Defining hypoxia: a systems view of VO2, glycolysis, energetics, and intracellular PO2

Connett, R. J.; Honig, Carl R.; Gayeski, T. E. J.; Brooks, George A.

doi:10.1152/jappl.1990.68.3.833

Cited by 358 publications

(232 citation statements)

References 52 publications

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“…The acid-base balance can be actively adjusted to enhance oxygen release at the respiring tissues. The oxygen affinities of enzyme complexes in metabolic pathways also contribute to oxygen flux (Connett et al, 1990). Gradients may also be influenced by substituting cellular constituents with different solubilities for oxygen and carbon dioxide.…”

Section: Kinetic and Physiological Control Of Organismal Metabolismmentioning

confidence: 99%

The real limits to marine life: a further critique of the Respiration Index

Seibel

Childress

2013

Biogeosciences

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The recently proposed "Respiration Index" (RI = log PO₂/PCO₂) suggests that aerobic metabolism is limited by the ratio of reactants (oxygen) to products (carbon dioxide) according to the thermodynamics of cellular respiration. Here, we demonstrate further that, because of the large standard free energy change for organic carbon oxidation (ΔG° = −686 kcal mol⁻¹), carbon dioxide can never reach concentrations that would limit the thermodynamics of this reaction. A PCO₂ to PO₂ ratio of 10⁵⁰³ would be required to reach equilibrium (equilibrium constant, K_eq = 10⁵⁰³), where ΔG = 0. Thus, a Respiration Index of −503 would be the real thermodynamic limit to aerobic life. Such a Respiration Index is never reached, either in the cell or in the environment. Moreover, cellular respiration and oxygen provision are kinetically controlled such that, within limits, environmental oxygen and CO₂ concentrations have little to do with intracellular concentrations. The RI is fundamentally different from the aragonite saturation state, a thermodynamic index used to quantify the potential effect of CO₂ on calcification rates, because of its failure to incorporate the equilibrium constant of the reaction. Not only is the RI invalid, but its use leads to incorrect and misleading predictions of the threat of changing oxygen and carbon dioxide to marine life. We provide a physiological framework that identifies oxygen thresholds and allows for synergistic effects of ocean acidification and global warming

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Section: Kinetic and Physiological Control Of Organismal Metabolismmentioning

confidence: 99%

The real limits to marine life: a further critique of the Respiration Index

Seibel

Childress

2013

Biogeosciences

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“…Al though the observed reduction in astrocyte ATP levels during chemical hypoxia supports this mech anism, the relationship between cellular ATP levels and glutamate transport may be complex. As noted by Connett et al (1990), compensatory mechanisms may reduce A TP utilization and net A TP flux during hypoxia, and reductions in ATP levels may there fore underestimate the degree of energy failure. The dominant mechanism of glutamate uptake under normal conditions is sodium dependent (Cho and Bannai, 1990;Balcar and Yi, 1992).…”

Section: Media Phmentioning

confidence: 99%

Acidosis Causes Failure of Astrocyte Glutamate Uptake during Hypoxia

Swanson

Farrell

Simon

1995

J Cereb Blood Flow Metab

136

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Summary: Failure of glutamate uptake during ischemia can lead to neurotoxic accumulations of glutamate in brain extracellular space. Hypoxia and acidosis are met abolic consequences of ischemia that may individually or in combination impair glutamate uptake. We used pri mary rat astrocyte cultures to study the effects of acido sis, chemical hypoxia, and the combination of acidosis plus chemical hypoxia on glutamate uptake. Chemical hypoxia alone reduced uptake by 35-45%. Reduction in pH from 7.4 to 5.8 also caused a significant but incom plete inhibition of glutamate uptake, and this effect was more pronounced in medium buffered with CO2/ bicarbonate. However, the combination of chemical hyp oxia plus acidosis reduced glutamate uptake to below Focal cerebral ischemia can cause marked reduc tions in tissue pH as a result of continued glycolytic metabolism and lactic acid production. As recently reviewed by Siesj6 et al. (1993) and Tombaugh and Sapolsky (1993), acidosis has complex effects on ischemic brain injury. Acidosis can reduce Ca2 + flux through N-methyl-D-aspartate (NMDA) recep tor-gated channels and decrease excitotoxic death in cultured neurons. However, acidosis is also re ported to increase Ca2 + influx in hypoxic brain slice preparations (O'Donnell and Bickler, 1994) and to have varying effects on ischemic injury in vivo (My ers and Yamaguchi, 1977; Simon et aI., 1993; Kat sura et aI., 1994). The present study addresses a further effect of acidosis that may largely account for these apparently conflicting results: impairment 41710% of controls. Astrocyte ATP levels, like glutamate uptake, were significantly reduced by chemical hypoxia and further reduced by the combination of hypoxia plus acidosis. Acidosis'under normoxic conditions had no sig nificant effect on astrocyte ATP levels. These results sug gest two mechanisms by which acidosis may contribute to failure of astrocyte glutamate uptake during ischemia: Acidosis may act in concert with hypoxia to cause A TP depletion, and acidosis may also have direct effects on glutamate transporters unrelated to effects on cellular ATP levels. pH effects on glutamate uptake may be an important factor affecting neuronal survival during in complete ischemia.

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“…Even the energy-efficient anaerobic metabolic pathways resulting in the accumulation of succinate and propionate are well below the efficiency of aerobic metabolism (Seibel 2011). Therefore, activation of anaerobic metabolism pathways requires large stores of fermentable substrates, and depletion of energy reserves during sustained hypoxia or anoxia eventually results in impaired function or death (Connett et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Biochemical responses to anoxia and hypoxia in the ark shell Scapharca kagoshimensis

Miyamoto

Iwanaga

2012

Plankton Benthos Res

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Metabolic adaptation to 7-d sustained anoxia, and the activation of anaerobic metabolism by a series of O 2 concentrations during a 12-h period, were examined in the ark shell Scapharca kagoshimensis. Laboratory experiments and biochemical analyses were conducted under summer conditions. The pattern of metabolic adaptation to prolonged anoxia was clearly biphasic, similar to that in many other bivalve species. The first, transition stage lasted 12 h and was characterized by sharp decreases in adenylate energy charge, aspartate consumption, and accumulation of succinate and alanine. The second, stationary stage was characterized by glycogen depletion and propionate accumulation. In a series of dissolved oxygen (DO) conditions, the onset of anaerobic metabolism (as indicated by a decrease in fermentative substrate, aspartate; and increase in the end-products, succinate and alanine) was detected only under hypoxic conditions (< 2 mg O 2 L 1 ) and was accompanied by depressed physiological performance, as measured by clearance rate and ammonium excretion rate. However, under milder hypoxia (1-2 mg O 2 L 1 ), a significant clearance rate was still observed, suggesting that both aerobic and anaerobic metabolisms were contributing toward the ATP yield. Lower DO (< 0.61 mg O 2 L 1 ) resulted in an increased rate of anaerobic metabolism and inactivated aerobic ATP production due to impaired filter feeding.

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Defining hypoxia: a systems view of VO2, glycolysis, energetics, and intracellular PO2

Cited by 358 publications

References 52 publications

The real limits to marine life: a further critique of the Respiration Index

The real limits to marine life: a further critique of the Respiration Index

Acidosis Causes Failure of Astrocyte Glutamate Uptake during Hypoxia

Biochemical responses to anoxia and hypoxia in the ark shell Scapharca kagoshimensis

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