Disease relevance of CPA6

• Using radioimmunoassays specific for essential processing sites of human progastrin in combination with chromatography before and after cleavage with trypsin and carboxypeptidase B, we have examined antral biopsy specimens and serum from 10 hypergastrinemic patients with fundic atrophic gastritis and 7 normal control subjects [1].
• These effects were abolished by cleavage of the COOH-terminal arginine by carboxypeptidase B. The magnitude of C3a-induced tachycardia correlated with the amount of endogenous cardiac histamine released into the coronary effluent [2].
• Activation peptide of carboxypeptidase B in serum and urine in acute pancreatitis [3].
• Nine proteins specified by Kunjin virus were labelled with [3H]lysine and digested with carboxypeptidase B which specifically cleaves carboxy-terminal Lys or Arg [4].
• The added arginine tail could be specifically removed by carboxypeptidase B. When E. coli lyzate containing the mutant lectin was applied to the column more than 10-fold enrichment of the mutant lectin was attained [5].

Psychiatry related information on CPA6

• Expression and distribution of carboxypeptidase B in the hippocampal subregions of normal and Alzheimer's disease brain [6].

High impact information on CPA6

• To examine whether T cells can produce met-enkephalin precursor peptides, T cell conditioned media were treated with trypsin and carboxypeptidase-B, which is known to release met-enkephalin from the propeptide [7].
• We have optimized conditions for measurement of immunoreactive Met-enkephalin in plasma and for generation by trypsin and carboxypeptidase B of much greater amounts of total peptidase-derivable Met-enkephalin in plasma of rats, dogs, and humans [8].
• In contrast, clot lysis by t-PA was unaffected by plasmin pretreatment and little affected by carboxypeptidase B treatment of the fibrin substrate [9].
• Promotion by plasmin was nullified by a subsequent treatment of the clot with carboxypeptidase B, indicating that the plasmin effect was related to the exposure of carboxy terminal lysine residues on fibrin [9].
• The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes [10].

Chemical compound and disease context of CPA6

• The acute effects of bisoprolol 10 mg i.v., a new beta1-selective adrenoceptor antagonist, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), para-aminohippuric acid clearance (CPAH), sodium clearance, urine volume and plasma renin activity (PRA), were studied in 6 patients with essential hypertension [11].
• However, in a patient who developed a captopril-induced nephrotic syndrome, GFR dropped to 56% and CPAH to 50% of the control values [12].
• The structure of histargin, an inhibitor of carboxypeptidase B, produced by Streptomyces roseoviridis MF118-A5 strain, has been defined as N-[(S)-1-carboxy-4-guanidinobutyl]-N'-[(S)-1-carboxy-2-(imidazol-4 -yl) ethyl]ethylenediamine, by spectral analysis and chemical synthesis [13].
• The properties and lysosomal distribution of the enzyme indicated that it was a carboxypeptidase B. Substrate affinity, thermolability, pH stability, the fall and rise in activity with subculture, the cyclical pattern of activity through serial passage and the level of activity were similar for the control and cystic fibrosis enzyme [14].
• Carboxypeptidase B-like activity and C3 in cystic fibrosis [15].

Biological context of CPA6

• The CP on chromosome 8 is predicted to have a CPA-like specificity for C-terminal hydrophobic residues and was named CPA6 [16].
• RESULTS: A carboxypeptidase gene (CPAH) was directly interrupted between the first and second exons in a patient with DURS who carried a de novo reciprocal balanced translocation t(6;8)(q26;q13) involving the DURS1 region on chromosome arm 8q13 [17].
• The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged [18].
• Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme that after activation down-regulates fibrinolysis [19].
• Equilibrium binding analysis and [Lys]Pg activation kinetics with wild-type SK, carboxypeptidase B-treated SK, and a COOH-terminal Lys(414) deletion mutant (SKDeltaK414) demonstrated a critical role for Lys(414) in the enhancement of [Lys]Pg and [Lys]Pm binding and conformational [Lys]Pg activation [20].

Anatomical context of CPA6

• Bone marrow supernatant factor is stable to heat (100 degrees for 10 min) and trypsin digestion, but is sensitive to carboxypeptidase B digestion [21].
• Further, removal of the carboxyl terminal arginine by carboxypeptidase B abolished activity on the ileum but not in the skin [22].
• A membrane-bound neutral carboxypeptidase B-like enzyme was solubilized from human placental microvilli with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) and purified to homogeneity by ion-exchange chromatography and affinity chromatography on arginine-Sepharose [23].
• We treated U937 cells with CpB, then subjected membrane fractions to two-dimensional gel electrophoresis followed by ligand blotting with (125)I-plasminogen [24].
• An islet carboxypeptidase B-like enzyme (CP B) has been identified and characterized in secretory granules of anglerfish islets [25].

Associations of CPA6 with chemical compounds

• Release of carboxyl-terminal arginine residue by carboxypeptidase B, converting C3a into des-Arg77-C3a, did not alter the inhibitory effect displayed by this fragment [26].
• When tested with hippurylarginine, hippurylargininic acid, benzoylalanyllysine, or bradykinin, the Mr 48,000 subunit was as active as the intact enzyme and was easily distinguished from human pancreatic carboxypeptidase B (EC 3.4.17.2) [27].
• The variant COOH terminus ends with the dibasic sequence Arg-Lys that is apparently removed through stepwise cleavage by serum carboxypeptidase B to yield several forms of circulating albumin [28].
• The resulting benzyloxycarbonyl derivatives of isoglutaminylarginine methyl ester and isoasparaginylarginine methyl ester were treated with trypsin for removal of the ester groups and then with porcine pancreatic carboxypeptidase B for liberation of arginine and the original benzyloxycarbonyl derivatives of isoglutamine and isoasparagine [29].
• The immunochemical detection of these FPB-related peptides should provide useful information concerning the action of proteolytic enzymes, such as plasmin on the NH2-terminal segment of the B beta-chain of fibrinogen, and of carboxypeptidase-B on free FPB, in human plasma [30].

Physical interactions of CPA6

• Experiments involving affinity chromatography on immobilized plasminogen columns and the concomitant use of plasmin and carboxypeptidase B indicate that the COOH-terminal lysine residues formed by plasmin-catalyzed cleavage of fibrinogen are essential for the high-affinity binding of the resulting cleavage products to plasminogen [31].

Enzymatic interactions of CPA6

• Addition of a specific carboxypeptidase B inhibitor (Plummers inhibitor) could partly prevent the deletion of Lys-58 from cleaved beta 2-microglobulin, whereby Lys58-cleaved beta 2-microglobulin was obtained [32].

Regulatory relationships of CPA6

• Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described plasma zymogen that can be activated by thrombin to an enzyme with carboxypeptidase B-like activity [33].
• The incubation of AIIt with a 1/400 molar ratio of carboxypeptidase B for periods as short as 2 min resulted in a significant loss in AIIt-stimulated plasminogen activation [34].

Other interactions of CPA6

• In this study, we examined the effect of thrombin-activable fibrinolysis inhibitor (TAFI), a latent carboxypeptidase B (CPB)-like enzyme, on the stimulatory activity of (DD)E [35].
• The cap is subsequently removed with carboxypeptidase B to yield mature biologically active ISG15 capable of stoichiometric ATP-dependent thiolester formation with its human UbE1L activating enzyme [36].
• Detroit 562 cells preferentially bound to Lys-plasminogen and this binding was inhibited in the presence of a lysine analog, epsilon-aminocaproic acid and by carboxypeptidase-B treatment suggesting that the C-terminal lysine residue of the putative pharyngeal cell receptor(s) may play an important role in plasminogen-binding [37].
• To investigate the effect of basic carboxypeptidases on fibrinolysis under conditions of constant carboxypeptidase activity, we employed pancreatic carboxypeptidase B (CPB), a homologous, stable basic carboxypeptidase, as a surrogate for TAFIa [38].
• Complement C4 allotyping was achieved by agarose gel electrophoresis of neuraminidase/carboxypeptidase B digested plasma samples followed by immunofixation and staining [39].

Analytical, diagnostic and therapeutic context of CPA6

• Insulin infusion did not affect Cin, increased CPAH (p < 0.05) and, consequently, lowered the filtration fraction (p < 0.01) in both groups [40].
• New bands appearing at pI 6.65 and 6.75 after treatment of sMi-CK with carboxypeptidase B were found to be delysined forms. sMi-CK reacted with anti-sMi-CK antibodies, and the immune complexes were focused at pI 5 [41].
• Donor CPAH prior to donation was significantly correlated with the renal allograft function of the recipients but not with the recipient ranked MAP at follow-up [42].
• Studies were performed with IPS (mean airway pressure 12-15 cm H2O), continuous positive airway pressure (CPAP 6 cm H2O), and with oxygen (2 l/min via a mask) in random order on three separate days [43].
• We measured ambulatory 24-hour blood pressure (SpaceLab system), echocardiography (ASE criteria, Acuson 128 XP 10), CIn and CPAH, urinary Na excretion, PRA and insulin concentration [44].

References