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Comparative biochemical studies in fibroblasts from patients with different forms of Leigh syndrome
Author(s) -
VazquezMemije M. E.,
Shanske S.,
Santorelli F. M.,
KranzEble P.,
Davidson E.,
De Vivo D. C.,
DiMauro S.
Publication year - 1996
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799347
Subject(s) - leigh disease , cytochrome c oxidase , bioenergetics , mitochondrion , respiratory chain , enzyme , atp synthase , oxidative phosphorylation , mitochondrial respiratory chain , biochemistry , pyruvate dehydrogenase complex , succinate dehydrogenase , biology , adenosine triphosphate , atpase , mutation , medicine , gene
Summary We have compared respiratory chain enzyme activities, ATP synthesis, and ATP hydrolysis in cultured fibroblast mitochondria from patients with Leigh syndrome (LS) due to: (i) cytochrome oxidase (COX) deficiency (#6); (ii) pyruvate dehydrogenase complex (PDHC) deficiency (#4); and (iii) maternally inherited LS (MILS) with the T8993G mutation in the ATPase 6 gene of mtDNA (#5). Enzyme activities were normal in patients with MILS and variably decreased in those with COX and PDHC deficiency. ATP hydrolysis was normal or mildly decreased in all three groups. In contrast, ATP synthesis was decreased in all patients but more markedly in those with MILS, and especially with pyruvate/malate as substrate. These studies show that impaired ATP production is the common feature of all three forms of LS, but it is both more severe and more specific in MILS, consistent with the genetic defect.