Conversion of MM creatine kinase isoforms in human plasma by carboxypeptidase N.
This study was undertaken to identify the carboxypeptidase(s) (CPase) in plasma mediating sequential conversion of the tissue isoform of the MM isoenzyme of creatine kinase (MM3 CK) to MM2 and MM1 isoforms and to elucidate relationships between CPase activity measured in plasma and observed rates of isoform conversion in vitro. Purified MM3 was incubated at 37 degrees C in plasma from normal subjects and patients with acute myocardial infarction. Isoforms were quantified by chromatofocusing. Preincubation with antiserum to CPase N prevented conversion of added MM3 to MM2 and MM1. Isoform conversion rates in the absence of antibody were proportional to plasma CPase N activity assayed spectrophotometrically by hydrolysis of furylacryloyl-L-alanyl-L-lysine substrate (r = 0.89, n = 8). Plasma CPase N activity varied by nearly 300% among individuals, but average activity was similar in samples from normal subjects (267 +/- 45 [SD] U/L, n = 18), those from outpatients with angina (289 +/- 43 U/L, n = 9), and those obtained at hospital admission from patients with acute infarction (Q wave: 279 +/- 70 U/L, n = 16; non-Q wave: 272 +/- 61 U/L, n = 14) or unstable angina (280 +/- 71 U/L, n = 11). In patients with Q wave infarction, CPase N activity increased by 43% +/- 25% between 48 hours and 72 hours (P less than 0.005 compared with admission) with a concomitant change in the rate of conversion of isoforms. Thus, the rate of conversion of isoforms in individual subjects can be estimated by assay of CPase N activity in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Abendschein
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DR
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
Serota
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Plummer
T H
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Amiraian
K
K
Strauss
A W
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Sobel
B E
BE
Jaffe
A S
AS
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000097:blood*; D043422:Carboxypeptidases A; D003327:Coronary Disease / Q000201:enzymology; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006801:Humans; D007527:Isoenzymes; D001121:Lysine Carboxypeptidase / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013386:Succinates / Q000494:pharmacology
D007527:Isoenzymes; D013386:Succinates; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; C022014:guanidinoethylmercaptosuccinic acid; C000249:benzylsuccinic acid; D015097:3-Mercaptopropionic Acid; D003402:Creatine Kinase; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D001121:Lysine Carboxypeptidase