Nature and time course of generation of creatine kinase, MB fraction in vivo

Nelson A. Prager, Tadao Suzuki, Allan S Jaffe, Burton E. Sobel, Dana R. Abendschein

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objectives. This study was designed to characterize the nature and time course of carboxy-terminal lysine cleavages from the tissue isoform of MB creatine kinase (CK) in vivo. Background. Rapid conversion of the tissue isoform of MM CK to two additional circulating isoforms with one or both carboxyterminal lysines cleaved facilitates early detection of new tissue isoform release after acute myocardial infarction and coronary recanalization. Characterization of changes in plasma MB CK isoform profiles, potentially enhancing specificity even further, has been hindered by difficulties in separating the isoform products and elucidation of carboxy-terminal lysine cleavages underlying their formation. Methods. Isoform species with carboxy-terminal lysine present on B-monomers were separated from those from which lysine had been cleaved by anion exchange chromatography. Carboxyterminal lysine on M-monomers was assayed with the use of a monospecific antibody. Results. MB CK in four pooled plasma samples from among 77 normal subjects exhibited carboxy-terminal lysine on 48 ± 21% (mean ± SEM) of B-monomers and 82 ± 12% of M-monomers. Within the 1st 16 h alter the onset of acute myocardial infarction, virtually all M- and B-monomers exhibited carboxy-terminal lysine, indicating release into plasma and the lack of rapid cleavage of lysine from the tissue isoform. After 20 to 30 h, 43 ± 9% (three pools from 19 patients) of B-monomers and 95 ± 10% of M-monomers exhibited lysine at the carboxyl terminus. After 40 to 50 h, 13 ± 13% (four pools from 34 patients) of B-monomers and 46 ± 19% of M-monomers still retained carboxy-terminal lysine. Conclusions. In contrast to MM CK, the tissue isoform of MB CK undergoes slow cleavage of lysine from both monomers in vivo. Sequential cleavage of lysine first from the carboxyl terminus of B-monomers and subsequently from M-monomers is consistent with generation of at least two additional isoforms. Development of assays capable of resolving all of the isoforms of MB CK that can occur in vivo might increase sensitivity for early detection of new tissue isoform release associated with acute myocardial infarction and coronary recanalization compared with currently available assays that resolve only two species.

Original languageEnglish (US)
Pages (from-to)414-419
Number of pages6
JournalJournal of the American College of Cardiology
Volume20
Issue number2
DOIs
StatePublished - 1992
Externally publishedYes

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MB Form Creatine Kinase
Lysine
Protein Isoforms
MM Form Creatine Kinase
Myocardial Infarction
Anions
Chromatography

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Nature and time course of generation of creatine kinase, MB fraction in vivo. / Prager, Nelson A.; Suzuki, Tadao; Jaffe, Allan S; Sobel, Burton E.; Abendschein, Dana R.

In: Journal of the American College of Cardiology, Vol. 20, No. 2, 1992, p. 414-419.

Research output: Contribution to journalArticle

Prager, Nelson A. ; Suzuki, Tadao ; Jaffe, Allan S ; Sobel, Burton E. ; Abendschein, Dana R. / Nature and time course of generation of creatine kinase, MB fraction in vivo. In: Journal of the American College of Cardiology. 1992 ; Vol. 20, No. 2. pp. 414-419.
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abstract = "Objectives. This study was designed to characterize the nature and time course of carboxy-terminal lysine cleavages from the tissue isoform of MB creatine kinase (CK) in vivo. Background. Rapid conversion of the tissue isoform of MM CK to two additional circulating isoforms with one or both carboxyterminal lysines cleaved facilitates early detection of new tissue isoform release after acute myocardial infarction and coronary recanalization. Characterization of changes in plasma MB CK isoform profiles, potentially enhancing specificity even further, has been hindered by difficulties in separating the isoform products and elucidation of carboxy-terminal lysine cleavages underlying their formation. Methods. Isoform species with carboxy-terminal lysine present on B-monomers were separated from those from which lysine had been cleaved by anion exchange chromatography. Carboxyterminal lysine on M-monomers was assayed with the use of a monospecific antibody. Results. MB CK in four pooled plasma samples from among 77 normal subjects exhibited carboxy-terminal lysine on 48 ± 21{\%} (mean ± SEM) of B-monomers and 82 ± 12{\%} of M-monomers. Within the 1st 16 h alter the onset of acute myocardial infarction, virtually all M- and B-monomers exhibited carboxy-terminal lysine, indicating release into plasma and the lack of rapid cleavage of lysine from the tissue isoform. After 20 to 30 h, 43 ± 9{\%} (three pools from 19 patients) of B-monomers and 95 ± 10{\%} of M-monomers exhibited lysine at the carboxyl terminus. After 40 to 50 h, 13 ± 13{\%} (four pools from 34 patients) of B-monomers and 46 ± 19{\%} of M-monomers still retained carboxy-terminal lysine. Conclusions. In contrast to MM CK, the tissue isoform of MB CK undergoes slow cleavage of lysine from both monomers in vivo. Sequential cleavage of lysine first from the carboxyl terminus of B-monomers and subsequently from M-monomers is consistent with generation of at least two additional isoforms. Development of assays capable of resolving all of the isoforms of MB CK that can occur in vivo might increase sensitivity for early detection of new tissue isoform release associated with acute myocardial infarction and coronary recanalization compared with currently available assays that resolve only two species.",
author = "Prager, {Nelson A.} and Tadao Suzuki and Jaffe, {Allan S} and Sobel, {Burton E.} and Abendschein, {Dana R.}",
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T1 - Nature and time course of generation of creatine kinase, MB fraction in vivo

AU - Prager, Nelson A.

AU - Suzuki, Tadao

AU - Jaffe, Allan S

AU - Sobel, Burton E.

AU - Abendschein, Dana R.

PY - 1992

Y1 - 1992

N2 - Objectives. This study was designed to characterize the nature and time course of carboxy-terminal lysine cleavages from the tissue isoform of MB creatine kinase (CK) in vivo. Background. Rapid conversion of the tissue isoform of MM CK to two additional circulating isoforms with one or both carboxyterminal lysines cleaved facilitates early detection of new tissue isoform release after acute myocardial infarction and coronary recanalization. Characterization of changes in plasma MB CK isoform profiles, potentially enhancing specificity even further, has been hindered by difficulties in separating the isoform products and elucidation of carboxy-terminal lysine cleavages underlying their formation. Methods. Isoform species with carboxy-terminal lysine present on B-monomers were separated from those from which lysine had been cleaved by anion exchange chromatography. Carboxyterminal lysine on M-monomers was assayed with the use of a monospecific antibody. Results. MB CK in four pooled plasma samples from among 77 normal subjects exhibited carboxy-terminal lysine on 48 ± 21% (mean ± SEM) of B-monomers and 82 ± 12% of M-monomers. Within the 1st 16 h alter the onset of acute myocardial infarction, virtually all M- and B-monomers exhibited carboxy-terminal lysine, indicating release into plasma and the lack of rapid cleavage of lysine from the tissue isoform. After 20 to 30 h, 43 ± 9% (three pools from 19 patients) of B-monomers and 95 ± 10% of M-monomers exhibited lysine at the carboxyl terminus. After 40 to 50 h, 13 ± 13% (four pools from 34 patients) of B-monomers and 46 ± 19% of M-monomers still retained carboxy-terminal lysine. Conclusions. In contrast to MM CK, the tissue isoform of MB CK undergoes slow cleavage of lysine from both monomers in vivo. Sequential cleavage of lysine first from the carboxyl terminus of B-monomers and subsequently from M-monomers is consistent with generation of at least two additional isoforms. Development of assays capable of resolving all of the isoforms of MB CK that can occur in vivo might increase sensitivity for early detection of new tissue isoform release associated with acute myocardial infarction and coronary recanalization compared with currently available assays that resolve only two species.

AB - Objectives. This study was designed to characterize the nature and time course of carboxy-terminal lysine cleavages from the tissue isoform of MB creatine kinase (CK) in vivo. Background. Rapid conversion of the tissue isoform of MM CK to two additional circulating isoforms with one or both carboxyterminal lysines cleaved facilitates early detection of new tissue isoform release after acute myocardial infarction and coronary recanalization. Characterization of changes in plasma MB CK isoform profiles, potentially enhancing specificity even further, has been hindered by difficulties in separating the isoform products and elucidation of carboxy-terminal lysine cleavages underlying their formation. Methods. Isoform species with carboxy-terminal lysine present on B-monomers were separated from those from which lysine had been cleaved by anion exchange chromatography. Carboxyterminal lysine on M-monomers was assayed with the use of a monospecific antibody. Results. MB CK in four pooled plasma samples from among 77 normal subjects exhibited carboxy-terminal lysine on 48 ± 21% (mean ± SEM) of B-monomers and 82 ± 12% of M-monomers. Within the 1st 16 h alter the onset of acute myocardial infarction, virtually all M- and B-monomers exhibited carboxy-terminal lysine, indicating release into plasma and the lack of rapid cleavage of lysine from the tissue isoform. After 20 to 30 h, 43 ± 9% (three pools from 19 patients) of B-monomers and 95 ± 10% of M-monomers exhibited lysine at the carboxyl terminus. After 40 to 50 h, 13 ± 13% (four pools from 34 patients) of B-monomers and 46 ± 19% of M-monomers still retained carboxy-terminal lysine. Conclusions. In contrast to MM CK, the tissue isoform of MB CK undergoes slow cleavage of lysine from both monomers in vivo. Sequential cleavage of lysine first from the carboxyl terminus of B-monomers and subsequently from M-monomers is consistent with generation of at least two additional isoforms. Development of assays capable of resolving all of the isoforms of MB CK that can occur in vivo might increase sensitivity for early detection of new tissue isoform release associated with acute myocardial infarction and coronary recanalization compared with currently available assays that resolve only two species.

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