Date of Award
Open Access Thesis
Medical Doctor (MD)
Paul K Maciejewski
For decades the oxidative efficiency of cellular metabolism has been under investigation. After numerous reports of varied stoichiometric measurements, consensus in the literature has begun moving toward two currently accepted theoretical P/O ratios (the number of adenosine triphosphate (ATP) molecules formed for every oxygen atom consumed): 2.5 for NADH-linked substrates and 1.5 for FADH2-linked substrates. It is shown here, however, that the currently accepted theoretical values are inappropriately calculated underestimates, and that P/O ratios of real biochemical systems are variable. The complete oxidative metabolism of glucose, beta-hydroxybutyrate, malate, pyruvate, and succinate, utilizing three different electron shuttles (or exclusive mitochondrial metabolism) and two different values of the H+/ATP ratio (4 and 13/3) is examined using a new method of analysis. Calculations are made within the rigid mathematical framework of linear algebra, relying on the Law of Conservation of Matter as a first principle. Calculated P/O values from systems modeled after cell-free mitochondrial extracts ranged from 2.711 to 3.183, or 3.000 to 3.500 depending on H+/ATP ratios of 13/3 or 4/1, respectively. These estimates are within the range of measured values (1.07 - 3.73) but are higher than the commonly accepted theoretical values of ~2.5 and ~1.5 for NADH and FADH2-linked substrates, respectively. A new view of the P/O ratio as variable, based on specific details of molecular physiology, is offered as a potentially useful means for understanding variation in measured values of the P/O ratio reported in the literature.
Walled, Douglas, "Cellular Oxidative Efficiency: A New Approach to Calculating Theoretical P/O Ratios" (2006). Yale Medicine Thesis Digital Library. 302.