Activity of biotin-dependent and GABA metabolizing enzymes in chorionic villus samples: potential for 1st trimester prenatal diagnosis.
We have documented the presence of five mitochondrial enzymes in samples of chorionic villus tissue and measured the levels of activity. Three of the enzymes catalyse biotin-dependent reactions. These are propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase and pyruvate carboxylase. The other enzymes, 4-aminobutyric acid aminotransferase and succinic semialdehyde dehydrogenase, are involved in the degradation of the central inhibitory neurotransmitter GABA. Distinct diseases in which there is deficiency of each of these enzymes have been documented in man. Significant levels of activity were observed for all five enzymes in chorionic villus tissue. This methodology should permit early prenatal diagnosis of deficiencies of these enzymes by chorionic villus biopsy in the first trimester.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D001706:Biopsy; D001710:Biotin / Q000494:pharmacology*; D019735:Carbon-Carbon Ligases; D002262:Carboxy-Lyases / Q000378:metabolism; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology; D043586:Methylmalonyl-CoA Decarboxylase; D008928:Mitochondria / Q000201:enzymology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis; D011766:Pyruvate Carboxylase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D001710:Biotin; D006884:Hydroxybutyrate Dehydrogenase; C019416:4-hydroxybutyrate dehydrogenase; D000612:4-Aminobutyrate Transaminase; D002262:Carboxy-Lyases; D008025:Ligases; D019735:Carbon-Carbon Ligases; D011766:Pyruvate Carboxylase; C021573:methylcrotonoyl-CoA carboxylase; D043586:Methylmalonyl-CoA Decarboxylase