SH1 thiols are essential to the increased actin-activated ATPase activity of cardiac myosin in thyrotoxicosis, suggesting thyroxine-induced enzymatic changes alter heart contractile properties.
The Ca2+-ATPase activity of cardiac myosin is increased in thyrotoxic animals. However, the physiological significance of this observation is uncertain since, in living muscle, Mg-ATP is hydrolyzed by myosin under the stimulating influence of actin. In this study, we have compared the actin-activated ATPase activity of myosin from euthyroid (myosin-N) and thyrotoxic (myosin-T) rabbits and the derivatives of myosin-N and myosin-T formed by blocking the most rapidly reacting class of thiols (SH1) with N-ethylmaleimide (NEM). Also, we have studied the activity of these myosins in the presence of a complex of troponin and tropomyosin that confers calcium sensitivity on the system. Vmax for the actin-activated ATPase of myosin-T was about 168% greater than for myosin N. The apparent dissociation constant for actin, Kapp, for myosin-T was about 42% of the normal value. After NEM modification, Vmax and Kapp for NEM-modified myosin-T and myosin-N decreased, becoming essentially the same for both myosins. In the presence of troponin-tropomyosin complex, the actin-activated ATPase of myosin-T exhibited calcium sensitivity that could be reduced by thiol modification. These results suggest that the SH1 thiols or the region near these groups are important to the actin-activated ATPase of myosin-N and are essential to the increased activity of myosin-T. Also, they suggest that the changes in the enzymatic properties of myosin induced by thyroxine may be responsible for altering the contractile properties of the heart.
Banerjee et al. (Tue,) studied this question.