Defective succinic semialdehyde dehydrogenase activity in 4-hydroxybutyric aciduria.
Succinic semialdehyde dehydrogenase deficiency has been demonstrated in a fourth patient with 4-hydroxybutyric aciduria. Lysates of freshly isolated lymphocytes and cultured lymphoblasts of the patient had much lower than control activity in the conversion of U-14C-4-aminobutyric acid to 14C-succinic acid in an assay designed to estimate succinic semialdehyde dehydrogenase utilizing endogenous 4-aminobutyrate transaminase. Lymphocyte and lymphoblast lysates of the patient accumulated U-14C-succinic semialdehyde when incubated with U-14C-4-aminobutyric acid and NAD+ whereas none could be detected in controls. Assays using U-14C-succinic semialdehyde as substrate for succinic semialdehyde dehydrogenase in lysates of cultured lymphoblasts characterized the patient as having a severe deficiency of succinic semialdehyde dehydrogenase. The data indicate that defective activity of succinic semialdehyde dehydrogenase is responsible for 4-hydroxybutyric aciduria.
D000612:4-Aminobutyrate Transaminase / Q000097:blood; D000328:Adult; D002262:Carboxy-Lyases / Q000097:blood; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000172:deficiency*; D006885:Hydroxybutyrates / Q000652:urine*; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology; D043586:Methylmalonyl-CoA Decarboxylase; D012978:Sodium Oxybate / Q000652:urine*
D006885:Hydroxybutyrates; D012978:Sodium Oxybate; D006884:Hydroxybutyrate Dehydrogenase; C019416:4-hydroxybutyrate dehydrogenase; D000612:4-Aminobutyrate Transaminase; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase