Disease relevance of CNDP1

• In addition, old age, male sex, and the presence of parapharyngeal disease were probably significant in predicting poor survival (ASR); CN1 was probably significant in predicting more local failures, and, the parapharyngeal disease and the intracranial extension for more distant metastases [1].
• A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans [2].
• Allelic variation in the CNDP1 gene and its lack of association with longevity and coronary heart disease [3].
• Crigler-Najjar syndrome types I and II (CN1 and CN2) are usually inherited as autosomal recessive conditions and are characterized by non-hemolytic unconjugated hyperbilirubinaemia [4].
• Finally, we determined the activity of the C3a- and C5a-inactivating enzyme, carboxypeptidase N1 (CN1), in plasma samples of patients both with and without hypersensitivity reactions [5].

High impact information on CNDP1

• A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy [6].
• Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1 [6].
• Three peptides, CN1, CN2, and CN4, which represent approximately 85% of the total amino acids of H315 were isolated and further characterized by electrophoresis and paper chromatography [7].
• Completion of the amino acid sequence of a Hong Kong influenza hemagglutinin heavy chain: sequence of cyanogen bromide fragment CN1 [8].
• CONCLUSION: European Americans homozygous for the 5-5 leucine repeat polymorphism in the CNDP1 gene are at significantly reduced risk for developing diabetic ESRD [2].

Chemical compound and disease context of CNDP1

• Oral BOF-A2 (Emitefur), a new derivative of 5-fluorouracil (5-FU) containing both 1-ethoxymethyl-5-FU (EMFU), a masked form of 5-FU, and 3-cyano-2,6-dihydroxypyridine (CNDP), an inhibitor of 5-FU degradation, was administered to 71 non-small cell lung cancer (NSCLC) patients in a multi-center phase II study [9].

Biological context of CNDP1

• RESULTS: Subjects with DM lacking nephropathy were significantly more likely to be homozygous for the 5-leucine repeat CNDP1 genotype (5-5), compared with those with DN-ESRD (P = 0.02) [2].
• The inhibitory effect of CNDP on the degradation of 5-FU in the tumor tissues was potent (IC50 3.9 x 10(-9) M) [10].
• All isolates were subtyped by PCR fingerprinting, using minisatellite (M13), and microsatellite [(GACA)4 and (GTG)5] specific primers, and RAPD analysis employing the combined primers 5SOR and CN1 [11].
• MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis [12].

Anatomical context of CNDP1

• Carnosine, a cytoprotective dipeptide found at very high concentrations in skeletal muscle, heart and brain, is cleaved in blood by serum carnosinase which is encoded by the CNDP1 gene [3].

Associations of CNDP1 with chemical compounds

• Elevated haemoglobin only interferes with CN1 measurements, and high bilirubin concentrations slightly alter the activity of both enzymes [13].
• The Michaelis-Menten constants are: CN1 4.59 +/- 0.03 mmol/l; CN2 37.26 +/- 3.49 mmol/l. CN2 can be inhibited by EDTA (76%), dimercaprolum (97%) and phenanthroline (98%) [13].
• Kininase I (carboxypeptidase N; EC 3.4.17.3) consists of carboxypeptidase N1 (CN1) and carboxypeptidase N2 (CN2); these two enzymes can be differentiated by their activities towards hippuryl-L-arginine and hippuryl-L-lysine, respectively [13].
• BOF-A2 is an anti-neoplastic agent newly synthesized from 1-ethoxymethyl-5-FU and 3-cyano-2,6-dihydroxypyridine (CNDP) [10].
• Elevations of CN1 and CN2 in the hyperthyroid state seem not to be related to underlying immunological processes but to the thyroid hormone excess itself [14].

Other interactions of CNDP1

• Two missing fragments, CN2 (82 residues) and CN3b1 (76 residues) were purified after breaking of the interpeptidic disulfide bridge and their complete sequence as well as that of the previously purified CN1 peptide (102 residues) are reported here [15].
• CN1 is the most severe form, associated with the absence of hepatic bilirubin-uridinediphosphoglucuronate glucuronosyltransferase (UGT1A1) activity [4].

Analytical, diagnostic and therapeutic context of CNDP1

• Sequence analysis showed that anserinase is a member of the M20A metallopeptidase subfamily in MEROPS peptidase database, to which 'serum' carnosinase (EC 3.4.13.20) and cytosolic nonspecific dipeptidase (EC 3.4.13.18, CNDP) belong [16].
• After oral administration of BOF-A2 at 15 mg/kg to Yoshida sarcoma-bearing rats, BOF-A2 was hydrolyzed to EM-FU, CNDP and 5-FU, and their maximum concentrations in the blood were 2000 ng/ml, 300 ng/ml and 40 ng/ml, respectively [17].

References