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Coordinated and reversible reduction of enzymes involved in terminal oxidative metabolism in skeletal muscle mitochondria from a riboflavin‐responsive, multiple acyl‐CoA dehydrogenase deficiency patient
Author(s) -
Gianazza Elisabetta,
Vergani Lodovica,
Wait Robin,
Brizio Carmen,
Brambilla Daniela,
Begum Shajna,
Giancaspero Teresa A.,
Conserva Francesca,
Eberini Ivano,
Bufano Daniela,
Angelini Corrado,
Pegoraro Elena,
Tramontano Anna,
Barile Maria
Publication year - 2006
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200500687
Subject(s) - riboflavin , flavin group , biochemistry , cofactor , flavin adenine dinucleotide , mitochondrion , skeletal muscle , oxidative phosphorylation , flavoprotein , carnitine , enzyme , succinate dehydrogenase , biology , dehydrogenase , respiratory chain , metabolism , endocrinology
In this case report we studied alterations in mitochondrial proteins in a patient suffering from recurrent profound muscle weakness, associated with ethylmalonic‐adipic aciduria, who had benefited from high dose of riboflavin treatment. Morphological and biochemical alterations included muscle lipid accumulation, low muscle carnitine content, reduction in fatty acid β‐oxidation and reduced activity of complexes I and II of the respiratory chain. Riboflavin therapy partially or totally reversed these symptoms and increased the level of muscle flavin adenine dinucleotide, suggesting that aberrant flavin cofactor metabolism accounted for the disease. Proteomic investigation of muscle mitochondria revealed decrease or absence of several flavoenzymes, enzymes related to flavin cofactor‐dependent mitochondrial pathways and mitochondrial or mitochondria‐associated calcium‐binding proteins. All these deficiencies were completely rescued after riboflavin treatment. This study indicates for the first time a profound involvement of riboflavin/flavin cofactors in modulating the level of a number of functionally coordinated polypeptides involved in fatty acyl‐CoA and amino acid metabolism, extending the number of enzymatic pathways altered in riboflavin‐responsive multiple acyl‐CoA dehydrogenase deficiency.