Role of short-chain hydroxyacyl CoA dehydrogenases in SCHAD deficiency.

Journal article

Short-chain hydroxyacyl CoA dehydrogenase deficiency is an ill-defined, severe pediatric disorder of mitochondrial fatty acid beta-oxidation of short-chain hydroxyacyl CoAs. To understand the relative contributions of the two known short-chain hydroxyacyl CoA dehydrogenases (HADH) tissue biopsies of six distinct family individuals were analyzed and kinetic parameters were compared. Steady-state kinetic constants for HADH 1 and HADH 2 suggest that type 1 is the major enzyme involved in mitochondrial beta-oxidation of short-chain hydroxyacyl-CoAs. Two patients are heterozygous carriers of a HADH 1 polymorphism, whereas no mutation is detected in the HADH 2 gene of all patients. The data suggest that protein interactions rather than HADH mutations are responsible for the disease phenotype. Pull-down experiments of recombinant HADH 1 and 2 with human mitochondrial extracts reveal two proteins interacting with HADH 1, one of which was identified as glutamate dehydrogenase. This association provides a possible link between fatty acid metabolism and the hyperinsulinism/hyperammonia syndrome.

Authors: Filling, C; Keller, B; Hirschberg, D; Marschall, H; Jörnvall, H

• Publication status: Published
• Journal: Biochemical and biophysical research communications
• Volume: 368
• Issue: 1
• Pages: 6-11
• Publication date: 2008-03-01
• DOI: 10.1016/j.bbrc.2007.10.188
• EISSN: 1090-2104
• ISSN: 0006-291X
• Language: English
• Keywords: Humans; Protein Binding; Mitochondria, Liver; Kinetics; Enoyl-CoA Hydratase