Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue

D. P. Kelly, J. J. Kim, J. J. Billadello, Bryan Hainline, T. W. Chu, A. W. Strauss

Research output: Contribution to journalArticle

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Abstract

Medium-chain acyl-CoA dehydrogenase (MCAD; acyl-CoA:(acceptor) 2,3-oxidoreductase, EC 1.3.99.3) is one of three similar enzymes that catalyze the initial step of fatty acid β-oxidation. Definition of the primary structure of MCAD and the tissue distribution of its mRNA is of biochemical and clinical importance because of the recent recognition of inherited MCAD deficiency in humans. The MCAD mRNA nucleotide sequence was determined from two overlapping cDNA clones isolated from human liver and placental cDNA libraries, respectively. The MCAD mRNA includes a 1263-base-pair coding region and a 738-base-pair 3'-nontranslated region. A partial amino acid sequence (137 residues) determined on peptides derived from MCAD purified from porcine liver confirmed the identity of the cDNA clone. Comparison of the amino acid sequence predicted from the human MCAD cDNA with the partial protein sequence of the porcine MCAD revealed a high degree (88%) of interspecies sequence identity. RNA blot analysis shows that MCAD mRNA is expressed in a variety of rat (2.2 kilobases) and human (2.4 kilobases) tissues. Blot hybridization of RNA prepared from cultured skin fibroblasts from a patient with MCAD deficiency disclosed that mRNA was present and of similar size to MCAD mRNA derived from control fibroblasts. The isolation and characterization of MCAD cDNA is an important step in the definition of the defect underlying MCAD deficiency and in understanding its metabolic consequences.

Original languageEnglish (US)
Pages (from-to)4068-4072
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number12
DOIs
StatePublished - 1987
Externally publishedYes

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Acyl-CoA Dehydrogenase
Messenger RNA
Enzymes
Complementary DNA
Base Pairing
Amino Acid Sequence
Swine
Clone Cells
Fibroblasts
RNA
Acyl Coenzyme A
Liver
Tissue Distribution
Gene Library
Oxidoreductases
Fatty Acids
Skin
Peptides
Medium chain acyl CoA dehydrogenase deficiency

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue. / Kelly, D. P.; Kim, J. J.; Billadello, J. J.; Hainline, Bryan; Chu, T. W.; Strauss, A. W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 84, No. 12, 1987, p. 4068-4072.

Research output: Contribution to journalArticle

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AU - Chu, T. W.

AU - Strauss, A. W.

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