Newly Published
SPECIAL ARTICLE  |   February 2018
Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?
Author Notes
  • From Medical Service, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and the Department of Medicine and of Physiology and Biophysics, University of Washington, Seattle, Washington.
  • Figures were enhanced by Sara Jarret, C.M.I.
    Figures were enhanced by Sara Jarret, C.M.I.×
  • Submitted for publication April 16, 2017. Accepted for publication January 9, 2018.
    Submitted for publication April 16, 2017. Accepted for publication January 9, 2018.×
  • Research Support: Supported by the Department of Veterans Affairs, Seattle, Washington.
    Research Support: Supported by the Department of Veterans Affairs, Seattle, Washington.×
  • Competing Interests: The author declares no competing interests.
    Competing Interests: The author declares no competing interests.×
  • Correspondence: Address correspondence to Dr. Swenson: Pulmonary Section, S-111-Pulm Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Seattle, Washington 98108. swenson@u.washington.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Central and Peripheral Nervous Systems / Endocrine and Metabolic Systems / Renal and Urinary Systems / Electrolyte Balance
SPECIAL ARTICLE   |   February 2018
Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?
Anesthesiology Newly Published on February 14, 2018. doi:10.1097/ALN.0000000000002125
Anesthesiology Newly Published on February 14, 2018. doi:10.1097/ALN.0000000000002125
Abstract

Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long-abiding interest in acid–base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism. Dr. John Severinghaus has posited that hydrogen ion and bicarbonate are the direct end products in the Krebs cycle. In the late 1960s, he showed in brain and brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor, reduces intracellular pH. This led him to conclude that hydrogen ion and bicarbonate are the end products, and the role of intracellular carbonic anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis. Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs cycle, a more widely accepted view, and that acetazolamide prevents rapid intracellular bicarbonate formation, which can then codiffuse with carbon dioxide to the cell surface and there be reconverted for exit from the cell. Loss of this “facilitated diffusion of carbon dioxide” leads to intracellular acidosis as the still appreciable uncatalyzed rate of carbon dioxide hydration generates more protons. This review summarizes the available evidence and determines that resolution of this question will require more sophisticated measurements of intracellular pH with faster temporal resolution.