munch, G., AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs? (2001) Biogerontology, 2, pp. 19-34
Pubill, D., Verdaguer, E., Sureda, F.X., Camins, A., Pallas, M., Camarasa, J., Escubedo, E., Carnosine prevents methamphetamine-induced gliosis but not dopamine terminal loss in rats (2002) Eur. J. Pharmacol., 448, pp. 165-168
Dobrota, D., Fedorova, T., Stvolinsky, S., Babusikova, E., Likavcanova, K., Drgova, A., Strapkova, A., Boldyrev, A., Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury: After-stroke-effect (2005) Neurochem. Res., 30, pp. 1283-1288
Stvolinsky, S., Kukley, M., Dobrota, D., Mezesova, V., Boldyrev, A., Carnosine protects rats under global ischemia (2000) Brain Res. Bull., 53, pp. 445-448
Tang, S.C., Arumugam, T.V., Cutler, R.G., Jo, D.G., Magnus, T., Chan, S.L., Mughal, M.R., Ouyang, X., Neuroprotective actions of a histidine analogue in models of ischemic stroke (2007) J. Neurochem., 101, pp. 729-736
Calabrese, V., Colombrita, C., Guagliano, E., Sapienza, M., Ravagna, A., Cardile, V., Scapagnini, G., Butterfield, D.A., Protective effect of carnosine during nitrosative stress in astroglial cell cultures (2005) Neurochem. Res., 30, pp. 797-807
Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D.A., Stella, A.M., Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity (2007) Nat. Rev. Neurosci., 8, pp. 766-775
Nicoletti, V.G., Santoro, A.M., Grasso, G., Vagliasindi, L.I., Giuffrida, M.L., Cuppari, C., Purrello, V.S., Rizzarelli, E., Carnosine interaction with nitric oxide and astroglial cell protection (2007) J. Neurosci. Res., 85, pp. 2239-2245
Preston, J.E., Hipkiss, A.R., Himsworth, D.T., Romero, I.A., Abbott, J.N., Toxic effects of beta-amyloid(25-35) on immortalised rat brain endothelial cell: Protection by carnosine, homocarnosine and beta-alanine (1998) Neurosci. Lett., 242, pp. 105-108
Attanasio, F., Convertino, M., Magno, A., Caflisch, A., Corazza, A., Haridas, H., Esposito, G., Milardi, D., Carnosine inhibits Abeta(42) aggregation by perturbing the H-bond network in and around the central hydrophobic cluster (2013) ChemBioChem, 14, pp. 583-592
Hipkiss, A.R., Preston, J.E., Himsworth, D.T., Worthington, V.C., Keown, M., Michaelis, J., Lawrence, J., Eagles, P.A., Pluripotent protective effects of carnosine, a naturally occurring dipeptide (1998) Ann. N. Y. Acad. Sci., 854, pp. 37-53
Fonteh, A.N., Harrington, R.J., Tsai, A., Liao, P., Harrington, M.G., Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects (2007) Amino Acids, 32, pp. 213-224
Jin, C.L., Yang, L.X., Wu, X.H., Li, Q., Ding, M.P., Fan, Y.Y., Zhang, W.P., Chen, Z., Effects of carnosine on amygdaloid-kindled seizures in Sprague-Dawley rats (2005) Neuroscience, 135, pp. 939-947
Pegova, A., Abe, H., Boldyrev, A., Hydrolysis of carnosine and related compounds by mammalian carnosinases (2000) Comp. Biochem. Physiol. B: Biochem. Mol. Biol., 127, pp. 443-446
Hou, W.C., Chen, H.J., Lin, Y.H., Antioxidant peptides with Angiotensin converting enzyme inhibitory activities and applications for Angiotensin converting enzyme purification (2003) J. Agric. Food Inf., 51, pp. 1706-1709
Aydogan, S., Yapislar, H., Artis, S., Aydogan, B., Impaired erythrocytes deformability in H(2)O(2)-induced oxidative stress: Protective effect of L-carnosine (2008) Clin. Hemorheol. Microcirc., 39, pp. 93-98
Janssen, B., Hohenadel, D., Brinkkoetter, P., Peters, V., Rind, N., Fischer, C., Rychlik, I., De Heer, E., Carnosine as a protective factor in diabetic nephropathy: Association with a leucine repeat of the carnosinase gene CNDP1 (2005) Diabetes, 54, pp. 2320-2327
Tanida, M., Shen, J., Kubomura, D., Nagai, K., Effects of anserine on the renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats (2010) Physiol. Res., 59, pp. 177-185
Kubomura, D., Matahira, Y., Nagai, K., Niijima, A., Effect of anserine ingestion on hyperglycemia and the autonomic nerves in rats and humans (2010) Nutr. Neurosci., 13, pp. 183-188
Suzuki, Y., Nakao, T., Maemura, H., Sato, M., Kamahara, K., Morimatsu, F., Takamatsu, K., Carnosine and anserine ingestion enhances contribution of nonbicarbonate buffering (2006) Med. Sci. Sports Exercise, 38, pp. 334-338
Szwergold, B.S., Carnosine and anserine act as effective transglycating agents in decomposition of aldose-derived Schiff bases (2005) Biochem. Biophys. Res. Commun., 336, pp. 36-41
Boldyrev, A., Bulygina, E., Leinsoo, T., Petrushanko, I., Tsubone, S., Abe, H., Protection of neuronal cells against reactive oxygen species by carnosine and related compounds (2004) Comp. Biochem. Physiol. B: Biochem. Mol. Biol., 137, pp. 81-88
Kang, J.H., Kim, K.S., Choi, S.Y., Kwon, H.Y., Won, M.H., Kang, T.C., Protective effects of carnosine, homocarnosine and anserine against peroxyl radical-mediated Cu, Zn-superoxide dismutase modification (2002) Biochim. Biophys. Acta, 1570, pp. 89-96
Aldini, G., Facino, R.M., Beretta, G., Carini, M., Carnosine and related dipeptides as quenchers of reactive carbonyl species: From structural studies to therapeutic perspectives (2005) BioFactors, 24, pp. 77-87
Min, J., Senut, M.C., Rajanikant, K., Greenberg, E., Bandagi, R., Zemke, D., Mousa, A., Gupta, R., Differential neuroprotective effects of carnosine, anserine, and N-acetyl carnosine against permanent focal ischemia (2008) J. Neurosci. Res., 86, pp. 2984-2991
Sadzuka, Y., Sonobe, T., Anserine induced advantage effects on the antitumor activity of doxorubicin (2007) Food Chem. Toxicol., 45, pp. 985-989
Shao, L., Li, Q.H., Tan, Z., L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts (2004) Biochem. Biophys. Res. Commun., 324, pp. 931-936
Boldyrev, A.A., Dupin, A.M., Bunin, A., Babizhaev, M.A., Severin, S.E., The antioxidative properties of carnosine, a natural histidine containing dipeptide (1987) Biochem. Int., 15, pp. 1105-1113
Babizhayev, M.A., Kasus-Jacobi, A., State of the art clinical efficacy and safety evaluation of N-acetylcarnosine dipeptide ophthalmic prodrug. Principles for the delivery, self-bioactivation, molecular targets and interaction with a highly evolved histidyl-hydrazide structure in the treatment and therapeutic management of a group of sight-threatening eye diseases (2009) Curr. Clin. Pharmacol., 4, pp. 4-37
Babizhayev, M.A., Yegorov, Y.E., Telomere attrition in lens epithelial cells - A target for N-acetylcarnosine therapy (2010) Front. Biosci., 15, pp. 934-956
Katayama, S., Nishizawa, K., Hirano, M., Yamamura, S., Momose, Y., Effect of polaprezinc on healing of acetic acid-induced stomatitis in hamsters (2000) J. Pharm. Pharm. Sci., 3, pp. 114-117
Matsukura, T., Tanaka, H., Applicability of zinc complex of L-carnosine for medical use (2000) Biochemistry (Moscow), 65, pp. 817-823
Ueda, K., Ueyama, T., Oka, M., Ito, T., Tsuruo, Y., Ichinose, M., Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - A new mechanism of gastric mucosal protection (2009) J. Pharmacol. Sci., 110, pp. 285-294
Odashima, M., Otaka, M., Jin, M., Konishi, N., Sato, T., Kato, S., Matsuhashi, T., Watanabe, S., Induction of a 72-kDa heat-shock protein in cultured rat gastric mucosal cells and rat gastric mucosa by zinc L-carnosine (2002) Dig. Dis. Sci., 47, pp. 2799-2804
Ohata, S., Moriyama, C., Yamashita, A., Nishida, T., Kusumoto, C., Mochida, S., Minami, Y., Inagaki, Y., Polaprezinc Protects Mice against Endotoxin Shock (2010) J. Clin. Biochem. Nutr., 46, pp. 234-243
Kalmar, B., Greensmith, L., Induction of heat shock proteins for protection against oxidative stress (2009) Adv. Drug Del. Rev., 61, pp. 310-318
Corona, C., Frazzini, V., Silvestri, E., Lattanzio, R., La Sorda, R., Piantelli, M., Canzoniero, L.M., Sensi, S.L., Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice (2011) PLoS One, 6, pp. e17971
Di Paola, R., Impellizzeri, D., Salinaro, A.T., Mazzon, E., Bellia, F., Cavallaro, M., Cornelius, C., Rizzarelli, E., Administration of carnosine in the treatment of acute spinal cord injury (2011) Biochem. Pharmacol., 82, pp. 1478-1489
Barnham, K.J., Bush, A.I., Metals in Alzheimer's and Parkinson's diseases (2008) Curr. Opin. Chem. Biol., 12, pp. 222-228
Di Donato, M., Hsu, H.F., Narindrasorasak, S., Que Jr., L., Sarkar, B., Copper-induced conformational changes in the N-terminal domain of the Wilson disease copper-transporting ATPase (2000) Biochemistry (Moscow), 39, pp. 1890-1896
Fu, Q., Dai, H., Hu, W., Fan, Y., Shen, Y., Zhang, W., Chen, Z., Carnosine protects against Abeta42-induced neurotoxicity in differentiated rat PC12 cells (2008) Cell. Mol. Neurobiol., 28, pp. 307-316
Trombley, P.Q., Horning, M.S., Blakemore, L.J., Interactions between carnosine and zinc and copper: Implications for neuromodulation and neuroprotection (2000) Biochemistry (Moscow), 65, pp. 807-816
Lenney, J.F., Specificity and distribution of mammalian carnosinase (1976) Biochim. Biophys. Acta, 429, pp. 214-219
Lenney, J.F., Kan, S.C., Siu, K., Sugiyama, G.H., Homocarnosinase: A hog kidney dipeptidase with a broader specificity than carnosinase (1977) Arch. Biochem. Biophys., 184, pp. 257-266
Rosenberg, A., The activation of carnosinase by divalent metal ions (1960) Biochim. Biophys. Acta, 45, pp. 297-316
Rosenberg, A., Purification and some properties of carnosinase of swine kidney (1960) Arch. Biochem. Biophys., 88, pp. 83-93
Wolos, A., Piekarska, K., Glogowski, J., Konieczka, I., Two molecular forms of swine kidney carnosinase (1978) Int. J. Biochem., 9, pp. 57-62
Margolis, F.L., Grillo, M., Brown, C.E., Enzymatic and immunological evidence for two forms of carnosinase in the mouse (1979) Biochim. Biophys. Acta, 570, pp. 311-323
Kunze, N., Kleinkauf, H., Bauer, K., Characterization of two carnosine-degrading enzymes from rat brain. Partial purification and characterization of a carnosinase and a beta-alanyl-arginine hydrolase (1986) Eur. J. Biochem., 160, pp. 605-613
Lenney, J.F., Human cytosolic carnosinase: Evidence of identity with prolinase, a non-specific dipeptidase (1990) Biol. Chem. Hoppe-Seyler, 371, pp. 167-171
Perry, T.L., Hansen, S., Love, D.L., Serum-carnosinase deficiency in carnosinaemia (1968) Lancet, 1, pp. 1229-1230
Zoch, E., Muller, H., Demonstration and determination of earnosinase activity of the human placenta (1971) Enzymologia, 40, pp. 199-208
Lenney, J.F., George, R.P., Weiss, A.M., Kucera, C.M., Chan, P.W., Rinzler, G.S., Human serum carnosinase: Characterization, distinction from cellular carnosinase, and activation by cadmium (1982) Clin. Chim. Acta, 123, pp. 221-231
Otani, H., Okumura, N., Hashida-Okumura, A., Nagai, K., Identification and characterization of a mouse dipeptidase that hydrolyzes L-carnosine (2005) J. Biochem., 137, pp. 167-175
Murphey, W.H., Patchen, L., Lindmark, D.G., Carnosinase: A fluorometric assay and demonstration of two electrophoretic forms in human tissue extracts (1972) Clin. Chim. Acta, 42, pp. 309-314
Pandya, V., Ekka, M.K., Dutta, R.K., Kumaran, S., Mass spectrometry assay for studying kinetic properties of dipeptidases: Characterization of human and yeast dipeptidases (2011) Anal. Biochem., 418, pp. 134-142
Bando, K., Shimotsuji, T., Toyoshima, H., Fluorometric assay of human serum carnosinase activity in normal children, adults and patients with myopathy (1984) Ann. Clin. Biochem., 21, pp. 510-514
Jones, N.R., The free amino acids of fish
1-methylhistidine and beta-alanine liberation by skeletal muscle anserinase of codling (Gadus callarias) (1955) Biochem. J., 60, pp. 81-87
Chang, C.Y., Hsieh, Y.C., Wang, T.Y., Chen, Y.C., Wang, Y.K., Chiang, T.W., Chen, Y.J., Wu, T.K., Crystal structure and mutational analysis of aminoacylhistidine dipeptidase from Vibrio alginolyticus reveal a new architecture of M20 metallopeptidases (2010) J. Biol. Chem., 285, pp. 39500-39510
Jozic, D., Bourenkow, G., Bartunik, H., Scholze, H., Dive, V., Henrich, B., Huber, R., Maskos, K., Crystal structure of the dinuclear zinc aminopeptidase PepV from Lactobacillus delbrueckii unravels its preference for dipeptides (2002) Structure, 10, pp. 1097-1106
Rowsell, S., Pauptit, R.A., Tucker, A.D., Melton, R.G., Blow, D.M., Brick, P., Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy (1997) Structure, 5, pp. 337-347
Unno, H., Yamashita, T., Ujita, S., Okumura, N., Otani, H., Okumura, A., Nagai, K., Kusunoki, M., Structural basis for substrate recognition and hydrolysis by mouse carnosinase CN2 (2008) J. Biol. Chem., 283, pp. 27289-27299
Partmann, W., Eine Carnosine spaltende Enzymaktivität im Skelettmuskel des Aales (1976) Arch. Fisch Wiss., 27, pp. 55-62
Perez, B.S., Jones, N.R., Effects of tetracycline antibiotics on the products of anserinase action in chill stored haddock (Gadus aeglefinus) muscle (1962) J. Food Sci., 27, pp. 69-72
Oku, T., Ando, S., Tsai, H.C., Yamashita, Y., Ueno, H., Shiozaki, K., Nishi, R., Yamada, S., Purification and identification of two carnosine-cleaving enzymes, carnosine dipeptidase i and Xaa-methyl-His dipeptidase, from Japanese eel (Anguilla japonica) (2012) Biochimie, 94, pp. 1281-1290
Vongerichten, K.F., Klein, J.R., Matern, H., Plapp, R., Cloning and nucleotide sequence analysis of pepV, a carnosinase gene from Lactobacillus delbrueckii subsp. Lactis DSM 7290, and partial characterization of the enzyme (1994) Microbiology, 140, pp. 2591-2600
Chevrier, B., Schalk, C., D'Orchymont, H., Rondeau, J.M., Moras, D., Tarnus, C., Crystal structure of Aeromonas proteolytica aminopeptidase: A prototypical member of the co-catalytic zinc enzyme family (1994) Structure, 2, pp. 283-291
Greenblatt, H.M., Almog, O., Maras, B., Spungin-Bialik, A., Barra, D., Blumberg, S., Shoham, G., Streptomyces griseus aminopeptidase: X-ray crystallographic structure at 1.75 A resolution (1997) J. Mol. Biol., 265, pp. 620-636
Hakansson, K., Miller, C.G., Structure of peptidase T from Salmonella typhimurium (2002) Eur. J. Biochem., 269, pp. 443-450
Lindner, H.A., Lunin, V.V., Alary, A., Hecker, R., Cygler, M., Menard, R., Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family (2003) J. Biol. Chem., 278, pp. 44496-44504
Lundgren, S., Gojkovic, Z., Piskur, J., Dobritzsch, D., Yeast beta-alanine synthase shares a structural scaffold and origin with dizinc-dependent exopeptidases (2003) J. Biol. Chem., 278, pp. 51851-51862
Rawlings, N.D., Barrett, A.J., Evolutionary families of metallopeptidases (1995) Methods Enzymol., 248, pp. 183-228
Bayliss, M.E., Prescott, J.M., Modified activity of Aeromonas aminopeptidase: Metal ion substitutions and role of substrates (1986) Biochemistry (Moscow), 25, pp. 8113-8117
Vistoli, G., Carini, M., Aldini, G., Transforming dietary peptides in promising lead compounds: The case of bioavailable carnosine analogs (2012) Amino Acids, 43, pp. 111-126
Vistoli, G., Pedretti, A., Cattaneo, M., Aldini, G., Testa, B., Homology modeling of human serum carnosinase, a potential medicinal target, and MD simulations of its allosteric activation by citrate (2006) J. Med. Chem., 49, pp. 3269-3277
Cohen, M., Hartlage, P.L., Krawiecki, N., Serum carnosinase deficiency: A non-disabling phenotype? (1985) J. Ment. Defic. Res., 29, pp. 383-389
Lunde, H.A., Gjessing, L.R., Sjaastad, O., Homocarnosinosis: Influence of dietary restriction of histidine (1986) Neurochem. Res., 11, pp. 825-838
Balion, C.M., Benson, C., Raina, P.S., Papaioannou, A., Patterson, C., Ismaila, A.S., Brain type carnosinase in dementia: A pilot study (2007) BMC Neurol., 7, p. 38
Butterworth, R.J., Wassif, W.S., Sherwood, R.A., Gerges, A., Poyser, K.H., Garthwaite, J., Peters, T.J., Bath, P.M.W., Serum neuron-specific enolase, carnosinase, and their ratio in acute stroke: An enzymatic test for predicting outcome? (1996) Stroke, 27, pp. 2064-2068
Licker, V., Côte, M., Lobrinus, J.A., Rodrigo, N., Kövari, E., Hochstrasser, D.F., Turck, N., Burkhard, P.R., Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in Parkinson's disease (2012) J. Proteomics, 75, pp. 4656-4667
Schoen, P., Everts, H., De Boer, T., Van Oeveren, W., Serum carnosinase activity in plasma and serum: Validation of a method and values in cardiopulmonary bypass surgery (2003) Clin. Chem., 49, pp. 1930-1932
Holdenrieder, S., Lütjohann, D., Geiger, S., Von Bergmann, K., Stieber, P., Hamann, G.F., Does brain specific 24S-hydroxycholesterol in plasma indicate the disruption of the blood-brain barrier in patients with ischemic stroke? (2004) Neurosci. Lett., 368, pp. 201-204
Kirk, J., Plumb, J., Mirakhur, M., McQuaid, S., Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination (2003) J. Pathol., 201, pp. 319-327
Skoog, I., Wallin, A., Fredman, P., Hesse, C., Aevarsson, O., Karlsson, I., Gottfries, C.G., Blennow, K., A population study on blood-brain barrier function in 85-year-olds: Relation to Alzheimer's disease and vascular dementia (1998) Neurology, 50, pp. 966-971
Kumar-Singh, S., Pirici, D., McGowan, E., Serneels, S., Ceuterick, C., Hardy, J., Duff, K., Van Broeckhoven, C., Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls (2005) Am. J. Pathol., 167, pp. 527-543
Willi, S.M., Zhang, Y., Hill, J.B., Phelan, M.C., Michaelis, R.C., Holden, K.R., A deletion in the long arm of chromosome 18 in a child with serum carnosinase deficiency (1997) Pediatr. Res., 41, pp. 210-213
Lee, J.H., Mayeux, R., Mayo, D., Mo, J., Santana, V., Williamson, J., Flaquer, A., Estevez, P., Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics (2004) Mol. Psychiatry, 9, pp. 1042-1051
Munzar, M., Levy, S., Rush, R., Averback, P., Clinical study of a urinary competitve ELISA for neural thread protein in Alzheimer disease (2002) Neurol. Clin. Neurophysiol., 2002, pp. 2-8
Larson, E.B., Wang, L., Bowen, J.D., McCormick, W.C., Teri, L., Crane, P., Kukull, W., Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older (2006) Ann. Intern. Med., 144, pp. 73-81
Vionnet, N., Tregouet, D., Kazeem, G., Gut, I., Groop, P.H., Tarnow, L., Parving, H.H., Farrall, M., Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: Strongest evidence for association with a variant in the promoter region of the adiponectin gene (2006) Diabetes, 55, pp. 3166-3174
Freedman, B.I., Hicks, P.J., Sale, M.M., Pierson, E.D., Langefeld, C.D., Rich, S.S., Xu, J., Yard, B.A., A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans (2007) Nephrol. Dial. Transplant., 22, pp. 1131-1135
Riedl, E., Koeppel, H., Brinkkoetter, P., Sternik, P., Steinbeisser, H., Sauerhoefer, S., Janssen, B., Yard, B.A., A CTG polymorphism in the CNDP1 gene determines the secretion of serum carnosinase in Cos-7-transfected cells (2007) Diabetes, 56, pp. 2410-2413
Iyengar, S.K., Freedman, B.I., Sedor, J.R., Mining the genome for susceptibility to diabetic nephropathy: The role of large-scale studies and consortia (2007) Semin. Nephrol., 27, pp. 208-222
Wanic, K., Placha, G., Dunn, J., Smiles, A., Warram, J.H., Krolewski, A.S., Exclusion of polymorphisms in carnosinase genes (CNDP1 and CNDP2) as a cause of diabetic nephropathy in type 1 diabetes: Results of large case-control and follow-up studies (2008) Diabetes, 57, pp. 2547-2551
McDonough, C.W., Hicks, P.J., Lu, L., Langefeld, C.D., Freedman, B.I., Bowden, D.W., The influence of carnosinase gene polymorphisms on diabetic nephropathy risk in African-Americans (2009) Hum. Genet., 126, pp. 265-275
Mooyaart, A.L., Zutinic, A., Bakker, S.J.L., Grootendorst, D.C., Kleefstra, N., Van Valkengoed, I.G.M., Böhringer, S., Bruijn, J.A., Association between CNDP1 genotype and diabetic nephropathy is sex specific (2010) Diabetes, 59, pp. 1555-1559
Ahluwalia, T.S., Lindholm, E., Groop, L.C., Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes (2011) Diabetologia, 54, pp. 2295-2302
Chakkera, H.A., Hanson, R.L., Kobes, S., Millis, M.P., Nelson, R.G., Knowler, W.C., Distefano, J.K., Association of variants in the carnosine peptidase 1 gene (CNDP1) with diabetic nephropathy in American Indians (2011) Mol. Genet. Metab., 103, pp. 185-190
Everaert, I., Mooyaart, A., Baguet, A., Zutinic, A., Baelde, H., Achten, E., Taes, Y., Derave, W., Vegetarianism female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans (2011) Amino Acids, 40, pp. 1221-1229
Peters, V., Jansen, E.E.W., Jakobs, C., Riedl, E., Janssen, B., Yard, B.A., Wedel, J., Gotthardt, D., Anserine inhibits carnosine degradation but in human serum carnosinase (CN1) is not correlated with histidine dipeptide concentration (2011) Clin. Chim. Acta, 412, pp. 263-267
Peters, V., Schmitt, C.P., Zschocke, J., Gross, M.L., Brismar, K., Forsberg, E., Carnosine treatment largely prevents alterations of renal carnosine metabolism in diabetic mice (2012) Amino Acids, 42, pp. 2411-2416
McManus, I.R., Enzymic synthesis of anserine in skeletal muscle by N-methylation of carnosine (1962) J. Biol. Chem., 237, pp. 1207-1211
Bossy-Wetzel, E., Schwarzenbacher, R., Lipton, S.A., Molecular pathways to neurodegeneration (2004) Nat. Med., 10 (SUPPL.), pp. S2-S9
Blennow, K., Hampel, H., Weiner, M., Zetterberg, H., Cerebrospinal fluid and plasma biomarkers in Alzheimer disease (2010) Nat. Rev. Neurol., 6, pp. 131-144
Hu, Y., Hosseini, A., Kauwe, J.S.K., Gross, J., Cairns, N.J., Goate, A.M., Fagan, A.M., Holtzman, D.M., Identification and validation of novel CSF biomarkers for early stages of Alzheimer's disease (2007) Proteomics Clin. Appl., 1, pp. 1373-1384
Perrin, R.J., Craig-Schapiro, R., Malone, J.P., Shah, A.R., Gilmore, P., Davis, A.E., Roe, C.M., Galasko, D.R., Identification and validation of novel cerebrospinal fluid biomarkers for staging early alzheimer's disease (2011) PLoS One, 6, pp. e16032
Renner, C., Zemitzsch, N., Fuchs, B., Geiger, K.D., Hermes, M., Hengstler, J., Gebhardt, R., Gaunitz, F., Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model (2010) Mol. Cancer, 9, p. 2
Pahari, D.R., Gu, Y.J., Van Oeveren, W., El-Essawi, A., Harringer, W., Brouwer, R.M., Effect of minimized perfusion circuit on brain injury markers carnosinase and brain-type fatty binding protein in coronary artery bypass grafting patients (2013) Artif. Organs, 37, pp. 128-135
Sale, C., Artioli, G.G., Gualano, B., Saunders, B., Hobson, R.M., Harris, R.C., Carnosine: From exercise performance to health (2013) Amino Acids, 44, pp. 1477-1491
Derave, W., Everaert, I., Beeckman, S., Baguet, A., Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training (2010) Sports Med., 40, pp. 247-263
Grasso, G.I., Bellia, F., Arena, G., Vecchio, G., Rizzarelli, E., Noncovalent interaction-driven stereoselectivity of copper(II) complexes with cyclodextrin derivatives of L- and D-carnosine (2011) Inorg. Chem., 50, pp. 4917-4924
Grasso, G.I., Arena, G., Bellia, F., Maccarrone, G., Parrinello, M., Pietropaolo, A., Vecchio, G., Rizzarelli, E., Intramolecular weak interactions in the thermodynamic stereoselectivity of copper(II) complexes with carnosine-trehalose conjugates (2011) Chem. Eur. J., 17, pp. 9448-9455
Lanza, V., Bellia, F., D'Agata, R., Grasso, G., Rizzarelli, E., Vecchio, G., New glycoside derivatives of carnosine and analogs resistant to carnosinase hydrolysis: Synthesis and characterization of their copper(II) complexes (2011) J. Inorg. Biochem., 105, pp. 181-188
Stvolinsky, S.L., Bulygina, E.R., Fedorova, T.N., Meguro, K., Sato, T., Tyulina, O.V., Abe, H., Boldyrev, A.A., Biological activity of novel synthetic derivatives of carnosine (2010) Cell. Mol. Neurobiol., 30, pp. 395-404
Astete, C.E., Songe Meador, D., Spivak, D., Sabliov, C., Synthesis of vitamin E-carnosine (VECAR): New antioxidant molecule with potential application in atherosclerosis (2013) Synth. Commun., 43, pp. 1299-1313
Sozio, P., Iannitelli, A., Cerasa, L.S., Cacciatore, I., Cornacchia, C., Giorgioni, G., Ricciutelli, M., Di Stefano, A., New L-dopa codrugs as potential antiparkinson agents (2008) Arch. Pharm., 341, pp. 412-417
Nativi, C., Gualdani, R., Dragoni, E., Di Cesare Mannelli, L., Sostegni, S., Norcini, M., Gabrielli, G., Francesconi, O., A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain Sci. Rep., 2013, p. 3. , doi:10.1038/srep02005
Saada, M.C., Montero, J.L., Vullo, D., Scozzafava, A., Winum, J.Y., Supuran, C.T., Carbonic anhydrase activators: Gold nanoparticles coated with derivatized histamine, histidine, and carnosine show enhanced activatory effects on several mammalian isoforms (2011) J. Med. Chem., 54, pp. 1170-1177
Bellia, F., Oliveri, V., Rizzarelli, E., Vecchio, G., New derivative of carnosine for nanoparticle assemblies (2013) Eur. J. Med. Chem., 70, pp. 225-232
Bertinaria, M., Rolando, B., Giorgis, M., Montanaro, G., Guglielmo, S., Buonsanti, M.F., Carabelli, V., Fruttero, R., Synthesis, physicochemical characterization, and biological activities of new carnosine derivatives stable in human serum as potential neuroprotective agents (2011) J. Med. Chem., 54, pp. 611-621
Supuran, C.T., Briganti, F., Tilli, S., Chegwidden, W.R., Scozzafava, A., Carbonic anhydrase inhibitors: Sulfonamides as antitumor agents? (2001) Biorg. Med. Chem., 9, pp. 703-714
Nielsen, C.U., Supuran, C.T., Scozzafava, A., Frokjaer, S., Steffansen, B., Brodin, B., Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonylureido-carnosine in a human epithelial cell line (2002) Pharm. Res., 19, pp. 1337-1344
Vistoli, G., Orioli, M., Pedretti, A., Regazzoni, L., Canevotti, R., Negrisoli, G., Carini, M., Aldini, G., Design synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species (2009) ChemMedChem, 4, pp. 967-975
Orioli, M., Vistoli, G., Regazzoni, L., Pedretti, A., Lapolla, A., Rossoni, G., Canevotti, R., Carini, M., Design, synthesis, ADME properties, and pharmacological activities of beta-alanyl-D-histidine (D-carnosine) prodrugs with improved bioavailability (2011) ChemMedChem, 6, pp. 1269-1282
Amorini, A.M., Bellia, F., Di Pietro, V., Giardina, B., La Mendola, D., Lazzarino, G., Sortino, S., Vecchio, G., Synthesis and antioxidant activity of new homocarnosine β-cyclodextrin conjugates (2007) Eur. J. Med. Chem., 42, pp. 910-920
Bellia, F., Amorini, A.M., La Mendola, D., Vecchio, G., Tavazzi, B., Giardina, B., Di Pietro, V., Rizzarelli, E., New glycosidic derivatives of histidine-containing dipeptides with antioxidant properties and resistant to carnosinase activity (2008) Eur. J. Med. Chem., 43, pp. 373-380
Bellia, F., La Mendola, D., Maccarrone, G., Mineo, P., Vitalini, D., Scamporrino, E., Sortino, S., Rizzarelli, E., Copper(II) complexes with β-cyclodextrin-homocarnosine conjugates and their antioxidant activity (2007) Inorg. Chim. Acta, 360, pp. 945-954
Carnosinases, Their Substrates And Diseases
Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (-alanyl-L-histidine) and homocarnosine (-aminobutyryl-L- histidine). Alterations of serum carnosinase (CN1) activity has been associated with several pathological conditions, such as neurological disorders, chronic diseases and cancer. For this reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF) has been questioned. The hydrolysis of imidazolerelated dipeptides in prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases like PepD (EC 3. 4. 13. 3), PepV (EC 3. 4. 13. 19) and anserinase (EC 3. 4. 13. 5). The review deals with the structure and function of this class of enzymes in physiological and pathological conditions. The main substrates of these enzymes, i. e., carnosine, homocarnosine and anserine (-alanyl-3-methyl-L-histidine) will also be described. 2014 by the authors; licensee MDPI, Basel, Switzerland