Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways.
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 hyperinsulini...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3322157?pdf=render |
| _version_ | 1818061898429497344 |
|---|---|
| author | Srinivas B Narayan Stephen R Master Anthony N Sireci Charlene Bierl Paige E Stanley Changhong Li Charles A Stanley Michael J Bennett |
| author_facet | Srinivas B Narayan Stephen R Master Anthony N Sireci Charlene Bierl Paige E Stanley Changhong Li Charles A Stanley Michael J Bennett |
| author_sort | Srinivas B Narayan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T13:55:38Z |
| format | Article |
| id | doaj.art-cd736cac40ee4b72bcf6b3c8dfebf2d7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T13:55:38Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cd736cac40ee4b72bcf6b3c8dfebf2d72022-12-22T01:46:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3504810.1371/journal.pone.0035048Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways.Srinivas B NarayanStephen R MasterAnthony N SireciCharlene BierlPaige E StanleyChanghong LiCharles A StanleyMichael J BennettProteins 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.http://europepmc.org/articles/PMC3322157?pdf=render |
| spellingShingle | Srinivas B Narayan Stephen R Master Anthony N Sireci Charlene Bierl Paige E Stanley Changhong Li Charles A Stanley Michael J Bennett Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. PLoS ONE |
| title | Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. |
| title_full | Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. |
| title_fullStr | Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. |
| title_full_unstemmed | Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. |
| title_short | Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. |
| title_sort | short chain 3 hydroxyacyl coenzyme a dehydrogenase associates with a protein super complex integrating multiple metabolic pathways |
| url | http://europepmc.org/articles/PMC3322157?pdf=render |
| work_keys_str_mv | AT srinivasbnarayan shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT stephenrmaster shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT anthonynsireci shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT charlenebierl shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT paigeestanley shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT changhongli shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT charlesastanley shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways AT michaeljbennett shortchain3hydroxyacylcoenzymeadehydrogenaseassociateswithaproteinsupercomplexintegratingmultiplemetabolicpathways |