Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1182-1198 |
| Number of pages | 17 |
| Journal | Electrophoresis |
| Volume | 27 |
| Issue number | 5-6 |
| DOIs | |
| Publication status | Published - Mar 2006 |
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Keywords
- β-oxidation
- Mitochondria
- Neuromuscular pathology
- Proteomics
- Skeletal muscle
ASJC Scopus subject areas
- Clinical Biochemistry
Cite this
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. / 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.
In: Electrophoresis, Vol. 27, No. 5-6, 03.2006, p. 1182-1198.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Gianazza, Elisabetta
AU - Vergani, Lodovica
AU - Wait, Robin
AU - Brizio, Carmen
AU - Brambilla, Daniela
AU - Begum, Shajna
AU - Giancaspero, Teresa A.
AU - Conserva, Francesca
AU - Eberini, Ivano
AU - Bufano, Daniela
AU - Angelini, Corrado
AU - Pegoraro, Elena
AU - Tramontano, Anna
AU - Barile, Maria
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - β-oxidation
KW - Mitochondria
KW - Neuromuscular pathology
KW - Proteomics
KW - Skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=33645471734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645471734&partnerID=8YFLogxK
U2 - 10.1002/elps.200500687
DO - 10.1002/elps.200500687
M3 - Article
VL - 27
SP - 1182
EP - 1198
JO - Electrophoresis
JF - Electrophoresis
SN - 0173-0835
IS - 5-6
ER -