The sarcoplasmic reticulum Ca²⁺-ATPase, pumps 2 mol Ca²⁺ out of sarcomeres per mol ATP hydrolyzed. 

(a) Given the following steady-state concentrations and a membrane potential of 65 mV (inside negative), calculate ΔG for the following active transport process at 37 °C and pH = 7.4: 

(b) In active muscle the pH can drop below 7.4. Is the reaction above more or less favorable under these conditions? 

(c) The activity of the Ca²⁺-ATPase is regulated reversibly under normal conditions to maintain homeostatic concentrations of Ca²⁺ inside the sarcomere. However, in a rare genetic disorder, irreversible activation of the Ca²⁺-ATPase can occur. Assuming 37 °C, pH = 7.4, and the steady-state concentrations for ATP, ADP P_i , and Ca²⁺ _(out) given in part (a), calculate the minimum [Ca²⁺] inside a sarcomere that has irreversibly activated Ca²⁺-ATPase (i.e., the Ca²⁺-ATPase activity is always “on”).

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2Ca²+ (in) + ATP + H₂O→2Ca²+ + ADP + P₁ + H+ (out) ATP = 2.6 mM, ADP = 210 μM, P; = 5.1 mM, Ca²+, Ρ; = 2.2 mM Ca²+ (out) (in) = 32 μΜ,