The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Jerry Vockley - One of the best experts on this subject based on the ideXlab platform.
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Formation of 3-hydroxyglutaric acid in glutaric aciduria type I: in vitro participation of medium chain Acyl-CoA Dehydrogenase.
JIMD reports, 2019Co-Authors: Verena Peters, Jerry Vockley, Sandro Ghisla, Marina Morath, Matthias Mack, Michael Liesert, Wolfgang Buckel, Georg F. Hoffmann, Johannes ZschockeAbstract:3‐Hydroxyglutaric acid (3‐OH‐GA) in urine has been identified as the most reliable diagnostic marker for glutaric aciduria type I (GA I). We showed that hydratation of glutaconyl‐CoA to 3‐hydroxyglutaryl‐CoA, which is subsequently hydrolyzed to 3‐OH‐GA, is efficiently catalyzed by 3‐methylglutaconyl‐CoA hydratase (3‐MGH). We have now investigated whether mitochondrial acyl‐CoA‐Dehydrogenases can convert glutaryl‐CoA to glutaconyl‐CoA. Short‐chain acyl‐CoA Dehydrogenase (SCAD), medium‐chain acyl‐CoA Dehydrogenase (MCAD), and long‐chain acyl‐CoA Dehydrogenase (LCAD) accepted glutaryl‐CoA as a substrate. The highest k cat of glutaryl‐CoA was found for MCAD (0.12 ± 0.01 second−1) and was about 26‐fold and 52‐fold higher than those of LCAD and SCAD, respectively. The turnover of MCAD for glutaryl‐CoA was about 1.5% of that of its natural substrate octanoyl‐CoA. Despite high K m (above 600 μM) and low turnover rate, the oxidation of glutaryl‐CoA by MCAD in combination with 3‐MGH could explain the urinary concentration of 3‐OH‐GA in GA I patients.
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Sirtuin 3 (SIRT3) Protein Regulates Long-chain Acyl-CoA Dehydrogenase by Deacetylating Conserved Lysines Near the Active Site
Journal of Biological Chemistry, 2013Co-Authors: Sivakama S. Bharathi, Yuxun Zhang, Al-walid Mohsen, Radha Uppala, Manimalha Balasubramani, Emanuel M. Schreiber, Guy Uechi, Megan E. Beck, Matthew J. Rardin, Jerry VockleyAbstract:Long-chain Acyl-CoA Dehydrogenase (LCAD) is a key mitochondrial fatty acid oxidation enzyme. We previously demonstrated increased LCAD lysine acetylation in SIRT3 knockout mice concomitant with reduced LCAD activity and reduced fatty acid oxidation. To study the effects of acetylation on LCAD and determine sirtuin 3 (SIRT3) target sites, we chemically acetylated recombinant LCAD. Acetylation impeded substrate binding and reduced catalytic efficiency. Deacetylation with recombinant SIRT3 partially restored activity. Residues Lys-318 and Lys-322 were identified as SIRT3-targeted lysines. Arginine substitutions at Lys-318 and Lys-322 prevented the acetylation-induced activity loss. Lys-318 and Lys-322 flank residues Arg-317 and Phe-320, which are conserved among all Acyl-CoA Dehydrogenases and coordinate the enzyme-bound FAD cofactor in the active site. We propose that acetylation at Lys-318/Lys-322 causes a conformational change which reduces hydride transfer from substrate to FAD. Medium-chain Acyl-CoA Dehydrogenase and Acyl-CoA Dehydrogenase 9, two related enzymes with lysines at positions equivalent to Lys-318/Lys-322, were also efficiently deacetylated by SIRT3 following chemical acetylation. These results suggest that acetylation/deacetylation at Lys-318/Lys-322 is a mode of regulating fatty acid oxidation. The same mechanism may regulate other Acyl-CoA Dehydrogenases.
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Brown adipose tissue function in short-chain Acyl-CoA Dehydrogenase deficient mice.
Biochemical and biophysical research communications, 2010Co-Authors: Helen Skilling, Jerry Vockley, Paul M. Coen, Liane Fairfull, Robert E. Ferrell, Bret H. Goodpaster, Eric S. GoetzmanAbstract:Brown adipose tissue is a highly specialized organ that uses mitochondrial fatty acid oxidation to fuel non-shivering thermogenesis. In mice, mutations in the Acyl-CoA Dehydrogenase family of fatty acid oxidation genes are associated with sensitivity to cold. Brown adipose tissue function has not previously been characterized in these knockout strains. Short-chain Acyl-CoA Dehydrogenase (SCAD) deficient mice were found to have increased brown adipose tissue mass as well as modest cardiac hypertrophy. Uncoupling protein-1 was reduced by 70% in brown adipose tissue and this was not due to a change in mitochondrial number, nor was it due to decreased signal transduction through protein kinase A which is known to be a major regulator of uncoupling protein-1 expression. PKA activity and in vitro lipolysis were normal in brown adipose tissue, although in white adipose tissue a modest increase in basal lipolysis was seen in SCAD-/- mice. Finally, an in vivo norepinephrine challenge of brown adipose tissue thermogenesis revealed normal heat production in SCAD-/- mice. These results suggest that reduced brown adipose tissue function is not the major factor causing cold sensitivity in Acyl-CoA Dehydrogenase knockout strains. We speculate that other mechanisms such as shivering capacity, cardiac function, and reduced hepatic glycogen stores are involved.
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Low expression of long-chain Acyl-CoA Dehydrogenase in human skeletal muscle.
Molecular genetics and metabolism, 2010Co-Authors: Amy C. Maher, Al-walid Mohsen, Jerry Vockley, Mark A. TarnopolskyAbstract:Abstract Purpose: Long-chain Acyl-CoA Dehydrogenase (LCAD) is a mitochondrial flavoenzyme thought to be one of the major enzymes responsible for the first step of long-chain fatty acid (LCFA) β-oxidation. Surprisingly, recent studies have shown LCAD is hardly detectable in human tissues such as liver and heart. Skeletal muscle is the largest organ in the body in terms of mass, and accounts for the majority of LCFA oxidation, especially during exercise. The purpose of this study was to investigate the expression levels of LCAD in human skeletal muscle. Methods: Muscle biopsies were obtained from the vastus lateralis of healthy athletic men and women, and examined for mRNA abundance, protein content, and enzyme activity of LCAD. We compared LCAD content with that of very-long chain Acyl-CoA Dehydrogenase (VLCAD) and medium chain Acyl-CoA Dehydrogenase (MCAD); two mitochondrial β-oxidation enzymes that have overlapping chain-length specificity to that of LCAD. LCAD protein content and enzyme activity were also examined in enriched mitochondrial protein fractions. As controls, LCAD presence in skeletal muscle was compared to human heart, liver, and mouse skeletal muscle. Results: The mRNA presence of LCAD in human skeletal muscle is significantly less than VLCAD and MCAD (0.08±0.01 vs 7.3±0.5 vs 2.4±0.2 respectively, P⩽0.0001). LCAD protein was undetectable in human muscle homogenates, and coordinately LCAD enzyme activity was undetectable in enriched mitochondrial samples. Conclusion: LCAD is minimally expressed in human skeletal muscle and likely does not play a significant role in LCFA oxidation.
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Thermodynamic regulation of human short-chain Acyl-CoA Dehydrogenase by substrate and product binding.
Biochemistry, 2005Co-Authors: Amy K. Saenger, Jerry Vockley, Tien V. Nguyen, Marian T. StankovichAbstract:Human short-chain Acyl-CoA Dehydrogenase (hSCAD) catalyzes the first matrix step in the mitochondrial beta-oxidation cycle for substrates with four and six carbons. Previous studies have shown that the act of substrate/product binding induces a large enzyme potential shift in Acyl-CoA Dehydrogenases. The objective of this work was to examine the thermodynamic regulation of this process through direct characterization of the electrochemical properties of hSCAD using spectroelectrochemical methodology. A large amount of substrate activation was observed in the enzymatic reaction of hSCAD (+33 mV), the greatest magnitude measured in any Acyl-CoA Dehydrogenase to date. To examine the role of the substrate as well as the product in electron transfer by hSCAD, a catalytic base mutation (E368Q) was constructed. The E368Q mutation inactivates the reductive and oxidative pathways such that the individual effects of substrate and product binding on the redox potential can be investigated. Optimal substrate (butyryl-CoA) was seen to shift the flavin redox potential slightly more positive (+38 mV) than did optimal product (crotonyl-CoA) (+31 mV), a finding opposite of that observed in another short-chain enzyme, bacterial SCAD. These results indicate that substrate redox activation occurs in hSCAD leading to a large enzyme midpoint potential shift. Substrate binding in hSCAD appears to make a larger contribution than does product to thermodynamic modulation.
Kay Tanaka - One of the best experts on this subject based on the ideXlab platform.
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Identification of very-long-chain Acyl-CoA Dehydrogenase deficiency in three patients previously diagnosed with long-chain Acyl-CoA Dehydrogenase deficiency.
Pediatric research, 1993Co-Authors: Seiji Yamaguchi, Paul M. Coates, Takashi Hashimoto, Y. Indo, Kay TanakaAbstract:ABSTRACT: Long-chain Acyl-CoA Dehydrogenase (LCAD) deficiency is a disorder of fatty acid β-oxidation. Its diagnosis has been made based on the reduced activity of palmitoyl-CoA dehydrogenation, i.e., in fibroblasts. We previously showed that in immunoblot analysis, an LCAD band of normal size and intensity was detected in fibroblasts from all LCAD-deficient patients tested. In the present study, we amplified via polymerase chain reaction and sequenced LCAD cDNA from three of these LCAD-deficient cell lines, and found perfectly normal LCAD sequences in two of them, indicating that at least these patients were not deficient in LCAD. The third patient was homozygous for an A to C substitution at 997, although it is unknown whether or not 997-C is a normal polymorphism. Although the LCAD sequence data were puzzling, a new enzyme, very-long-chain Acyl-CoA Dehydrogenase (VLCAD), was recently identified. Because VLCAD also has high activity with palmitoyl-CoA as substrate, it was possible that defective VLCAD may cause reduced palmitoyl-CoA dehydrogenating activity. We performed immunoblot analysis of VLCAD in six “LCAD-deficient” patients; VLCAD was negative in three of them, two of whom had a normal LCAD cDNA sequence. These results indicated that a considerable number of the patients who had previously been diagnosed as having LCAD deficiency in fact have VLCAD deficiency.
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Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency
Pediatric Research, 1991Co-Authors: Y. Indo, Paul M. Coates, Daniel E. Hale, Kay TanakaAbstract:ABSTRACT: Long-chain Acyl-CoA Dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepato- and cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain Acyl-CoA Dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain Acyl-CoA Dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency.
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Immunochemical characterization of variant long-chain Acyl-CoA Dehydrogenase in cultured fibroblasts from nine patients with long-chain Acyl-CoA Dehydrogenase deficiency.
Pediatric research, 1991Co-Authors: Y. Indo, Paul M. Coates, Daniel E. Hale, Kay TanakaAbstract:Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency
Arnold W. Strauss - One of the best experts on this subject based on the ideXlab platform.
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Spectrum of medium-chain Acyl-CoA Dehydrogenase deficiency detected by newborn screening.
Pediatrics, 2008Co-Authors: Ho-wen Hsu, Arnold W. Strauss, Thomas H. Zytkovicz, Anne Marie Comeau, Deborah Marsden, Vivian E. Shih, George F. Grady, Roger B. EatonAbstract:OBJECTIVE. Our goal was to describe the clinical spectrum of medium-chain Acyl-CoA Dehydrogenase deficiency detected by routine newborn screening and assess factors associated with elevations of octanoylcarnitine in newborns and characteristics associated with adverse clinical consequences of medium-chain Acyl-CoA Dehydrogenase deficiency. METHODS. The first 47 medium-chain Acyl-CoA Dehydrogenase deficiency cases detected by the New England Newborn Screening Program were classified according to initial and follow-up octanoylcarnitine values, octanoylcarnitine-decanoylcarnitine ratios, medium-chain Acyl-CoA Dehydrogenase genotype, follow-up biochemical parameters, and feeding by breast milk or formula. RESULTS. All 20 patients who were homozygous for 985A→G had high initial octanoylcarnitine values (7.0–36.8 μM) and octanoylcarnitine-decanoylcarnitine ratios (7.0–14.5), whereas the 27 patients with 0 to 1 copy of 985A→G exhibited a wide range of octanoylcarnitine values (0.5–28.6 μM) and octanoylcarnitine-decanoylcarnitine ratios (0.8–12.7). Initial newborn octanoylcarnitine values decreased by days 5 to 8, but the octanoylcarnitine-decanoylcarnitine ratio generally remained stable. Among 985A→G homozygotes, breastfed newborns had higher initial octanoylcarnitine values than newborns who received formula. Adverse events occurred in 5 children, 4 985A→G homozygotes and 1 compound heterozygote with a very high initial octanoylcarnitine: 2 survived severe neonatal hypoglycemia, 1 survived a severe hypoglycemic episode at 15 months of age, and 2 died as a result of medium-chain Acyl-CoA Dehydrogenase deficiency at ages 11 and 33 months. CONCLUSION. Newborn screening for medium-chain Acyl-CoA Dehydrogenase deficiency has detected cases with a wide range of genotypes and biochemical abnormalities. Although most children do well, adverse outcomes have not been entirely avoided. Assessment of potential risk and determination of appropriate treatment remain a challenge.
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Polymorphic ventricular tachycardia and abnormal Ca2+ handling in very-long-chain Acyl-CoA Dehydrogenase null mice.
American journal of physiology. Heart and circulatory physiology, 2007Co-Authors: Andreas A. Werdich, Franz J. Baudenbacher, Igor Dzhura, Loice H. Jeyakumar, J. Kannankeril, Sidney Fleischer, Alison W. Legrone, Dejan Milatovic, Michael Aschner, Arnold W. StraussAbstract:Patients with mutations in the mitochondrial very-long-chain Acyl-CoA Dehydrogenase (VLCAD) gene are at risk for cardiomyopathy, myocardial dysfunction, ventricular tachycardia (VT), and sudden car...
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Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain Acyl-CoA Dehydrogenase
American journal of physiology. Heart and circulatory physiology, 2005Co-Authors: Vernat Exil, Harold F. Sims, Carla D. Gardner, Jeffrey N. Rottman, Beatrijs Bartelds, Zaza Khuchua, Rekha Sindhal, Arnold W. StraussAbstract:Mitochondrial very-long-chain Acyl-CoA Dehydrogenase (VLCAD) deficiency is associated with severe hypoglycemia, cardiac dysfunction, and sudden death in neonates and children. Sudden death is commo...
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A novel mutation of late-onset very-long-chain Acyl-CoA Dehydrogenase deficiency
Pediatric neurology, 2002Co-Authors: Rachel Straussberg, Arnold W. StraussAbstract:We describe a novel mutation in three patients with the myopathic form of very-long-chain Acyl-CoA Dehydrogenase deficiency. Three siblings born to second-degree cousins of Jewish-Iraqi origin exhibited rhabdomyolysis and myoglobinuria as the presenting signs of the mild late-onset form of very-long-chain Acyl-CoA Dehydrogenase deficiency. We screened the patients for mutations in the very-long-chain Acyl-CoA Dehydrogenase gene by amplification of all 20 exons and analysis by single-stranded conformation variance on gel electrophoresis. The patients were homozygous for a novel mutation G637A that alters alanine 173 to threonine. We hypothesize that this missense substitution caused a mild change of enzyme function correlating with the mild clinical features and, thus, favoring a genotype-phenotype correlation.
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Characterization of the Human Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Gene Promoter Region † 746
Pediatric Research, 1998Co-Authors: Zhifang Zhang, Yeging Zhou, Arnold W. StraussAbstract:Characterization of the Human Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Gene Promoter Region † 746
Jung-ja P. Kim - One of the best experts on this subject based on the ideXlab platform.
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Crystal structure of rat short chain Acyl-CoA Dehydrogenase complexed with acetoacetyl-CoA: comparison with other Acyl-CoA Dehydrogenases.
The Journal of biological chemistry, 2002Co-Authors: Kevin P. Battaile, Jerry Vockley, Joann Molin-case, Rosemary Paschke, Ming Wang, Dennis Bennett, Jung-ja P. KimAbstract:The Acyl-CoA Dehydrogenases are a family of flavin adenine dinucleotide-containing enzymes that catalyze the first step in the β-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 α-helical domains separated by a β-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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Medium-long-chain chimeric human Acyl-CoA Dehydrogenase: medium-chain enzyme with the active center base arrangement of long-chain Acyl-CoA Dehydrogenase.
Biochemistry, 1996Co-Authors: Andreas Nandy, Volker Kieweg, Franz-georg Kräutle, Petra Vock, Burkhard Küchler, Peter Bross, Jung-ja P. Kim, Ihab Rasched, Sandro GhislaAbstract:The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate α-hydrogen as H+ is located at position 376 (mature MCADH numbering) on loop JK in medium chain Acyl-CoA Dehydrogenase (MCADH). In long chain Acyl-CoA Dehydrogenase (LCADH) and isovaleryl-CoA Dehydrogenase (IVDH), the corresponding Glu carrying out the same function is placed at position 255 on the adjacent helix G. These glutamates thus act on substrate approaching from two opposite regions at the active center. We have implemented the topology of LCADH in MCADH by carrying out the two mutations Glu376Gly and Thr255Glu. The resulting chimeric enzyme, “medium-/long” chain Acyl-CoA Dehydrogenase (MLCADH) has ∼20% of the activity of MCADH and ∼25% that of LCADH with its best substrates octanoyl-CoA and dodecanoyl-CoA, respectively. MLCADH exhibits an enhanced rate of reoxidation with oxygen, however, with a much narrower substrate chain length specificity that peaks with dodecanoyl-CoA. This is the same maxim...
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Identification of the catalytic base in long chain Acyl-CoA Dehydrogenase.
Biochemistry, 1994Co-Authors: Snezana Djordjevic, Frank E. Frerman, Arnold W. Strauss, Rosemary Paschke, Yu Dong, Jung-ja P. KimAbstract:We have used molecular modeling and site-directed mutagenesis to identify the catalytic residues of human long chain Acyl-CoA Dehydrogenase. Among the Acyl-CoA Dehydrogenases, a family of flavoenzymes involved in beta-oxidation of fatty acids, only the three-dimensional structure of the medium chain fatty acid specific enzyme from pig liver has been determined (Kim, J.-J. P., Wang, M., & Paschke, R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7523-7527). Despite the overall sequence homology, the catalytic residue (E376) of medium chain Acyl-CoA Dehydrogenase is not conserved in isovaleryl- and long chain Acyl-CoA Dehydrogenases. A molecular model of human long chain Acyl-CoA Dehydrogenase was derived using atomic coordinates determined by X-ray diffraction studies of the pig medium chain specific enzyme, interactive graphics, and molecular mechanics calculations. The model suggests that E261 functions as the catalytic base in the long-chain Dehydrogenase. An altered Dehydrogenase in which E261 was replaced by a glutamine was constructed, expressed, purified, and characterized. The mutant enzyme exhibited less than 0.02% of the wild-type activity. These data strongly suggest that E261 is the base that abstracts the alpha-proton of the Acyl-CoA substrate in the catalytic pathway of this Dehydrogenase.
Y. Indo - One of the best experts on this subject based on the ideXlab platform.
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Identification of very-long-chain Acyl-CoA Dehydrogenase deficiency in three patients previously diagnosed with long-chain Acyl-CoA Dehydrogenase deficiency.
Pediatric research, 1993Co-Authors: Seiji Yamaguchi, Paul M. Coates, Takashi Hashimoto, Y. Indo, Kay TanakaAbstract:ABSTRACT: Long-chain Acyl-CoA Dehydrogenase (LCAD) deficiency is a disorder of fatty acid β-oxidation. Its diagnosis has been made based on the reduced activity of palmitoyl-CoA dehydrogenation, i.e., in fibroblasts. We previously showed that in immunoblot analysis, an LCAD band of normal size and intensity was detected in fibroblasts from all LCAD-deficient patients tested. In the present study, we amplified via polymerase chain reaction and sequenced LCAD cDNA from three of these LCAD-deficient cell lines, and found perfectly normal LCAD sequences in two of them, indicating that at least these patients were not deficient in LCAD. The third patient was homozygous for an A to C substitution at 997, although it is unknown whether or not 997-C is a normal polymorphism. Although the LCAD sequence data were puzzling, a new enzyme, very-long-chain Acyl-CoA Dehydrogenase (VLCAD), was recently identified. Because VLCAD also has high activity with palmitoyl-CoA as substrate, it was possible that defective VLCAD may cause reduced palmitoyl-CoA dehydrogenating activity. We performed immunoblot analysis of VLCAD in six “LCAD-deficient” patients; VLCAD was negative in three of them, two of whom had a normal LCAD cDNA sequence. These results indicated that a considerable number of the patients who had previously been diagnosed as having LCAD deficiency in fact have VLCAD deficiency.
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Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency
Pediatric Research, 1991Co-Authors: Y. Indo, Paul M. Coates, Daniel E. Hale, Kay TanakaAbstract:ABSTRACT: Long-chain Acyl-CoA Dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepato- and cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain Acyl-CoA Dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain Acyl-CoA Dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency.
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Immunochemical characterization of variant long-chain Acyl-CoA Dehydrogenase in cultured fibroblasts from nine patients with long-chain Acyl-CoA Dehydrogenase deficiency.
Pediatric research, 1991Co-Authors: Y. Indo, Paul M. Coates, Daniel E. Hale, Kay TanakaAbstract:Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency
