cDNA cloning of the E1α subunit of the branched-chain α-keto acid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease

B. Zhang, M. J. Kuntz, G. W. Goodwin, Howard Edenberg, David Crabb, Robert Harris

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have cloned cDNAs encoding human and rat liver BCKDH E1α subunits and deduced the primary structure of the mature protein. The sequences of the cDNA and protein are highly conserved between the two species. Significant sequence similarity has also been found between human BCKDH and PDH E1α subunits. We have studied the molecular basis of MSUD by determining the enzyme activity and levels of BCKDH protein and mRNA, and by enzymatic amplification and sequencing of BCKDH E1α-specific mRNA, from an MSUD patient and his parents. Different mutant alleles were identified in the two parents. The patient was a compound heterozygote, inheriting an allele encoding an abnormal E1α from the father and an allele containing a defect in regulation from the mother. Our results demonstrate that a case of MSUD was caused by structural and regulatory mutations involving the E1α subunit.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalAnnals of the New York Academy of Sciences
Volume573
DOIs
StatePublished - 1989

Fingerprint

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Maple Syrup Urine Disease
Cloning
Organism Cloning
Complementary DNA
Alleles
Parents
Messenger RNA
Proteins
Enzyme activity
Heterozygote
Fathers
Liver
Amplification
Rats
Amino Acid Sequence
Mothers
Defects
Mutation
Enzymes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "cDNA cloning of the E1α subunit of the branched-chain α-keto acid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease",
abstract = "We have cloned cDNAs encoding human and rat liver BCKDH E1α subunits and deduced the primary structure of the mature protein. The sequences of the cDNA and protein are highly conserved between the two species. Significant sequence similarity has also been found between human BCKDH and PDH E1α subunits. We have studied the molecular basis of MSUD by determining the enzyme activity and levels of BCKDH protein and mRNA, and by enzymatic amplification and sequencing of BCKDH E1α-specific mRNA, from an MSUD patient and his parents. Different mutant alleles were identified in the two parents. The patient was a compound heterozygote, inheriting an allele encoding an abnormal E1α from the father and an allele containing a defect in regulation from the mother. Our results demonstrate that a case of MSUD was caused by structural and regulatory mutations involving the E1α subunit.",
author = "B. Zhang and Kuntz, {M. J.} and Goodwin, {G. W.} and Howard Edenberg and David Crabb and Robert Harris",
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T1 - cDNA cloning of the E1α subunit of the branched-chain α-keto acid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease

AU - Zhang, B.

AU - Kuntz, M. J.

AU - Goodwin, G. W.

AU - Edenberg, Howard

AU - Crabb, David

AU - Harris, Robert

PY - 1989

Y1 - 1989

N2 - We have cloned cDNAs encoding human and rat liver BCKDH E1α subunits and deduced the primary structure of the mature protein. The sequences of the cDNA and protein are highly conserved between the two species. Significant sequence similarity has also been found between human BCKDH and PDH E1α subunits. We have studied the molecular basis of MSUD by determining the enzyme activity and levels of BCKDH protein and mRNA, and by enzymatic amplification and sequencing of BCKDH E1α-specific mRNA, from an MSUD patient and his parents. Different mutant alleles were identified in the two parents. The patient was a compound heterozygote, inheriting an allele encoding an abnormal E1α from the father and an allele containing a defect in regulation from the mother. Our results demonstrate that a case of MSUD was caused by structural and regulatory mutations involving the E1α subunit.

AB - We have cloned cDNAs encoding human and rat liver BCKDH E1α subunits and deduced the primary structure of the mature protein. The sequences of the cDNA and protein are highly conserved between the two species. Significant sequence similarity has also been found between human BCKDH and PDH E1α subunits. We have studied the molecular basis of MSUD by determining the enzyme activity and levels of BCKDH protein and mRNA, and by enzymatic amplification and sequencing of BCKDH E1α-specific mRNA, from an MSUD patient and his parents. Different mutant alleles were identified in the two parents. The patient was a compound heterozygote, inheriting an allele encoding an abnormal E1α from the father and an allele containing a defect in regulation from the mother. Our results demonstrate that a case of MSUD was caused by structural and regulatory mutations involving the E1α subunit.

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