An acyl-CoA dehydrogenase microplate activity assay using recombinant porcine electron transfer flavoprotein.


Journal

Analytical biochemistry
ISSN: 1096-0309
Titre abrégé: Anal Biochem
Pays: United States
ID NLM: 0370535

Informations de publication

Date de publication:
15 09 2019
Historique:
received: 26 04 2019
revised: 03 06 2019
accepted: 03 06 2019
pubmed: 14 6 2019
medline: 20 3 2020
entrez: 14 6 2019
Statut: ppublish

Résumé

Acyl-CoA dehydrogenases (ACADs) play key roles in the mitochondrial catabolism of fatty acids and branched-chain amino acids. All nine characterized ACAD enzymes use electron transfer flavoprotein (ETF) as their redox partner. The gold standard for measuring ACAD activity is the anaerobic ETF fluorescence reduction assay, which follows the decrease of pig ETF fluorescence as it accepts electrons from an ACAD in vitro. Although first described 35 years ago, the assay has not been widely used due to the need to maintain an anaerobic assay environment and to purify ETF from pig liver mitochondria. Here, we present a method for expressing recombinant pig ETF in E coli and purifying it to homogeneity. The recombinant protein is virtually pure after one chromatography step, bears higher intrinsic fluorescence than the native enzyme, and provides enhanced activity in the ETF fluorescence reduction assay. Finally, we present a simplified protocol for removing molecular oxygen that allows adaption of the assay to a 96-well plate format. The availability of recombinant pig ETF and the microplate version of the ACAD activity assay will allow wide application of the assay for both basic research and clinical diagnostics.

Identifiants

pubmed: 31194945
pii: S0003-2697(19)30408-7
doi: 10.1016/j.ab.2019.06.003
pmc: PMC6661201
mid: NIHMS1532453
pii:
doi:

Substances chimiques

Electron-Transferring Flavoproteins 0
Fatty Acids 0
Recombinant Proteins 0
Acyl-CoA Dehydrogenases EC 1.3.-

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

113332

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK045482
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078775
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK090242
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109907
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Yuxun Zhang (Y)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Al-Walid Mohsen (AW)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Catherine Kochersperger (C)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Keaton Solo (K)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Alexandra V Schmidt (AV)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Jerry Vockley (J)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Eric S Goetzman (ES)

Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. Electronic address: eric.goetzman@chp.edu.

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