Kinetic analysis of impaired work-cost performance in jaundiced rabbit liver

Impairment of energy metabolism was studied in jaundiced rabbit liver by kinetic analysis of energy transfer function. Free cytosolic ADP (ADP_f), as calculated from the measured components of the glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase/lactate dehydrogenase reactions, decreased from the control value of 48.1 to 37.0 μM at 24 h after bile duct ligation. The maximal velocity (V_max) of ATP synthesis, as measured by state 3 respiration of isolated mitochondria, decreased from the control value of 62.1 to 38.3 nmol ATP synthesized per min per mg mitochondrial protein, while the Michaelis constant for ADP (K _m) decreased from the control value of 19.2 to 12.8 μM. ATP synthesis velocity in vivo {v:V_max/[1+(K _m/[ADP_f])]}, as calculated by V_max,K _m and ADP_f, decreased from the control value of 44.4 to 28.5 nmol ATP synthesized per min per mg mitochondrial protein. Δv/ΔADP_f (Δv/ΔADP_f: V_max·K _m/(K _m+[ADP_f])²), which indicates work-cost performance of the liver, decreased from the control value of 0.263 to 0.198. Biochemical output of the liver, as measured by hippurate synthesis from benzoate, decreased from the control value of 98.4 to 32.7 mg/h. These results indicate that synergistic decreases in ADP_f, V_max, v and Δv/ΔADP_f take place in the course of deterioration of mitochondrial ATP synthesis and work output in jaundiced liver