Journal article
Catalytic defect of medium-chain acyl-coenzyme A dehydrogenase deficiency: lack of both cofactor responsiveness and biochemical heterogeneity in eight patients
The Journal of clinical investigation, Vol.76(3), pp.963-969
1985
DOI: 10.1172/JCI112096
PMCID: PMC423960
PMID: 3840178
Abstract
Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCADH; EC 1.3.99.3) deficiency (MCD) is an inborn error of β-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 μM[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<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<0.01) and 73% (P>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 μM 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 μM [2,3-3H]acyl-CoAs, 15 mM PMS, and 20 μM FAD in fibroblast sonic supernatants from seven MCD cell lines, SCADH, MCADH, and IVDH activities were 72-112% (p>0.1), 4-9% (P<0.01), and 86-135% (P>0.1) of control, respectively, revealing no significant biochemical heterogeneity among these patients.
Details
- Title: Subtitle
- Catalytic defect of medium-chain acyl-coenzyme A dehydrogenase deficiency: lack of both cofactor responsiveness and biochemical heterogeneity in eight patients
- Creators
- Brad A Amendt - Univ. Iowa, dep. pediatricsWilliam J Rhead - Univ. Iowa, dep. pediatrics
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.76(3), pp.963-969
- DOI
- 10.1172/JCI112096
- PMID
- 3840178
- PMCID
- PMC423960
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 1985
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284457202771
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