Protective metabolic mechanisms during liver ischemia: transferable lessons from long-diving animals.
During periods of O2 lack in liver of seals, mitochondrial respiration and adenosine triphosphate (ATP) synthesis are necessarily arrested. During such electron transfer system (ETS) arrest, the mitochondria are suspended in functionally protected states; upon resupplying O2 and adenosine diphosphate (ADP), coupled respiration and ATP synthesis can resume immediately, implying that mitochondrial electrochemical potentials required for ATP synthesis are preserved during ischemia. A similar situation occurs in the rest of the cell since ion gradients also seem to be maintained across the plasma membrane; with ion-specific channels seemingly relatively inactive, ion fluxes (e.g., K+ efflux and Ca++ influx) can be reduced, consequently reducing ATP expenditure for ion pumping. The need for making up energy shortfalls caused by ETS arrest is thus minimized, which is why anaerobic glycolysis can be held in low activity states (anaerobic ATP turnover rates being reduced in ischemia to less than 1/100 of typical normoxic rates in mammalian liver and to about 1/10 the rates expected during liver hypoperfusion in prolonged diving). As in many ectotherms, an interesting parallelism (channel arrest coupled with a proportionate metabolic arrest at the level of both glycolysis and the ETS) appears as the dominant hypoxia defense strategy in a hypoxia-tolerant mammalian organ.
Hochachka
P W
PW
Palmer Research Station, Palmer Peninsula, Antarctica.
Castellini
J M
JM
Hill
R D
RD
Schneider
R C
RC
Bengtson
J L
JL
Hill
S E
SE
Liggins
G C
GC
Zapol
W M
WM
D000818:Animals; D010872:Caniformia / Q000378:metabolism*; D004242:Diving / Q000009:adverse effects*; D006019:Glycolysis; D000860:Hypoxia / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D008930:Mitochondria, Liver / Q000378:metabolism; D010101:Oxygen Consumption; D011188:Potassium / Q000378:metabolism; D046048:Seals, Earless / Q000378:metabolism*
D011188:Potassium