Metabolic meaning of elevated levels of oxidative enzymes in high altitude adapted animals: An interpretive hypothesis

Abstract

It is commonly observed that during acclimatization to altitude oxidative enzyme activities increase per g wet weight of tissue. To examine this problem in long-term adapted animals we measured citrate synthase (CS), hydroxyacylCoA dehydrogenase (HOAD), pyruvate kinase (PK), and lactate dehydrogenase (LDH) activities/g of myocardium in two domestic species (llama and alpaca) and a high altitude deer, the taruca. In all these species, we found an upward scaling of oxidative capacity (indicated by absolute activities of CS and HOAD) but a downward scaling of anaerobic/aerobic metabolic potentials of the heart (indicated by low ratios of LDH/CS, and LDH/HOAD, but high ratios of PK/LDH). As the direction and magnitude of these long-term adaptations are the same as in shorter-term acclimizations, we wondered why a similar pattern at the enzyme level correlates with the right shift of the O 2 dissociation curve (ODC) in the latter case, but with a left shifted ODC in the former. We hypothesize that in the long term, increased oxidative enzyme activities allow increased maximum flux capacity of aerobic metabolism. This in turn call for physiological adjustments in O 2 transfer systems; flux limits of the former must be matched by flux limits of the latter. Only then can an acceptably high scope for aerobic activity be achieved despite reduced O 2 availability in inspired air. Such long-term match-up invariably calls for a left-shifted ODC plus other well known adjustments in O 2 transport. In the short term, right shifting the ODC may increase the total amount of aerobic work possible (by favoring O 2 unloading and thus raising tissue O 2 concentration), yet maximum flux capacity cannot be changed much because mitochondrial metabolism is designed for maintaining stable rates of ATP synthesis even at widely varying O 2 tensions. That is why even in short-term acclimization, in order to increase flux capacity, the activities of oxidative enzymes also must be increased.