Faculty Collaboration Database

Catalytic defect of medium-chain acyl-coenzyme A dehydrogenase deficiency. Lack of both cofactor responsiveness and biochemical heterogeneity in eight patients. J Clin Invest 1985 Sep;76(3):963-9

Date

09/01/1985

Pubmed ID

3840178

Pubmed Central ID

PMC423960

DOI

10.1172/JCI112096

Scopus ID

2-s2.0-0022359510 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCADH; EC 1.3.99.3) deficiency (MCD) is an inborn error of beta-oxidation. We measured 3H2O formed by the dehydrogenation of [2,3-3H]acyl-CoAs in a 3H-release assay. Short-chain acyl-CoA dehydrogenase (SCADH; EC 1.3.99.2), MCADH, and isovaleryl-CoA dehydrogenase (IVDH; EC 1.3.99.10) activities were assayed with 100 microM [2,3-3H]butyryl-, -octanoyl-, and -isovaleryl-CoAs, respectively, in fibroblasts cultured from normal controls and MCD patients. Without the artificial electron acceptor phenazine methosulfate (PMS), MCADH activity in fibroblast mitochondrial sonic supernatants (MS) was 54% of control in two MCD cell lines (P less than 0.05). Addition of 10 mM PMS raised control acyl-CoA dehydrogenase activities 16-fold and revealed MCADH and SCADH activities to be 5 (P less than 0.01) and 73% (P greater than 0.1) of control, respectively. Thus, the catalytic defect in MCD involves substrate binding and/or dehydrogenation by MCADH and not the subsequent reoxidation of reduced MCADH by electron acceptors. 20 microM flavin adenine dinucleotide (FAD) did not stimulate MCD MCADH activity in either the 3H-release or electron-transfer(ring) flavoprotein-linked dye-reduction assays. Mixing experiments revealed no MCADH inhibitor in MCD MS; IVDH activities were identical in both control and MCD MS. In postmortem liver MS from another MCD patient, 3H2O formation from [2,3-3H]octanoyl-CoA was 15% of control. When 3H2O formation was assayed with 200 microM [2,3-3H]acyl-CoAs, 15 mM PMS, and 20 microM FAD in fibroblast sonic supernatants from seven MCD cell lines, SCADH, MCADH, and IVDH activities were 72-112% (P greater than 0.1), 4-9% (P less than 0.01), and 86-135% (P greater than 0.1) of control, respectively, revealing no significant biochemical heterogeneity among these patients.

Author List

Amendt BA, Rhead WJ

Author

William Rhead MD, PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acyl Coenzyme A
Acyl-CoA Dehydrogenases
Adult
Fibroblasts
Flavin-Adenine Dinucleotide
Hemiterpenes
Humans
Infant
Isovaleryl-CoA Dehydrogenase
Lipid Metabolism, Inborn Errors
Male
Methylphenazonium Methosulfate
Mitochondria, Liver
Oxidoreductases
Oxidoreductases Acting on CH-CH Group Donors
Pentanoic Acids
Subcellular Fractions