Absence of immunoreactive enzyme protewin in short‐chain acylcoenzyme a dehydrogenase deficiency

Farnsworth, L.; Shepherd, I. M.; Johnson, Margaret; Bindoff, Laurence A.; Turnbull, D. M.

doi:10.1002/ana.410280520

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…Although Turnbull et a/. (9) and Farnsworth et al (10) reported a human patient with apparent muscular SCAD deficiency, our observations argue against the presence of tissue-specific SCAD isoforms in mammals.…”

contrasting

confidence: 68%

“…Carole Hall and potential explanation for the biochemical findings in this patient Colin Thorpe for provision of the pure enzymes and Dr. Kay would involve a mutation of a muscle-specific SCAD isozyme, Tanaka for his advice and support. although there is no direct evidence to support this possibility (9,10). We found that fibroblasts from this patient had normal REFERENCES SCAD and MCAD activities and oxidized both [9'10(n)-…”

mentioning

confidence: 73%

“…and Farnsworth et al (10) reported an adult patient with an isolated muscular deficiency of SCAD activity and antigen. A…”

Section: Imrnunochemical Studies Of Scad and Mcadmentioning

confidence: 99%

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Short-Chain Acyl-Coenzyme A Dehydrogenase Activity, Antigen, and Biosynthesis Are Absent in the BALB/cByJ Mouse

et al. 1992

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ABSTRACT. BALB/cByJ (J) mice have short-chain acylCoA dehydrogenase (SCAD) deficiency and an organic aciduria similar to that of human SCAD deficiency.[9,10(n)-3H]-and 115,16(n)-3H]palmitate oxidations in J mouse fibroblasts were 96 and 35% of control, respectively, consistent with an isolated SCAD defect. Acyl-CoA dehydrogenase activities were assayed in muscle and fibroblast mitochondria from BALB/cBy controls (Y) and SCADdeficient J mice. Medium-chain acyl-CoA dehydrogenase (MCAD) activities were comparable in both J and Y mice from all tissues. In the presence of MCAD antiserum, SCAD activities in J mice were undetectable in both tissues. Apparent Km and V,,, values in liver mitochondria suggested a somewhat increased affinity of MCAD for butyryl-CoA in J mice, as compared with MCAD from other species. Immunoblot studies using mitochondria revealed identical apparent SCAD molecular weight in liver, muscle, and fibroblasts from Y mice and no detectable SCAD antigen in J mice; MCAD antigen was detected in comparable amounts from both Y and J mice. Radiolabeling and immunoprecipitation studies in J mouse fibroblasts revealed no SCAD synthesis, but normal MCAD synthesis. These data argue against the existence of tissue-specific SCAD isoforms in the mouse and confirm that this mouse strain is a model for the human organic aciduria resulting from this B-oxidation defect. (Pediatr Res 31: 552-556, 1992) Abbreviations SCAD, short-chain acyl-CoA dehydrogenase MCAD, medium-chain acyl-CoA dehydrogenase J, BALB/cByJ Y, BALB/cBy control Human SCAD deficiency is an inborn error of fatty acid oxidation reported in three infants (1, 2). Two presented with metabolic acidosis and ethylmalonic aciduria and the third presented with severe skeletal muscle weakness, developmental delay, and muscle carnitine deficiency (1, 2). Detailed enzymatic

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confidence: 68%

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confidence: 73%

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Short-Chain Acyl-Coenzyme A Dehydrogenase Activity, Antigen, and Biosynthesis Are Absent in the BALB/cByJ Mouse

et al. 1992

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“…It has been documented previously that some patients have an absence of immunoreactive protein in their cells and that there are mutations that appear to affect folding in a temperature-sensitive manner (41)(42)(43). The mutations either disrupt hydrogen bonding or salt bridge networks and/or disrupt local topology by the introduction of a bulky amino acid side chain, thus affecting monomer folding and oligomer formation.…”

Section: Fig 3 Stereo Diagram Of Acetoacetyl-coa and Amino Acid Resmentioning

confidence: 99%

Crystal Structure of Rat Short Chain Acyl-CoA Dehydrogenase Complexed with Acetoacetyl-CoA

Battaile

Molin-Case

Paschke

et al. 2002

Journal of Biological Chemistry

104

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The acyl-CoA dehydrogenases are a family of flavin adenine dinucleotide-containing enzymes that catalyze the first step in the beta-oxidation of fatty acids and catabolism of some amino acids. They exhibit high sequence identity and yet are quite specific in their substrate binding. Short chain acyl-CoA dehydrogenase has maximal activity toward butyryl-CoA and negligible activity toward substrates longer than octanoyl-CoA. The crystal structure of rat short chain acyl-CoA dehydrogenase complexed with the inhibitor acetoacetyl-CoA has been determined at 2.25 A resolution. Short chain acyl-CoA dehydrogenase is a homotetramer with a subunit mass of 43 kDa and crystallizes in the space group P321 with a = 143.61 A and c = 77.46 A. There are two monomers in the asymmetric unit. The overall structure of short chain acyl-CoA dehydrogenase is very similar to those of medium chain acyl-CoA dehydrogenase, isovaleryl-CoA dehydrogenase, and bacterial short chain acyl-CoA dehydrogenase with a three-domain structure composed of N- and C-terminal alpha-helical domains separated by a beta-sheet domain. Comparison to other acyl-CoA dehydrogenases has provided additional insight into the basis of substrate specificity and the nature of the oxidase activity in this enzyme family. Ten reported pathogenic human mutations and two polymorphisms have been mapped onto the structure of short chain acyl-CoA dehydrogenase. None of the mutations directly affect the binding cavity or intersubunit interactions.

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“…There seem to be two forms : first, a severe infantile systemic form [106,107] ; and secondly, a mild, late-onset phenotype with predominantly muscle involvement [105,108]. The disorder is not expressed in the fibroblasts of patients with the muscle phenotype but is in the infantile variant [109].…”

Section: Scad Deficiencymentioning

confidence: 99%

Mammalian mitochondrial β-oxidation

Eaton

Bartlett

Pourfarzam

1996

Biochemical Journal

382

253

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The enzymic stages of mammalian mitochondrial beta-oxidation were elucidated some 30-40 years ago. However, the discovery of a membrane-associated multifunctional enzyme of beta-oxidation, a membrane-associated acyl-CoA dehydrogenase and characterization of the carnitine palmitoyl transferase system at the protein and at the genetic level has demonstrated that the enzymes of the system itself are incompletely understood. Deficiencies of many of the enzymes have been recognized as important causes of disease. In addition, the study of these disorders has led to a greater understanding of the molecular mechanism of beta-oxidation and the import, processing and assembly of the beta-oxidation enzymes within the mitochondrion. The tissue-specific regulation, intramitochondrial control and supramolecular organization of the pathway is becoming better understood as sensitive analytical and molecular techniques are applied. This review aims to cover enzymological and organizational aspects of mitochondrial beta-oxidation together with the biochemical aspects of inherited disorders of beta-oxidation and the intrinsic control of beta-oxidation.

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Absence of immunoreactive enzyme protewin in short‐chain acylcoenzyme a dehydrogenase deficiency

Cited by 6 publications

References 16 publications

Short-Chain Acyl-Coenzyme A Dehydrogenase Activity, Antigen, and Biosynthesis Are Absent in the BALB/cByJ Mouse

Short-Chain Acyl-Coenzyme A Dehydrogenase Activity, Antigen, and Biosynthesis Are Absent in the BALB/cByJ Mouse

Crystal Structure of Rat Short Chain Acyl-CoA Dehydrogenase Complexed with Acetoacetyl-CoA

Mammalian mitochondrial β-oxidation

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