Production of recombinant human creatine kinase (r-hCK) isozymes by tandem repeat expression of M and B genes and characterization of r-hCK-MB

Clin Chem. 2001 Mar;47(3):471-6.

Abstract

Background: Serum creatine kinase-MB isoenzyme (CK-MB) is widely used as a marker of myocardial injury. We prepared recombinant human CK (r-hCK) MB isoenzyme and examined its potential for use as a control material for assay of CK-MB in serum.

Methods: cDNAs encoding CK-M and CK-B subunits were inserted into the same plasmid vector, followed by transformation of Escherichia coli. The resulting three types of CK isoenzymes were purified by conventional chromatography.

Results: The ratio of MB to MM to BB was 50:40:10 on the basis of CK activity. Highly purified CK-MB with a specific activity of 533 U/mg was produced in a yield of 5.7 mg/g of packed cells. Purified r-hCK-MB had the isoelectric point (pI 5.3) and molecular size (46 kDa for the subunit) of native CK-MB. Its immunoreactivity in an ELISA using antibody against native heart enzyme was similar to that of cardiac CK-MB. The r-hCK-MB retained >90% activity for at least 4 months at 11 degrees C in a delipidated serum matrix in a liquid form at a concentration of 118 U/L.

Conclusions: r-hCK-MB shows key properties of the native cardiac isoenzyme and may be useful as a control and calibrator for serum assays of CK-MB.

MeSH terms

  • Creatine Kinase / biosynthesis*
  • Creatine Kinase / genetics
  • Creatine Kinase / isolation & purification
  • Creatine Kinase / standards
  • Creatine Kinase, BB Form
  • Creatine Kinase, MB Form
  • Creatine Kinase, MM Form
  • DNA, Complementary / genetics
  • DNA, Recombinant / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Humans
  • Immunoassay
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • Isoenzymes / isolation & purification
  • Isoenzymes / standards
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Reference Standards

Substances

  • DNA, Complementary
  • DNA, Recombinant
  • Isoenzymes
  • Recombinant Proteins
  • Creatine Kinase
  • Creatine Kinase, BB Form
  • Creatine Kinase, MB Form
  • Creatine Kinase, MM Form