Modulation of the H+/ATP coupling ratio by ADP and ATP as a possible regulatory feature in the F-type ATP synthases

Abstract

F-type ATP synthases are transmembrane enzymes, which play a central role in the metabolism of all aerobic and photosynthetic cells and organisms, being the major source of their ATP synthesis. Catalysis occurs via a rotary mechanism, in which the free energy of a transmembrane electrochemical ion gradient is converted into the free energy of ATP phosphorylation from ADP and Pi, and vice versa. An ADP, tightly bound to one of the three catalytic sites on the stator head, is associated with catalysis inhibition, which is relieved by the transmembrane proton gradient and by ATP. By preventing wasteful ATP hydrolysis in times of low osmotic energy and low ATP/ADP ratio, such inhibition constitutes a classical regulatory feedback effect, likely to be an integral component of in vivo regulation. The present miniview focuses on an additional putative regulatory phenomenon, which has drawn so far little attention, consisting in a substrate-induced tuning of the H+/ATP coupling ratio during catalysis, which might represent an additional key to energy homeostasis in the cell. Experimental pieces of evidence in support of such a phenomenon are reviewed.

F1·Fo ATP Synthase/ATPase: Contemporary View on Unidirectional Catalysis

“…To explain these data, the concept of two interconvertible states of ATP synthase, differing by their coupling ratios, was introduced. It has been suggested that the state with higher coupling ratios favors the binding of ADP, and the state with lower coupling ratios favors ATP binding [ 106 ].…”

Engineering of IF1‐susceptive bacterial F1‐ATPase

“…As previously reported (Hirono‐Hara et al, 2001 ; Kobayashi et al, 2020 , 2023 ), F 1 showed initial rapid ATP hydrolysis, followed by gradual deceleration to reach the steady‐state catalysis. This time‐dependent inactivation is due to the ADP inhibition, where F 1 molecules transiently lapse into an inactive state during catalysis (Figure S2 and Table S3 ; Lapashina & Feniouk, 2018 ; Turina, 2022 ). After confirming the steady‐state catalysis of F 1 , that is, 180 s after F 1 injection, IF 1 inhibition measurement was initiated by adding IF 1 into the reaction cuvette.…”

“…As previously reported (Hirono-Hara et al, 2001;Kobayashi et al, 2020Kobayashi et al, , 2023, F 1 showed initial rapid ATP hydrolysis, followed by gradual deceleration to reach the steady-state catalysis. This time-dependent inactivation is due to the ADP inhibition, where F 1 molecules transiently lapse into an inactive state during catalysis (Figure S2 and Table S3; Lapashina & Feniouk, 2018;Turina, 2022).…”