Immunochemical characterization of variant long-chain acyl-CoA dehydrogenase in cultured fibroblasts from nine patients with long-chain acyl-CoA dehydrogenase deficiency

Yasuhiro Indo, Paul M. Coates, Daniel Hale, Kay Tanaka

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepatoand cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain acyl-CoA dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain acyl-CoA dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency.

Original languageEnglish (US)
Pages (from-to)211-215
Number of pages5
JournalPediatric Research
Volume30
Issue number3
DOIs
StatePublished - Jan 1 1991

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Long-Chain Acyl-CoA Dehydrogenase
Fibroblasts
Acyl-CoA Dehydrogenase
Point Mutation
Long-chain acyl-CoA dehydrogenase deficiency
Cell Line
Mitochondrial Diseases
Molecular Pathology
Muscle Weakness
Cardiomegaly

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

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title = "Immunochemical characterization of variant long-chain acyl-CoA dehydrogenase in cultured fibroblasts from nine patients with long-chain acyl-CoA dehydrogenase deficiency",
abstract = "Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepatoand cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain acyl-CoA dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain acyl-CoA dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency.",
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Immunochemical characterization of variant long-chain acyl-CoA dehydrogenase in cultured fibroblasts from nine patients with long-chain acyl-CoA dehydrogenase deficiency. / Indo, Yasuhiro; Coates, Paul M.; Hale, Daniel; Tanaka, Kay.

In: Pediatric Research, Vol. 30, No. 3, 01.01.1991, p. 211-215.

Research output: Contribution to journalArticle

TY - JOUR

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N2 - Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepatoand cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain acyl-CoA dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain acyl-CoA dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency.

AB - Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepatoand cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain acyl-CoA dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain acyl-CoA dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency.

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