Abstract
This paper considers the way in which the oxygen reaction described by Dr. Nicholls and the ADP control reactions described by Dr. Racker could cooperate to establish a purposeful metabolic control phenomenon in vivo. This has required an examination of the kinetic properties of the respiratory chain with particular reference to methods for determinations of oxygen affinity (Km). The constant parameter for tissue respiration is k 1, the velocity constant for the reaction of oxygen with cytochrome oxidase. Not only is this quantity a constant for a particular tissue or mitochondria; it appears to vary little over a wide range of biological material, and for practical purposes a value of 5 x 107 at 25° close to our original value (20) is found to apply with adequate accuracy for calculation of Km for mammalia. The quantity which will depend upon the tissue and its metabolic state is the value of Km itself, and Km may be as large as 0.5 µM and may fall to 0.05 µM or less in resting, controlled, or inhibited states. The control characteristic for ADP may depend upon the electron flux due to the cytochrome chain (40); less ADP is required to activate the slower electron transport at lower temperatures than at higher temperatures. The affinity constants for ADP control appear to be less dependent upon substrate supplied to the system. The balance of ADP and oxygen control in vivo is amply demonstrated experimentally and is dependent on the oxygen concentration as follows. In the presence of excess oxygen, control may be due to the ADP or phosphate (or substrate), and the kinetics of oxygen utilization will be independent of the oxygen concentration. As the oxygen concentration is diminished, hemoglobin becomes disoxygenated, deep gradients of oxygen concentration develop in the tissue, and eventually cytochrome oxidase becomes partially and then completely reduced. DPN at this point will become reduced and the electron flow diminished. The rate of ATP production falls and energy conservation previously under the control of the ADP concentration will now be controlled by the diffusion of oxygen to the respiratory enzymes in the mitochondria. Under these conditions the rate of reaction of cytochrome oxidase with oxygen and the reaction of cytochromes with one another become of key importance. The rise of ADP and the depletion of energy reserves evoke glycolytic activity, and failure of biological function may result.
Full Text
The Full Text of this article is available as a PDF (1.4 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Butow R. A., Racker E. On the mechanism of respiratory control. J Gen Physiol. 1965 Sep;49(1 Suppl):149–162. doi: 10.1085/jgp.49.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHANCE B., CONNELLY C. M. A method for the estimation of the increase in concentration of adenosine diphosphate in muscle sarcosomes following a contraction. Nature. 1957 Jun 15;179(4572):1235–1237. doi: 10.1038/1791235a0. [DOI] [PubMed] [Google Scholar]
- CHANCE B. Cellular oxygen requirements. Fed Proc. 1957 Sep;16(3):671–680. [PubMed] [Google Scholar]
- CHANCE B. Kinetics of enzyme reactions within single cells. Ann N Y Acad Sci. 1962 Jun 5;97:431–448. doi: 10.1111/j.1749-6632.1962.tb34655.x. [DOI] [PubMed] [Google Scholar]
- CHANCE B., PACKER L. Light-scattering and absorption effects caused by addition of adenosine diphosphate to rat-heart-muscle sarcosomes. Biochem J. 1958 Feb;68(2):295–297. doi: 10.1042/bj0680295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHANCE B., PARSONS D. F., WILLIAMS G. R. CYTOCHROME CONTENT OF MITOCHONDRIA STRIPPED OF INNER MEMBRANE STRUCTURE. Science. 1964 Jan 10;143(3602):136–139. doi: 10.1126/science.143.3602.136. [DOI] [PubMed] [Google Scholar]
- CHANCE B., WILLIAMS G. R. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem. 1955 Nov;217(1):383–393. [PubMed] [Google Scholar]
- CHANCE B., WILLIAMS G. R. Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem. 1955 Nov;217(1):409–427. [PubMed] [Google Scholar]
- CHANCE B., WILLIAMS G. R. Respiratory enzymes in oxidative phosphorylation. VI. The effects of adenosine diphosphate on azide-treated mitochondria. J Biol Chem. 1956 Jul;221(1):477–489. [PubMed] [Google Scholar]
- CHANCE B., WILLIAMS G. R. The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem. 1956;17:65–134. doi: 10.1002/9780470122624.ch2. [DOI] [PubMed] [Google Scholar]
- FERNANDEZ-MORAN H. Cell-membrane ultrastructure. Low-temperature electron microsopy and x-ray diffraction studies of lipoprotein components in lamellar systems. Circulation. 1962 Nov;26:1039–1065. doi: 10.1161/01.cir.26.5.1039. [DOI] [PubMed] [Google Scholar]
- FROESE G. The respiration of ascites tumour cells at low oxygen concentrations. Biochim Biophys Acta. 1962 Mar 12;57:509–519. doi: 10.1016/0006-3002(62)91158-7. [DOI] [PubMed] [Google Scholar]
- Nicholls P. Oxidation and peroxidation. J Gen Physiol. 1965 Sep;49(1 Suppl):131–147. [PubMed] [Google Scholar]
- Parsons D. F. Mitochondrial Structure: Two Types of Subunits on Negatively Stained Mitochondrial Membranes. Science. 1963 May 31;140(3570):985–987. doi: 10.1126/science.140.3570.985. [DOI] [PubMed] [Google Scholar]
- Smith D. S. THE STRUCTURE OF FLIGHT MUSCLE SARCOSOMES IN THE BLOWFLY CALLIPHORA ERYTHROCEPHALA (DIPTERA). J Cell Biol. 1963 Oct 1;19(1):115–138. doi: 10.1083/jcb.19.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- YONETANI T. Studies on cytochrome oxidase. III. Improved preparation and some properties. J Biol Chem. 1961 Jun;236:1680–1688. [PubMed] [Google Scholar]