Troponin T and Troponin I are released from cardiomyocytes after myocardial injury. Unlike creatine kinase-MB, cardiac troponins have almost no false-positive elevation from skeletal muscle disease. What biochemical property of cardiac isoforms accounts for their cardiac specificity?

• A Cardiac troponins are larger proteins that cannot cross the sarcolemma of normal skeletal muscle cells
• B Skeletal muscle lacks troponin proteins entirely, making any serum troponin cardiac-specific
• C Cardiac troponin T (cTnT) and I (cTnI) isoforms are encoded by cardiac-specific genes with unique epitopes absent from skeletal muscle isoforms ✓
• D Cardiac troponins are glycoproteins while skeletal isoforms are non-glycosylated, allowing specific antibody discrimination

Explanation

Cardiac troponin T and troponin I are encoded by separate cardiac-specific genes (TNNT2 and TNNI3) producing isoforms with distinct amino acid sequences, particularly at the N-terminal regions. Modern high-sensitivity troponin assays use monoclonal antibodies targeting epitopes unique to these cardiac isoforms that are absent from skeletal muscle troponins. This cardiac-specific protein structure provides the organ specificity. In contrast, CK-MB is expressed in both cardiac and regenerating/diseased skeletal muscle, reducing its specificity. cTnI is more cardiac-specific than cTnT, as cTnT can be expressed in regenerating skeletal muscle in some conditions.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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