Regulation of the Oxidative Phosphorylation Rate in the Intact Cell

Arthur H From, Stevan D. Zimmer, Steve P. Michurski, Parakket Mohanakrishnan, Valerie K. Ulstad, William J. Thoma, Kamil Ugurbil

Research output: Contribution to journalArticle

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Abstract

The mechanisms that underlie the balance between the consumption and oxidative generation of ATP in the intact cell are not well-defined. Cytosolic inorganic phosphate (Pi) and ADP levels, the cytosolic ATP/ADP ratio, and the cytosolic phosphorylation potential (PP) have all been proposed as major regulatory variables, the latter as a component of a “near-equilibrium” thermodynamic regulatory scheme. Therefore, the potential regulatory roles of these variables in the intact cell were evaluated with 31P NMR and Langendorff perfused rat hearts; in this preparation, the tissue oxygen consumption rate (MV02) can be varied over a wide range. When the exogenous carbon source was varied, none of the proposed regulatory parameters, i.e., the ATP/ADP ratio, PP, or cytosolic ADP level, were found to be uniquely related to MV02. Rather, ADP levels at a given MV02 decreased progressively for the exogenous carbon sources in the following order: glucose, glucose + insulin, palmitate + glucose, lactate, pyruvate + glucose, and octanoate + glucose. In the octanoate and pyruvate groups, MV02 _1 was linearly dependent upon [ADP]−1 with apparent Km values being in the range previously observed in isolated mitochondria. A similar trend was observed in the MV02-[Pi] relationship. The present findings suggest that exogenous carbon sources which effectuate deregulation of intramitochondrial NADH generation lower cytosolic ADP and Pi to levels which are limiting to the rate of oxidative phosphorylation. For other carbon sources, the processes controlling the rate of NADH generation also participate in determining the rate of oxidative ATP synthesis. However, this control must be exerted kinetically rather than through a near-equilibrium thermodynamic mechanism as indicated by the present data and prior kinetic studies of the ATP synthetic process in both isolated mitochondria and intact myocardium [La Noue, K. F., et al. (1986) Biochemistry 25, 7667–7675; Kingsley-Hickman, P., et al. (1987) Biochemistry 26, 7501–7510].

Original languageEnglish (US)
Pages (from-to)3731-3743
Number of pages13
JournalBiochemistry
Volume29
Issue number15
DOIs
StatePublished - Apr 1 1990

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Oxidative Phosphorylation
Adenosine Diphosphate
Adenosine Triphosphate
Glucose
Carbon
Biochemistry
Phosphorylation
Mitochondria
Pyruvic Acid
Thermodynamics
NAD
Deregulation
Palmitates
Oxygen Consumption
Rats
Lactic Acid
Myocardium
Phosphates
Nuclear magnetic resonance
Insulin

Cite this

From, A. H., Zimmer, S. D., Michurski, S. P., Mohanakrishnan, P., Ulstad, V. K., Thoma, W. J., & Ugurbil, K. (1990). Regulation of the Oxidative Phosphorylation Rate in the Intact Cell. Biochemistry, 29(15), 3731-3743. https://doi.org/10.1021/bi00467a020

Regulation of the Oxidative Phosphorylation Rate in the Intact Cell. / From, Arthur H; Zimmer, Stevan D.; Michurski, Steve P.; Mohanakrishnan, Parakket; Ulstad, Valerie K.; Thoma, William J.; Ugurbil, Kamil.

In: Biochemistry, Vol. 29, No. 15, 01.04.1990, p. 3731-3743.

Research output: Contribution to journalArticle

From, AH, Zimmer, SD, Michurski, SP, Mohanakrishnan, P, Ulstad, VK, Thoma, WJ & Ugurbil, K 1990, 'Regulation of the Oxidative Phosphorylation Rate in the Intact Cell', Biochemistry, vol. 29, no. 15, pp. 3731-3743. https://doi.org/10.1021/bi00467a020
From AH, Zimmer SD, Michurski SP, Mohanakrishnan P, Ulstad VK, Thoma WJ et al. Regulation of the Oxidative Phosphorylation Rate in the Intact Cell. Biochemistry. 1990 Apr 1;29(15):3731-3743. https://doi.org/10.1021/bi00467a020
From, Arthur H ; Zimmer, Stevan D. ; Michurski, Steve P. ; Mohanakrishnan, Parakket ; Ulstad, Valerie K. ; Thoma, William J. ; Ugurbil, Kamil. / Regulation of the Oxidative Phosphorylation Rate in the Intact Cell. In: Biochemistry. 1990 ; Vol. 29, No. 15. pp. 3731-3743.
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