title: Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways.
abstract: Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) and glutamate dehydrogenase (GDH) explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST) and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1) from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Srinivas B
authors.initials: SB
authors.lastname: Narayan
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Master
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Sireci
authors.forename: Charlene
authors.initials: C
authors.lastname: Bierl
authors.forename: Paige E
authors.initials: PE
authors.lastname: Stanley
authors.forename: Changhong
authors.initials: C
authors.lastname: Li
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stanley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bennett
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000737:chemistry / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D005634:Fructose-Bisphosphate Aldolase; D002222:Carbamoyl-Phosphate Synthase (Ammonia)