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Modulation Of The Cardiac Calcium Release Channel By Homocysteine Thiolactone, Laura Jean Owen

Dissertations and Theses

Elevated levels in blood serum (≥10μmol/L) of the amino acid homocysteine is strongly correlated with the incidence of heart failure (HF). We present evidence that the cyclic thioester, homocysteine thiolactone (HTL), a metabolic product of homocysteine, irreversibly modifies proteins that regulate the contractile process in cardiac muscle. Two proteins found in the sarcoplasmic reticulum (SR), the Ca²⁺ pump (SERCA2), and the ryanodine receptor (RyR2), are responsible for controlling the cytosolic Ca²⁺ concentration and hence the contractile state of the heart. While both improper Ca²⁺ handling and elevated homocysteine levels have been considered bio-markers in HF, a direct …