HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Lactic acidosis and mitochondrial myopathy associated with deficiency of several components of complex III of the respiratory chain.

Abstract
We have studied a 17-year-old girl with lactic acidosis (3-18 mEq/liter) and progressive muscle weakness since 9 years of age. Morphological findings in muscle were of a typical ragged red myopathy with multiple collections of bizarre mitochondria, some containing paracrystalline inclusions. The carnitine content of serum and muscle was normal, as were the activities of carnitine palmitoyltransferase, carnitine octanoyltransferase, and carnitine acetyltransferase in the patient's muscle. Measurement of the enzymes of oxidative phosphorylation in both crude muscle homogenates and mitochondrial fractions showed close to normal activities of cytochrome c oxidase, succinate dehydrogenase, and ATPase. In contrast, succinate cytochrome c reductase activity was greatly reduced in the patient, being 0.035 mumol/min/g tissue in whole muscle (controls 1.16 +/- 0.47 mumol/min/g tissue) and 8 nmol/min/mg protein in the mitochondria (control, 340 nmol/min/mg protein). Rotenonesensitive NADH-cytochrome c reductase was also undetectable in the patient's mitochondria. Spectral analysis of cytochromes showed decrease of reducible cytochrome b to 16% of the control. These results indicate a defect of ubiquinol-cytochrome c reductase or the cytochrome bc1 segment (complex III) of the electron transport chain. Antibody-binding studies of the individual components of complex III showed additional deficiencies of core proteins I and II and peptide VI, indicating a more widespread defect of complex III than was evident from spectral analysis and enzyme activity measurements alone. Urine organic acid analysis after fasting and following a medium chain triglyceride load showed unusually high levels of lactate and 3-hydroxybutyrate, lower than expected levels of acetoacetate and dicarboxylic acids, and the presence of several other metabolites suggesting a disturbed citric acid cycle and redox state.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsN G Kennaway, N R Buist, V M Darley-Usmar, A Papadimitriou, S Dimauro, R I Kelley, R A Capaldi, N K Blank, A D'Agostino
JournalPediatric research (Pediatr Res) Vol. 18 Issue 10 Pg. 991-9 (Oct 1984) ISSN: 0031-3998 [Print] United States
PMID6093035 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Lactates
  • Multienzyme Complexes
  • Succinate Cytochrome c Oxidoreductase
  • Succinate Dehydrogenase
  • NADH, NADPH Oxidoreductases
  • Quinone Reductases
  • NADH Dehydrogenase
  • Electron Transport Complex III
Topics
  • Acidosis (enzymology)
  • Adolescent
  • Biopsy
  • Electron Transport Complex III
  • Female
  • Humans
  • Lactates (blood)
  • Microscopy, Electron
  • Mitochondria, Muscle (enzymology, ultrastructure)
  • Multienzyme Complexes (deficiency)
  • Muscles (enzymology, pathology)
  • Muscular Diseases (enzymology, pathology)
  • NADH Dehydrogenase (deficiency)
  • NADH, NADPH Oxidoreductases (deficiency)
  • Quinone Reductases (deficiency)
  • Succinate Cytochrome c Oxidoreductase (deficiency)
  • Succinate Dehydrogenase (deficiency)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: