Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients

Toshifumi Aoyama, Masayoshi Souri, Seiichi Ushikubo, Takehiko Kamijo, Seiji Yamaguchi, Richard I. Kelley, William J. Rhead, Kimiaki Uetake, Kay Tanaka, Takashi Hashimoto

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130 Scopus citations


Mitochondrial very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) was purified from human liver. The molecular masses of the native enzyme and the subunit were estimated to be 154 and 70 kD, respectively. The enzyme was found to catalyze the major part of mitochondrial palmitoyl-coenzyme A dehydrogenation in liver, heart, skeletal muscle, and skin fibroblasts (89- 97, 86-99, 96-99, and 78-87%, respectively). Skin fibroblasts from 26 patients suspected of having a disorder of mitochondrial β-oxidation were analyzed for VLCAD protein using immunoblotting, and 7 of them contained undetectable or trace levels of the enzyme. The seven deficient fibroblast lines were characterized by measuring acyl-coenzyme A dehydrogenation activities, overall palmitic acid oxidation, and VLCAD protein synthesis using pulse-chase, further confirming the diagnosis of VLCAD deficiency. These results suggested the heterogenous nature of the mutations causing the deficiency in the seven patients. Clinically, all patients with VLCAD deficiency exhibited cardiac disease. At least four of them presented with hypertrophic cardiomyopathy. This frequency (>57%) was much higher than that observed in patients with other disorders of mitochondrial long-chain fatty acid oxidation that may be accompanied by cardiac disease in infants.

Original languageEnglish (US)
Pages (from-to)2465-2473
Number of pages9
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Jun 1995
Externally publishedYes


  • fatty acid β-oxidation
  • hypertrophic cardiomyopathy
  • mitochondria
  • palmitoyl-coenzyme A
  • pulse-chase experiment

ASJC Scopus subject areas

  • Medicine(all)


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