Gnaiger 1998 Biochim Biophys Acta
|Gnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54.|
Abstract: Oxygen levels in the intracellular microenvironment of tissues such as heart are extremely low, at 1–2% of standard atmospheric oxygen pressure. Kinetic studies with isolated mitochondria suggest a regulatory role of oxygen under these conditions, particularly in active states at high ADP concentration, when oxygen affinity was lower than in the resting state at ADP limitation. The oxygen pressure at 50% of maximum flux, p50, was 0.035 and 0.057 kPa in heart and liver mitochondria, respiring in State 3 on substrates for Complex I or II and II, respectively. p50 in the resting State 4 was 0.02 kPa. The apparent kinetic efficiency, Jmax/p50, increased from the resting to the active state, despite the decrease of oxygen affinity, 1/p50. Consequently, the relative increase of respiratory flux by ADP activation, expressed as the respiratory acceptor control ratio, declined under hypoxia, but not to the extreme of a complete loss of the scope for activation, which would occur at constant Jmax/p50. High oxygen affinity is achieved by an excess capacity of cytochrome c oxidase relative to the Electron transfer-pathway and a correspondingly low turnover rate of this enzyme, consistent with the concept of kinetic trapping of oxygen .
• Keywords: Oxygen affinity, Catalytic efficiency, Respiratory control, Hypoxia, Mitochondrion, Heart, Liver
• O2k-Network Lab: AT Innsbruck Gnaiger E
Labels: MiParea: Respiration, Instruments;methods, Comparative MiP;environmental MiP
Organism: Rat Tissue;cell: Heart, Liver Preparation: Isolated mitochondria
Regulation: ADP, Flux control, Oxygen kinetics, Threshold;excess capacity, Uncoupler Coupling state: LEAK, OXPHOS, ET Pathway: N, S, CIV HRR: Oxygraph-2k
- State 2 in this publication has the meaning of a LEAK state of respiration, without added adenylates (no ADP and no ATP) in the presence of defined respiratory carbon substrates (different from the definition by Chance, Williams 1955).
- State 4 in this publication is a LEAK state of respiration induced by addition of defined respiratory carbon substrates and a high concenteration of ATP.
- State 3 is measured at high [ADP] close to saturated [ADP] (OXPHOS capacity) in the presence of added ATP.
- State 3u is induced by an optimum concentration of an uncoupler (FCCP) to obtain maximum oxygen flux ET-capacity.
Legend to Fig. 2: Instead of "pO2 was dependent ..." it should read: "p50 was dependent on respiratory rate, but also on metabolic state".