Deficiencies of NADH and succinate dehydrogenases in degenerative diseases and myopathies.
This paper examines the experimental foundations of reports in the literature on mitochondrial diseases involving Complexes I and II of the respiratory chain. Many of the reports may be questioned on the basis of the assay conditions used which disregard established knowledge of the precautions required for valid activity measurements. In addition, some findings are open to question because of the experimental material chosen for the study, such as the measurement of NADH oxidase activity in platelets in Parkinson's disease, which affects selectively the dopamine neurons, or the use of autopsy material stored for prolonged periods during which post-mortem changes may have occurred. Deficiencies claimed to involve several components of the respiratory chain may reflect indirect effects, such as defects in the synthesis of iron-sulfur clusters or in the availability of iron, rather than mutations in the genes coding for the deficient enzymes. Nevertheless, there are a few instances reported of Complex II deficiency free from such criticisms. As to Complex I, idiopathic Parkinsonism appears to involve a documentable decline in the activity of this enzyme. Using the model system provided by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces biochemical, pharmacological, and clinical syndromes closely resembling Parkinsonism, the etiology of the disease is examined.
Singer
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TP
Department of Biochemistry and Biophysics, University of California, San Francisco, USA.
Ramsay
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RR
Ackrell
B A
BA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D002417:Cattle; D042963:Electron Transport Complex II; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000201:enzymology; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency / Q000235:genetics; D009245:NADH Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D009468:Neuromuscular Diseases / Q000201:enzymology* / Q000235:genetics; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics; D010300:Parkinson Disease / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D010302:Parkinson Disease, Secondary / Q000201:enzymology; D013385:Succinate Dehydrogenase / Q000172:deficiency* / Q000235:genetics
D005609:Free Radicals; D009097:Multienzyme Complexes; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D009245:NADH Dehydrogenase