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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jun;81(11):3529–3533. doi: 10.1073/pnas.81.11.3529

31P NMR study of improvement in oxidative phosphorylation by vitamins K3 and C in a patient with a defect in electron transport at complex III in skeletal muscle.

S Eleff, N G Kennaway, N R Buist, V M Darley-Usmar, R A Capaldi, W J Bank, B Chance
PMCID: PMC345542  PMID: 6587367

Abstract

The bioenergetic capacity of skeletal muscle in a 17-year-old patient with a severe defect in complex III of the electron transport chain has been examined by 31P NMR measurements of the molar ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Resting ratios were 1.3-2.5, which can be compared with roughly 8.6 for a young, normal female control at rest. Quantitative evaluation of the activity of oxidative metabolism was afforded by the rate of recovery of PCr/Pi from exercise and was found to be 2.5% of normal. After administration of menadione and ascorbate, we found a 21-fold increase of the recovery rate relative to the pretherapy value, to within 56% of the recovery rate of the young female control. Thus, NMR examinations of skeletal muscle at rest and in recovery from activity document marked improvement to specific drug therapy in the electron transport capabilities and the ATP synthesis rate of a patient with a deficiency in a cytochrome b-containing complex III. Improvements in functional ability, although not as dramatic as biochemical changes, are also apparent.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CHANCE B., HOLLUNGER G. Energy-linked reduction of mitochondrial pyridine nucleotide. Nature. 1960 Mar 5;185:666–672. doi: 10.1038/185666a0. [DOI] [PubMed] [Google Scholar]
  2. Chance B., Eleff S., Bank W., Leigh J. S., Jr, Warnell R. 31P NMR studies of control of mitochondrial function in phosphofructokinase-deficient human skeletal muscle. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7714–7718. doi: 10.1073/pnas.79.24.7714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chance B., Eleff S., Leigh J. S., Jr, Sokolow D., Sapega A. Mitochondrial regulation of phosphocreatine/inorganic phosphate ratios in exercising human muscle: a gated 31P NMR study. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6714–6718. doi: 10.1073/pnas.78.11.6714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Darley-Usmar V. M., Kennaway N. G., Buist N. R., Capaldi R. A. Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5103–5106. doi: 10.1073/pnas.80.16.5103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edwards R. H., Dawson M. J., Wilkie D. R., Gordon R. E., Shaw D. Clinical use of nuclear magnetic resonance in the investigation of myopathy. Lancet. 1982 Mar 27;1(8274):725–731. doi: 10.1016/s0140-6736(82)92635-6. [DOI] [PubMed] [Google Scholar]
  6. McCord J. M., Fridovich I. The utility of superoxide dismutase in studying free radical reactions. II. The mechanism of the mediation of cytochrome c reduction by a variety of electron carriers. J Biol Chem. 1970 Mar 25;245(6):1374–1377. [PubMed] [Google Scholar]
  7. Nosoh Y., Kajioka J., Itoh M. Effect of menadione on the electron transport pathway of yeast mitochondria. Arch Biochem Biophys. 1968 Sep 20;127(1):1–6. doi: 10.1016/0003-9861(68)90193-8. [DOI] [PubMed] [Google Scholar]
  8. Ross B. D., Radda G. K., Gadian D. G., Rocker G., Esiri M., Falconer-Smith J. Examination of a case of suspected McArdle's syndrome by 31P nuclear magnetic resonance. N Engl J Med. 1981 May 28;304(22):1338–1342. doi: 10.1056/NEJM198105283042206. [DOI] [PubMed] [Google Scholar]
  9. SANADI D. R. ON THE MECHANISM OF OXIDATIVE PHOSPHORYLATION. IX. ENERGY-DEPENDENT REDUCTION OF NICOTINAMIDE ADENINE DINUCLEOTIDE BY ASCORBATE AND UBIQUINONE OR MENADIONE. Biochim Biophys Acta. 1964 Aug 26;89:367–369. doi: 10.1016/0926-6569(64)90231-7. [DOI] [PubMed] [Google Scholar]
  10. Warshaw J. B., Lam K. W., Sanadi D. R. Studies on oxidative phosphorylation. XI. Energy-dependent reduction of diphosphophyridine nucleotide by ene-diol compounds in the presence of dyes. Arch Biochem Biophys. 1966 Aug;115(2):307–311. doi: 10.1016/0003-9861(66)90279-7. [DOI] [PubMed] [Google Scholar]
  11. Williamson D. H., Lund P., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J. 1967 May;103(2):514–527. doi: 10.1042/bj1030514. [DOI] [PMC free article] [PubMed] [Google Scholar]

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