Cloning and mutational analysis of human malonyl-coenzyme A decarboxylase.

Malonyl coenzyme A (CoA) decarboxylase (E.C.4. 1.1.9) catalyzes the conversion of malonyl CoA to acetyl CoA. The metabolic role of malonyl CoA decarboxylase has not been fully defined, but deficiency of the enzyme has been associated with mild mental retardation, seizures, hypotonia, cardiomyopathy, vomiting, hypoglycemia, metabolic acidosis, and malonic aciduria. Here we report the isolation and sequencing of the human gene encoding malonyl CoA decarboxylase, and the identification of a mutation causing malonyl CoA decarboxylase deficiency. Human malonyl CoA decarboxylase cDNA sequences were identified by homology to the goose gene, and the intron/exon boundaries were determined by direct sequencing of a PAC clone containing the entire human gene. The 1479 basepair human cDNA is 70 percent identical to the goose sequence, and the intron/exon boundaries are completely conserved between the two species. The genetic mutation underlying malonyl CoA decarboxylase deficiency was determined in a patient with clinical features of this defect, malonic aciduria, and markedly reduced malonyl CoA decarboxylase activity.

[1]  M. Prentki,et al.  Molecular or Pharmacologic Perturbation of the Link between Glucose and Lipid Metabolism Is without Effect on Glucose-stimulated Insulin Secretion , 1998, The Journal of Biological Chemistry.

[2]  J. Williams,et al.  A new case of malonyl coenzyme A decarboxylase deficiency presenting with cardiomyopathy , 1997, European Journal of Pediatrics.

[3]  J. Goodman,et al.  The targeting and assembly of peroxisomal proteins: some old rules do not apply. , 1996, Trends in biochemical sciences.

[4]  R. W. Logan,et al.  Malonyl coenzyme A decarboxylase deficiency. , 1993, Archives of disease in childhood.

[5]  P. Kolattukudy,et al.  Cytoplasmic accumulation of a normally mitochondrial malonyl-CoA decarboxylase by the use of an alternate transcription start site. , 1992, Archives of biochemistry and biophysics.

[6]  P. Kolattukudy,et al.  Molecular cloning, nucleotide sequence, and tissue distribution of malonyl-CoA decarboxylase. , 1989, The Journal of biological chemistry.

[7]  P. Kolattukudy,et al.  Malonyl-CoA decarboxylase from Mycobacterium tuberculosis and Pseudomonas fluorescens. , 1979, Archives of biochemistry and biophysics.

[8]  P. Kolattukudy,et al.  Malonyl-CoA decarboxylase in rat brain mitochondria. , 1979, The International journal of biochemistry.

[9]  P. Kolattukudy,et al.  Dual sites of occurrence of malonyl-CoA decarboxylase and their possible functional significance in avian tissues. , 1979, Comparative biochemistry and physiology. B, Comparative biochemistry.

[10]  P. Kolattukudy,et al.  Malonyl-CoA decarboxylase from the mammary gland of lactating rat. Purification, properties and subcellular localization. , 1978, Biochimica et biophysica acta.

[11]  P. Kolattukudy,et al.  Malonyl-CoA decarboxylase from the uropygial gland of waterfowl: purification, properties, immunological comparison, and role in regulating the synthesis of multimethyl-branched fatty acids. , 1978, Archives of biochemistry and biophysics.

[12]  P. Kolattukudy,et al.  Purification and properties of malonyl-CoA decarboxylase from rat liver mitochondria and its immunological comparison with the enzymes from rat brain, heart, and mammary gland. , 1978, Archives of biochemistry and biophysics.

[13]  H. Scholte.  The intracellular and intramitochondrial distribution of malonyl-CoA decarboxylase and propionyl-CoA carboxylase in rat liver. , 1969, Biochimica et biophysica acta.