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.
Gao
J
J
The Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Waber
L
L
Bennett
M J
MJ
Gibson
K M
KM
Cohen
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002262:Carboxy-Lyases / Q000172:deficiency / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology / Q000235:genetics; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005777:Geese; D006801:Humans; D007223:Infant; D008297:Male; D008314:Malonates / Q000652:urine; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018076:DNA, Complementary; D008314:Malonates; C030290:malonic acid; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase