Use of a Rapid Assay of Subforms of Creatine Kinase MB to Diagnose or Rule Out Acute Myocardial Infarction

Puleo, Peter; Meyer, Denise; Wathen, C. H.; Tawa, C B; Wheeler, S.; Hamburg, Robert; Ali, Nina; Obermueller, Steve D.; Triana, J. F.; Zimmerman, Janice L.

doi:10.1056/nejm199409013310901

Cited by 297 publications

(91 citation statements)

References 36 publications

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“…Although CPU reduces plasminogen binding to both cells and in fibrin clots, the effect of CPN is largely restricted to removal of C-terminal Lys residues of plasma CPN also cleaves off C-terminal Lys residues from other large protein substrates; it is the "creatine kinase conversion factor" in blood that liberates the C-terminal Lys from both the M and B subunits of creatine kinase, released from the heart after myocardial infarction [84,85]. Determination of the ratio of the Lys-containing isoform to the des-Lys isoform increased the specificity and sensitivity of blood creatine kinase measurements for the diagnosis of heart attacks [86,87]. CPN can also remove Arg 141 from the α chain of human hemoglobin [88].…”

Section: Hydrolysis Of Biologically Relevant Peptides In Vivomentioning

confidence: 99%

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Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

Skidgel

Erdös

2007

International Immunopharmacology

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Human carboxypeptidase N (CPN) was discovered in the early 1960s as a plasma enzyme that inactivates bradykinin and was identified 8 years later as the major "anaphylatoxin inactivator" of blood. CPN plays in important role in protecting the body from excessive buildup of potentially deleterious peptides that normally act as local autocrine or paracrine hormones. This review summarizes the structure, enzymatic properties and function of this important human enzyme, including insights gained by the recent elucidation of the crystal structure of the CPN catalytic subunit and structural modeling of the non-catalytic regulatory 83 kDa subunit. We also discuss its physiological role in cleaving substrates such as kinins, anaphylatoxins, creatine kinase, plasminogen receptors, hemoglobin and stromal cell-derived factor-1α (SDF-1α). HistoryCarboxypeptidases were initially isolated from pancreatic extracts and so were associated with protein and peptide degradation in the digestive tract [1][2][3][4]. However, work beginning in the early 1960's by Erdös and Sloane [5] revealed the presence of a novel carboxypeptidase in the blood that plays a regulatory role by inactivating bradykinin via removal of its C-terminal Arg residue. (Subsequent research some 2 decades later led to the discovery of a second kinin B 1 receptor activated by the carboxypeptidase metabolite that is its endogenous agonist -see below). Initially it was assumed that the enzyme represents a circulating form of pancreatic carboxypeptidase B, but this was disproved by the characterization of its enzymatic properties [5][6][7][8], which was later borne out by biochemical studies, sequence analysis [9][10][11][12][13][14][15] and ultimately X-ray crystallography [16]. To differentiate it from the pancreatic enzyme, it was named carboxypeptidase N (CPN; EC 3.4.17.3) and was the first member of a family of carboxypeptidases now known as the regulatory or CPN/E subfamily of metallocarboxypeptidases [17][18][19]. It has since been re-discovered many times as other substrates were found and so has acquired aliases such as creatine kinase conversion factor, plasma carboxypeptidase B, arginine carboxypeptidase, lysine carboxypeptidase and protaminase [8,17,20,21]. The most notable was the finding by Bokisch and Müller-Eberhard in 1969 -70 [22,23] that the human plasma "anaphylatoxin inactivator" is identical with CPN. This finding explains our interest in the work of Dr. Tony Hugli, who has made many seminal contributions to the understanding of the structure and function of anaphylatoxins [24][25][26][27]. In Send Correspondence and Proofs To: Randal A. Skidgel, PhD, Dept. of Pharmacology (M/C 868), Univ. of Illinois College of Medicine, 835 S. Wolcott, Chicago, IL 60612, Phone: 312-996-9179, FAX: 312-996-1648, EMAIL: E-mail: rskidgel@uic.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript w...

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Section: Hydrolysis Of Biologically Relevant Peptides In Vivomentioning

confidence: 99%

“…Determination of the ratio of the Lys-containing isoform to the des-Lys isoform increased the specificity and sensitivity of blood creatine kinase measurements for the diagnosis of heart attacks [86,87]. CPN can also remove Arg 141 from the α chain of human hemoglobin [88].…”

Section: Hydrolysis Of Biologically Relevant Peptides In Vivomentioning

confidence: 99%

Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

Skidgel

Erdös

2007

International Immunopharmacology

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“…Use of the MBCK subforms was shown to diagnose myocardial infarction within 6 hours of onset of symptoms, and Ͼ60% of infarctions were detectable within the first hour of arriving in the emergency room (20 ). A prospective multicenter double-blind study, referred to as Diagnostic Marker Cooperative Study for the Diagnosis of Myocardial Infarction (21 ), was performed to compare myoglobin with the subforms for early diagnosis, and total MBCK, troponin I, and troponin T as markers for late diagnosis of infarction.…”

Section: Immunologic Detection Of Myocardial Infarctionmentioning

confidence: 99%

Cardiac Biomarkers for Detection of Myocardial Infarction: Perspectives from Past to Present

et al. 2004

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Editor’s Note: With great pleasure and anticipation in recognition of Clinical Chemistry’s 50th anniversary, I have been able to arm-twist four talented scientists to document their impressive marks on the science of diagnostics in the field of cardiac biomarkers and detection of myocardial infarction. Their exciting discoveries and applications have dramatically influenced the fields of laboratory medicine and cardiology and have greatly influenced the care and management of thousands of patients suffering from coronary artery disease leading to acute myocardial infarction. As a matter of historical record, I owe a great deal of thanks to each one of the coauthors of this special report because each one has personally influenced my scientific career. I met Dr. Rosalki, during my postdoctoral training, at a national AACC meeting, where he kindly answered my numerous queries regarding creatine kinase enzymology and muscle physiology. Dr. Roberts, while serving as Director of the Coronary Care Unit at Washington University in St. Louis, generously allowed this fledgling fellow into his laboratory and shared many of his clinical and experimental findings with me. Dr. Katus, whom I first met at a scientific meeting sponsored by Boehringer Mannheim in 1986 in Bavaria, where I first became fascinated with cardiac troponin T, has remained a friend and colleague. Lastly, Dr. Ladenson, who as mentor, scientific colleague, and close friend remains ultimately responsible for both my professional growth as a clinical chemist (he was my postdoctoral fellowship advisor) and for stimulating and encouraging my goals and aspirations in the field of cardiac biomarkers. With the descriptions of the ground-breaking science described below, I am extremely excited and optimistic that the future of cardiac biomarkers is secure and open to new discoveries by the Rosalkis, Robertses, Katuses, and Ladensons of the future. —Fred Apple

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“…10,11 Previous studies have documented ethnic difference in MPV level. [12][13][14][15] Association of higher MPV values with ACS has been mostly studied among Caucasian patients. 16 A few reports have revealed larger MPV values in Indian patient with ACS compared to healthy control.…”

Section: Introductionmentioning

confidence: 99%

Platelet volume indices in acute coronary syndrome - a case control study

2016

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Use of a Rapid Assay of Subforms of Creatine Kinase MB to Diagnose or Rule Out Acute Myocardial Infarction

Abstract: The assay of CK-MB subforms reliably detected myocardial infarction within the first six hours after the onset of symptoms, and its use could reduce admission to the coronary care unit by 50 to 70 percent, thereby reducing costs.

Cited by 297 publications

References 36 publications

Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

Cardiac Biomarkers for Detection of Myocardial Infarction: Perspectives from Past to Present

Platelet volume indices in acute coronary syndrome - a case control study

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