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39 results on '"Acyl-CoA Dehydrogenases"'

1. Structural basis for expanded substrate specificities of human long chain acyl-CoA dehydrogenase and related acyl-CoA dehydrogenases

Author

Narayanan, Beena, Xia, Chuanwu, McAndrew, Ryan, Shen, Anna L, and Kim, Jung-Ja P

Subjects
Biochemistry and Cell Biology, Biological Sciences, Substrate Specificity, Humans, Acyl-CoA Dehydrogenase, Long-Chain, Models, Molecular, Crystallography, X-Ray, Catalytic Domain, Acyl-CoA Dehydrogenases, Protein Conformation, Amino Acid Sequence
Abstract

Crystal structures of human long-chain acyl-CoA dehydrogenase (LCAD) and the catalytically inactive Glu291Gln mutant, have been determined. These structures suggest that LCAD harbors functions beyond its historically defined role in mitochondrial β-oxidation of long and medium-chain fatty acids. LCAD is a homotetramer containing one FAD per 43 kDa subunit with Glu291 as the catalytic base. The substrate binding cavity of LCAD reveals key differences which makes it specific for longer and branched chain substrates. The presence of Pro132 near the start of the E helix leads to helix unwinding that, together with adjacent smaller residues, permits binding of bulky substrates such as 3α, 7α, l2α-trihydroxy-5β-cholestan-26-oyl-CoA. This structural element is also utilized by ACAD11, a eucaryotic ACAD of unknown function, as well as bacterial ACADs known to metabolize sterol substrates. Sequence comparison suggests that ACAD10, another ACAD of unknown function, may also share this substrate specificity. These results suggest that LCAD, ACAD10, ACAD11 constitute a distinct class of eucaryotic acyl CoA dehydrogenases.

Published
2024

2. Treatment of VLCAD-Deficient Patient Fibroblasts with Peroxisome Proliferator-Activated Receptor δ Agonist Improves Cellular Bioenergetics.

Author

D'Annibale, Olivia M., Phua, Yu Leng, Van't Land, Clinton, Karunanidhi, Anuradha, Dorenbaum, Alejandro, Mohsen, Al-Walid, and Vockley, Jerry

Subjects
*PEROXISOME proliferator-activated receptors, *BIOENERGETICS, *ADOLESCENCE, *FIBROBLASTS, *GENE expression, *MISSENSE mutation
Abstract

Background: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive disease that prevents the body from utilizing long-chain fatty acids for energy, most needed during stress and fasting. Symptoms can appear from infancy through childhood and adolescence or early adulthood, and include hypoglycemia, recurrent rhabdomyolysis, myopathy, hepatopathy, and cardiomyopathy. REN001 is a peroxisome-proliferator-activated receptor delta (PPARδ) agonist that modulates the expression of the genes coding for fatty acid β-oxidation enzymes and proteins involved in oxidative phosphorylation. Here, we assessed the effect of REN001 on VLCAD-deficient patient fibroblasts. Methods: VLCAD-deficient patient and control fibroblasts were treated with REN001. Cells were harvested for gene expression analysis, protein content, VLCAD enzyme activity, cellular bioenergetics, and ATP production. Results: VLCAD-deficient cell lines responded differently to REN001 based on genotype. All cells had statistically significant increases in ACADVL gene expression. Small increases in VLCAD protein and enzyme activity were observed and were cell-line- and dose-dependent. Even with these small increases, cellular bioenergetics improved in all cell lines in the presence of REN001, as demonstrated by the oxygen consumption rate and ATP production. VLCAD-deficient cell lines containing missense mutations responded better to REN001 treatment than one containing a duplication mutation in ACADVL. Discussion: Treating VLCAD-deficient fibroblasts with the REN001 PPARδ agonist results in an increase in VLCAD protein and enzyme activity, and a decrease in cellular stress. These results establish REN001 as a potential therapy for VLCADD as enhanced expression may provide a therapeutic increase in total VLCAD activity, but suggest the need for mutation-specific treatment augmented by other treatment measures. [ABSTRACT FROM AUTHOR]

Published
2022
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3. Data on Flavoproteins Discussed by Researchers at American University of Beirut Medical Center (Diagnostic challenges and outcome of fatty acid oxidation defects in a tertiary care center in Lebanon).

Abstract

A report from the American University of Beirut Medical Center discusses the diagnostic challenges and outcomes of fatty acid oxidation defects in Lebanon. Fatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations. The study found that most families with these defects were consanguineous (first-degree cousins) and that the majority of patients were diagnosed when clinically symptomatic. The most common defect identified was carnitine transporter deficiency, and the overall survival rate was 75% with treatment. The researchers emphasize the importance of physician awareness and systematic neonatal screening for early detection and improved outcomes. [Extracted from the article]

Published
2024

4. Researchers at Manchester University NHS Foundation Trust Report New Data on Ketogenic Diet (Long-term Use of Investigational B-hydroxybutyrate Salts In Children With Multiple Acyl-coa Dehydrogenase or Pyruvate Dehydrogenase Deficiency).

Subjects
KETOGENIC diet, ACYL coenzyme A, RESEARCH personnel, SALTS, PYRUVATES, GLUCOSE-6-phosphate dehydrogenase deficiency
Abstract

The article focuses on evaluating the long-term effects of a new formulation of beta-hydroxybutyrate salts in children with metabolic disorders, specifically multiple acyl-CoA dehydrogenase deficiency (MADD) and pyruvate dehydrogenase deficiency. Topics include the improvement in palatability and treatment outcomes with the new formulation, the correction of hypernatraemia in MADD patients, and the enhancement of ketosis in a PDH deficiency case.

Published
2024

5. Treatment of VLCAD-Deficient Patient Fibroblasts with Peroxisome Proliferator-Activated Receptor δ Agonist Improves Cellular Bioenergetics

Author

Olivia M. D’Annibale, Yu Leng Phua, Clinton Van’t Land, Anuradha Karunanidhi, Alejandro Dorenbaum, Al-Walid Mohsen, and Jerry Vockley

Subjects
fatty acid oxidation, VLCAD deficiency, ACADs, PPARs, acyl-CoA dehydrogenases, REN001, Cytology, QH573-671
Abstract

Background: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive disease that prevents the body from utilizing long-chain fatty acids for energy, most needed during stress and fasting. Symptoms can appear from infancy through childhood and adolescence or early adulthood, and include hypoglycemia, recurrent rhabdomyolysis, myopathy, hepatopathy, and cardiomyopathy. REN001 is a peroxisome-proliferator-activated receptor delta (PPARδ) agonist that modulates the expression of the genes coding for fatty acid β-oxidation enzymes and proteins involved in oxidative phosphorylation. Here, we assessed the effect of REN001 on VLCAD-deficient patient fibroblasts. Methods: VLCAD-deficient patient and control fibroblasts were treated with REN001. Cells were harvested for gene expression analysis, protein content, VLCAD enzyme activity, cellular bioenergetics, and ATP production. Results: VLCAD-deficient cell lines responded differently to REN001 based on genotype. All cells had statistically significant increases in ACADVL gene expression. Small increases in VLCAD protein and enzyme activity were observed and were cell-line- and dose-dependent. Even with these small increases, cellular bioenergetics improved in all cell lines in the presence of REN001, as demonstrated by the oxygen consumption rate and ATP production. VLCAD-deficient cell lines containing missense mutations responded better to REN001 treatment than one containing a duplication mutation in ACADVL. Discussion: Treating VLCAD-deficient fibroblasts with the REN001 PPARδ agonist results in an increase in VLCAD protein and enzyme activity, and a decrease in cellular stress. These results establish REN001 as a potential therapy for VLCADD as enhanced expression may provide a therapeutic increase in total VLCAD activity, but suggest the need for mutation-specific treatment augmented by other treatment measures.

Published
2022
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7. Patent Issued for Use of PPAR-delta agonists in the treatment of disease (USPTO 11931365).

Subjects
THERAPEUTICS, CARNITINE palmitoyltransferase, PATENTS, GLYCOGEN storage disease, MITOCHONDRIAL DNA
Abstract

Reneo Pharmaceuticals Inc. has been issued a patent for the use of PPAR-delta agonists in the treatment of various diseases and disorders. The patent describes a method for treating conditions such as muscle atrophy, mitochondrial myopathy, fatty acid oxidation disorders, kidney disease, glycogen storage disease, and more. The inventors claim that the administration of a specific compound, sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate, can improve exercise tolerance, muscle histology, cognition, overall well-being, and reduce pain and fatigue in patients with these conditions. The patent provides detailed information on the dosage and administration of the compound. [Extracted from the article]

Published
2024

8. Tohoku University School of Medicine Researchers Report Recent Findings in Type 2 Diabetes (Stealthy progression of type 2 diabetes mellitus due to impaired ketone production in an adult patient with multiple acyl-CoA dehydrogenase deficiency).

Abstract

Researchers from Tohoku University School of Medicine in Japan have published a report on the stealthy progression of type 2 diabetes in a patient with multiple acyl-CoA dehydrogenase deficiency (MADD). MADD is an inherited metabolic disorder that impairs fatty acid oxidation and ketone body production. The patient, a 32-year-old man, had been on a high-carbohydrate diet for over 30 years and exhibited symptoms resembling diabetic ketoacidosis. This case highlights the potential association between long-term adherence to a high-carbohydrate diet and the development of type 2 diabetes. Further research is needed to understand the long-term complications associated with this diet and the progression of diabetes in patients with MADD. [Extracted from the article]

Published
2024

9. Research Reports on Adenovirus from Guangdong Pharmaceutical University Provide New Insights (Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis).

Abstract

A recent study from Guangdong Pharmaceutical University in China has investigated the role of Short-Chain Acyl-CoA Dehydrogenase (SCAD) in cardiac fibrosis, a condition associated with heart failure. The researchers conducted in-vivo and in-vitro experiments using hypertensive rats, SCAD knockout mice, and cardiac fibroblasts. They found that SCAD expression was significantly decreased in hypertensive rats and in cardiac fibroblasts treated with angiotensin II. Swim training was shown to ameliorate cardiac fibrosis in hypertensive rats by increasing SCAD levels. The study suggests that SCAD may be a potential therapeutic target for suppressing cardiac fibrosis. [Extracted from the article]

Published
2024

10. University of Aveiro Reports Findings in Flavoproteins (Plasma lipidomics analysis reveals altered profile of triglycerides and phospholipids in children with Medium-Chain Acyl-CoA dehydrogenase deficiency).

Subjects
FLAVOPROTEINS, ACYL coenzyme A, LIPIDOMICS, PHOSPHOLIPIDS, TRIGLYCERIDES
Abstract

A recent study conducted by researchers at the University of Aveiro in Portugal examined the lipid profile of children with Medium-Chain Acyl-CoA dehydrogenase deficiency (MCADD), a common mitochondrial fatty acid b-oxidation disorder. The study analyzed plasma samples from 25 children with MCADD and 21 pediatric control subjects. The researchers found significant differences in lipid species between the two groups, particularly in triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids. These findings suggest an underlying alteration in lipid metabolism in children with MCADD, and further research is needed to understand the long-term impacts of these changes. [Extracted from the article]

Published
2024

11. Bioconversion of Phytosterols to 9-Hydroxy-3-Oxo-4,17-Pregadiene-20-Carboxylic Acid Methyl Ester by Enoyl-CoA Deficiency and Modifying Multiple Genes in Mycolicibacterium neoaurum

Author

Chenyang Yuan, Shikui Song, Jianxin He, Jingxian Zhang, Xiangcen Liu, Eliana L. Pena, Junsong Sun, Jiping Shi, Zhengding Su, and Baoguo Zhang

Subjects
Ecology, Carboxylic Acids, Phytosterols, Esters, Ketosteroids, Applied Microbiology and Biotechnology, Acyl-CoA Dehydrogenases, Prodrugs, Steroids, Acyl Coenzyme A, Oxidoreductases, Enoyl-CoA Hydratase, Food Science, Biotechnology
Abstract

Steroid drug precursors, including C19 and C22 steroids, are crucial to steroid drug synthesis and development. However, C22 steroids are less developed due to the intricacy of the steroid metabolic pathway. In this study, a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), was successfully obtained from Mycolicibacterium neoaurum by 3-ketosteroid-Δ(1)-dehydrogenase and enoyl-CoA hydratase ChsH deficiency. The production of 9-OH-PDCE was improved by the overexpression of 17β-hydroxysteroid dehydrogenase Hsd4A and acyl-CoA dehydrogenase ChsE1-ChsE2 to reduce the accumulation of by-products. The purity of 9-OH-PDCE in fermentation broth was improved from 71.7% to 89.7%. Hence, the molar yield of 9-OH-PDCE was improved from 66.7% to 86.7%, with a yield of 0.78 g/L. Furthermore, enoyl-CoA hydratase ChsH1-ChsH2 was identified to form an indispensable complex in Mycolicibacterium neoaurum DSM 44704. IMPORTANCE C22 steroids are valuable precursors for steroid drug synthesis, but the development of C22 steroids remains unsatisfactory. This study presented a strategy for the one-step bioconversion of phytosterols to a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), by 3-ketosteroid-Δ(1)-dehydrogenase and enoyl-CoA hydratase deficiency with overexpression of 17β-hydroxysteroid dehydrogenase acyl-CoA dehydrogenase in Mycolicibacterium. The function of the enoyl-CoA hydratase ChsH in vivo was revealed. Construction of the novel C22 steroid drug precursor producer provided more potential for steroid drug synthesis, and the characterization of the function of ChsH and the transformation of steroids further revealed the steroid metabolic pathway.

Published
2023

13. Researchers from Monash University Report Findings in Gene Therapy [A Gene Therapy Targeting Medium-chain Acyl-coa Dehydrogenase (Mcad) Did Not Protect Against Diabetes-induced Cardiac Pathology].

Abstract

Researchers from Monash University in Clayton, Australia have conducted a study on gene therapy for diabetic cardiomyopathy, a heart disease that affects patients with diabetes. The researchers aimed to determine if increasing the expression of a specific enzyme called medium-chain acyl-coenzyme A dehydrogenase (MCAD) could improve the function of the diabetic heart. However, their findings showed that the gene therapy targeting MCAD did not significantly improve diabetes-induced cardiac pathology or metabolic markers. The researchers also noted that the uptake of the viral vectors used in the therapy was reduced in the diabetic heart, which may have implications for future clinical translation. [Extracted from the article]

Published
2023

14. Researchers from Tulane University Describe Findings in Flavoproteins (Biochemical and Molecular Characteristics Among Infants With Abnormal Newborn Screen for Very-long-chain Acyl-coa Dehydrogenase Deficiency: a Single Center Experience).

Subjects
NEWBORN infants, FLAVOPROTEINS, NEWBORN screening, ACYL coenzyme A, RESEARCH personnel
Abstract

A recent report from Tulane University discusses the biochemical and molecular characteristics of infants with abnormal newborn screens for very-long-chain acyl-coa dehydrogenase deficiency (VLCAD). The study analyzed the acylcarnitine profiles and enzyme analysis of a large cohort of VLCAD positive cases detected through newborn screening. The researchers found that the elevation of the C14:1/C12:1 ratio in both dried blood spot and plasma acylcarnitine profiles was informative in distinguishing affected individuals from unaffected ones. This research contributes to improving the accuracy of confirmatory testing for infants with presumptive positive VLCAD deficiency. [Extracted from the article]

Published
2023

15. An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system

Author

Matthew Eskell and Hashim Khan

Subjects
Iron-Sulfur Proteins, Oxidoreductases Acting on CH-NH Group Donors, Acyl-CoA Dehydrogenases, Electron-Transferring Flavoproteins, Mutation, Humans, Female, General Medicine, Middle Aged, Multiple Acyl Coenzyme A Dehydrogenase Deficiency, Education
Abstract

Multiple-acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder which can be split into three types. Type III MADD is associated with acute or subacute proximal muscle weakness and other variable non-specific features making it a challenging diagnosis for the clinician. This case report describes MADD in a 64 year-old lady, thought to be one of the latest first presentations of the disease. Unusually for this condition, the initial presentation was with dyspnoea. Furthermore, since this case provides further evidence that gene variants can predict age of onset, we advocate for further subclassification of type III MADD into late onset MADD (LO-MADD) when homozygous gene variants are present and very LO-MADD when heterozygous gene variants are found.

Published
2022

16. Dynamics of acylcarnitines, hypoglycin A, méthylènecyclopropylglycine and their metabolites in a Kladruber stallion with atypical myopathy

Author

Petr Jahn, Dana Dobešová, Radana Brumarová, Katarína Tóthová, Andrea Kopecká, and David Friedecký

Subjects
Cyclopropanes, Hypoglycins, Male, General Veterinary, Acyl-CoA Dehydrogenases, Muscular Diseases, Carnitine, Fatty Acids, Glycine, Animals, Horse Diseases, Horses, Creatine Kinase
Abstract

Equine atypical myopathy (AM also referred to as multiple acyl-CoA dehydrogenases deficiency [MADD]) is thought to be caused by toxins metabolized from hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG). HGA is contained in the seeds and seedlings of the sycamore tree (

Published
2022

17. Research Data from Marshall University Update Understanding of Steatosis (Under Peroxisome Proliferation Acyl-coa Oxidase Coordinates With Catalase To Enhance Ethanol Metabolism).

Abstract

Keywords: Huntington; State:West Virginia; United States; North and Central America; Acyl-CoA Dehydrogenases; Acyl-CoA Oxidase; Alcohols; Catalase; Enzymes and Coenzymes; Enzymology; Ethanol; Ethanolamines; Flavoproteins; Health and Medicine; Oxidase; Oxidoreductases; Peroxidases; Proteins; Steatosis EN Huntington State:West Virginia United States North and Central America Acyl-CoA Dehydrogenases Acyl-CoA Oxidase Alcohols Catalase Enzymes and Coenzymes Enzymology Ethanol Ethanolamines Flavoproteins Health and Medicine Oxidase Oxidoreductases Peroxidases Proteins Steatosis 5228 5228 1 11/06/23 20231110 NES 231110 2023 NOV 10 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Week -- Fresh data on Steatosis are presented in a new report. For more information on this research see: Under Peroxisome Proliferation Acyl-coa Oxidase Coordinates With Catalase To Enhance Ethanol Metabolism. [Extracted from the article]

Published
2023

18. Findings from University of Pittsburgh Has Provided New Data on Oxidoreductases Acting on CH-CH Group Donors (Heptanoic and Medium Branched-chain Fatty Acids As Anaplerotic Treatment for Medium Chain Acyl-coa Dehydrogenase Deficiency).

Abstract

Keywords: Pittsburgh; State:Pennsylvania; United States; North and Central America; Acyl-CoA Dehydrogenases; Dehydrogenase; Enzymes and Coenzymes; Flavoproteins; Genetics; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Proteins EN Pittsburgh State:Pennsylvania United States North and Central America Acyl-CoA Dehydrogenases Dehydrogenase Enzymes and Coenzymes Flavoproteins Genetics Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Proteins 1094 1094 1 11/06/23 20231110 NES 231110 2023 NOV 10 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Data detailed on Enzymes and Coenzymes - Oxidoreductases Acting on CH-CH Group Donors have been presented. Keywords for this news article include: Pittsburgh, Pennsylvania, United States, North and Central America, Acyl-CoA Dehydrogenases, Dehydrogenase, Enzymes and Coenzymes, Flavoproteins, Genetics, Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Proteins, University of Pittsburgh. [Extracted from the article]

Published
2023

19. Division of Gastroenterology Researcher Updates Knowledge of Hepatomegaly (Multiple Acyl-CoA Dehydrogenase Deficiency: A Rare Cause of Hepatomegaly).

Subjects
ACYL coenzyme A, HEPATOMEGALY, RESEARCH personnel, GASTROENTEROLOGY, DIGESTIVE system diseases, LIVER enzymes
Abstract

For more information on this research see: Multiple Acyl-CoA Dehydrogenase Deficiency: A Rare Cause of Hepatomegaly. Keywords: Acyl-CoA Dehydrogenases; Dehydrogenase; Digestive System Diseases and Conditions; Enzymes and Coenzymes; Gastroenterology; Health and Medicine; Hepatomegaly; Liver Diseases and Conditions; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors EN Acyl-CoA Dehydrogenases Dehydrogenase Digestive System Diseases and Conditions Enzymes and Coenzymes Gastroenterology Health and Medicine Hepatomegaly Liver Diseases and Conditions Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors 207 207 1 10/30/23 20231031 NES 231031 2023 OCT 30 (NewsRx) -- By a News Reporter-Staff News Editor at Gastroenterology Week -- Research findings on hepatomegaly are discussed in a new report. [Extracted from the article]

Published
2023

20. Children's Hospital Researcher Describes Recent Advances in Flavoproteins (Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency: Family Impact and Perspectives).

Subjects
FLAVOPROTEINS, CHILDREN'S hospitals, ACYL coenzyme A, RESEARCH personnel
Abstract

Keywords: Acyl-CoA Dehydrogenases; Dehydrogenase; Enzymes and Coenzymes; Flavoproteins; Long-Chain Acyl-CoA Dehydrogenase; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Proteins EN Acyl-CoA Dehydrogenases Dehydrogenase Enzymes and Coenzymes Flavoproteins Long-Chain Acyl-CoA Dehydrogenase Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Proteins 144 144 1 10/24/23 20231023 NES 231023 2023 OCT 23 (NewsRx) -- By a News Reporter-Staff News Editor at Cardiovascular Week -- Research findings on flavoproteins are discussed in a new report. Acyl-CoA Dehydrogenases, Dehydrogenase, Enzymes and Coenzymes, Flavoproteins, Long-Chain Acyl-CoA Dehydrogenase, Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Proteins. [Extracted from the article]

Published
2023

21. Reports Outline Osteoporosis Study Results from Chung Shan Medical University (A Case Report On Multiple Acyl-coa Dehydrogenase Deficiency With Severe Myopathy and Osteoporosis).

Abstract

Keywords: Taichung; Taiwan; Asia; Acyl-CoA Dehydrogenases; Bone Research; Dehydrogenase; Enzymes and Coenzymes; Flavoproteins; Health and Medicine; Metabolic Bone Diseases and Conditions; Musculoskeletal Diseases and Conditions; Myopathy; Osteoporosis; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Proteins EN Taichung Taiwan Asia Acyl-CoA Dehydrogenases Bone Research Dehydrogenase Enzymes and Coenzymes Flavoproteins Health and Medicine Metabolic Bone Diseases and Conditions Musculoskeletal Diseases and Conditions Myopathy Osteoporosis Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Proteins 1191 1191 1 10/16/23 20231020 NES 231020 2023 OCT 20 (NewsRx) -- By a News Reporter-Staff News Editor at Pain & Central Nervous System Week -- Researchers detail new data in Musculoskeletal Diseases and Conditions - Osteoporosis. For more information on this research see: A Case Report On Multiple Acyl-coa Dehydrogenase Deficiency With Severe Myopathy and Osteoporosis. [Extracted from the article]

Published
2023

22. University Clinical Center of Kosovo Researchers Describe Advances in Epileptic Encephalopathy (Case report: Diagnosis of a patient with Sifrim-Hitz-Weiss syndrome, development and epileptic encephalopathy-14, and medium chain acyl-CoA...).

Abstract

Acyl-CoA Dehydrogenases, Brain Diseases and Conditions, Central Nervous System Diseases and Conditions, Dehydrogenase, Diagnostics and Screening, Drugs and Therapies, Enzymes and Coenzymes, Epilepsy, Epileptic Encephalopathy, Genetics, Health and Medicine, Nervous System Diseases and Conditions, Neurologic Manifestations, Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Proteins, Seizures, Flavoproteins Keywords: Acyl-CoA Dehydrogenases; Brain Diseases and Conditions; Central Nervous System Diseases and Conditions; Dehydrogenase; Diagnostics and Screening; Drugs and Therapies; Enzymes and Coenzymes; Epilepsy; Epileptic Encephalopathy; Flavoproteins; Genetics; Health and Medicine; Nervous System Diseases and Conditions; Neurologic Manifestations; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Proteins; Seizures EN Acyl-CoA Dehydrogenases Brain Diseases and Conditions Central Nervous System Diseases and Conditions Dehydrogenase Diagnostics and Screening Drugs and Therapies Enzymes and Coenzymes Epilepsy Epileptic Encephalopathy Flavoproteins Genetics Health and Medicine Nervous System Diseases and Conditions Neurologic Manifestations Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Proteins Seizures 2541 2541 1 09/19/23 20230922 NES 230922 2023 SEP 22 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- A new study on epileptic encephalopathy is now available. For more information on this research see: Case report: Diagnosis of a patient with Sifrim-Hitz-Weiss syndrome, development and epileptic encephalopathy-14, and medium chain acyl-CoA dehydrogenase deficiency. [Extracted from the article]

Published
2023

23. Study Results from Guangdong Pharmaceutical University Update Understanding of Apoptosis (Short-chain Acyl-coa Dehydrogenase Is a Potential Target for the Treatment of Vascular Remodelling).

Abstract

SCAD siRNA caused HUVEC apoptosis in vitro, whereas adenovirus-mediated SCAD overexpression (Ad-SCAD) protected against HUVEC apoptosis. Keywords: Guangzhou; People's Republic of China; Asia; Acyl-CoA Dehydrogenases; Apoptosis; Cellular Physiology; Dehydrogenase; Drugs and Therapies; Enzymes and Coenzymes; Flavoproteins; Health and Medicine; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Pharmaceuticals; Proteins EN Guangzhou People's Republic of China Asia Acyl-CoA Dehydrogenases Apoptosis Cellular Physiology Dehydrogenase Drugs and Therapies Enzymes and Coenzymes Flavoproteins Health and Medicine Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Pharmaceuticals Proteins 2441 2441 1 09/19/23 20230918 NES 230918 2023 SEP 22 (NewsRx) -- By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Investigators publish new report on Cellular Physiology - Apoptosis. [Extracted from the article]

Published
2023

24. Identification of Differential Expression Genes between Volume and Pressure Overloaded Hearts Based on Bioinformatics Analysis

Author

Yuanfeng Fu, Di Zhao, Yufei Zhou, Jing Lu, Le Kang, Xueli Jiang, Ran Xu, Zhiwen Ding, and Yunzeng Zou

Subjects
Mice, Acyl-CoA Dehydrogenases, Gene Expression Profiling, Fatty Acids, Genetics, Animals, Computational Biology, PPAR alpha, volume overload, microarray datasets, deferentially expressed genes, biomarkers, bioinformatics analysis, Genetics (clinical), Biomarkers
Abstract

Volume overload (VO) and pressure overload (PO) are two common pathophysiological conditions associated with cardiac disease. VO, in particular, often occurs in a number of diseases, and no clinically meaningful molecular marker has yet been established. We intend to find the main differential gene expression using bioinformatics analysis. GSE97363 and GSE52796 are the two gene expression array datasets related with VO and PO, respectively. The LIMMA algorithm was used to identify differentially expressed genes (DEGs) of VO and PO. The DEGs were divided into three groups and subjected to functional enrichment analysis, which comprised GO analysis, KEGG analysis, and the protein–protein interaction (PPI) network. To validate the sequencing data, cardiomyocytes from AR and TAC mouse models were used to extract RNA for qRT-PCR. The three genes with random absolute values of LogFC and indicators of heart failure (natriuretic peptide B, NPPB) were detected: carboxylesterase 1D (CES1D), whirlin (WHRN), and WNK lysine deficient protein kinase 2 (WNK2). The DEGs in VO and PO were determined to be 2761 and 1093, respectively, in this study. Following the intersection, 305 genes were obtained, 255 of which expressed the opposing regulation and 50 of which expressed the same regulation. According to the GO and pathway enrichment studies, DEGs with opposing regulation are mostly common in fatty acid degradation, propanoate metabolism, and other signaling pathways. Finally, we used Cytoscape’s three techniques to identify six hub genes by intersecting 255 with the opposite expression and constructing a PPI network. Peroxisome proliferator-activated receptor (PPARα), acyl-CoA dehydrogenase medium chain (ACADM), patatin-like phospholipase domain containing 2 (PNPLA2), isocitrate dehydrogenase 3 (IDH3), heat shock protein family D member 1 (HSPD1), and dihydrolipoamide S-acetyltransferase (DLAT) were identified as six potential genes. Furthermore, we predict that the hub genes PPARα, ACADM, and PNPLA2 regulate VO myocardial changes via fatty acid metabolism and acyl-Coa dehydrogenase activity, and that these genes could be employed as basic biomarkers for VO diagnosis and treatment.

Published
2022
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25. Hepatocellular carcinoma stage: an almost loss of fatty acid metabolism and gain of glucose metabolic pathways dysregulation

Author

Karthik Balakrishnan

Subjects
Cancer Research, Carcinoma, Hepatocellular, Carcinogenesis, Glutamine, Fatty Acids, Liver Neoplasms, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Hematology, General Medicine, Phosphoglycerate Kinase, Glucose, Oncology, Acyl-CoA Dehydrogenases, Humans, Oxidoreductases, Pyruvates, Metabolic Networks and Pathways, Acetyl-CoA Carboxylase
Abstract

Cancer cells rewire the metabolic processes beneficial for cancer cell proliferation, survival, and their progression. In this study, metabolic processes related to glucose, glutamine, and fatty acid metabolism signatures were collected from the molecular signatures database and investigated in the context of energy metabolic pathways through available genome-wide expression profiles of liver cancer cohorts by gene sets-based pathway activation scoring analysis. The outcomes of this study portray that the fatty acid metabolism, transport, and its storage related signatures are highly expressed across early stages of liver tumors and on the contrary, the gene sets related to glucose transport and glucose metabolism are prominently activated in the hepatocellular carcinoma (HCC) stage. Based on the results, these metabolic pathways are clearly dysregulated across specific stages of carcinogenesis. The identified dimorphic metabolic pathway dysregulation patterns are further reconfirmed by examining corresponding metabolic pathway genes expression patterns across various stages encompassing profiles. Recurrence is the primary concern in the carcinogenesis of liver tumors due to liver tissues regeneration. Hence, to further explore these dysregulation effects on recurrent cirrhosis and recurrent HCC sample containing profile GSE20140 was examined and interestingly, this result also reiterated these differential metabolic pathways dysregulation. In addition, a recently established metabolome profile for the massive panel of cancer cell-lines, including liver cancer cell-lines, was used for further exploration. These findings also reassured those differential metabolites abundance of the fatty acid and glucose metabolic pathways enlighten those dimorphic metabolic pathways dysregulation. Moreover, ROC curves of fatty acid metabolic pathway genes such as acetyl-CoA carboxylase (ACACB), acyl-CoA dehydrogenase long chain (ACADL), and acyl-CoA dehydrogenase medium chain (ACADM) as well as glucose metabolic pathway genes such as phosphoglycerate kinase (PGK1), pyruvate dehydrogenase (PDHA1), pyruvate dehydrogenase kinase (PDK1) demonstrated greater sensitivity and specificity in the corresponding stage-specific tumors with significant p-values (p 0.05). Furthermore, overall survival (OS) and recurrence-free survival (RFS) studies also reconfirmed that the rate-limiting genes expression of fatty acid and glucose metabolic pathways reveal better and poor survival in HCC patient cohorts, respectively. In conclusion, all these results clearly show that metabolic rewiring and the existence of two diverse metabolic pathways dysregulation involving fatty acid and glucose metabolism across the stages of liver tumors have been identified. These findings might be useful for developing therapeutic target treatments in stage-specific tumors.

Published
2022

26. Messenger RNA rescues medium-chain acyl-CoA dehydrogenase deficiency in fibroblasts from patients and a murine model.

Author

Zhao XJ, Mohsen AW, Mihalik S, Solo K, Basu S, Aliu E, Shi H, Kochersberger C, Karunanidhi A, Van't Land C, Coughlan KA, Siddiqui S, Rice LM, Hillier S, Guadagnin E, DeAntonis C, Giangrande PH, Martini PGV, and Vockley J

Subjects
Humans, Mice, Animals, Acyl-CoA Dehydrogenase genetics, Acyl-CoA Dehydrogenase metabolism, RNA, Messenger genetics, Disease Models, Animal, Fibroblasts metabolism, Acyl-CoA Dehydrogenases
Abstract

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid β-oxidation (FAO) in humans. Patients exhibit clinical episodes often associated with fasting. Symptoms include hypoketotic hypoglycemia and Reye-like episodes. With limited treatment options, we explored the use of human MCAD (hMCAD) mRNA in fibroblasts from patients with MCAD deficiency to provide functional MCAD protein and reverse the metabolic block. Transfection of hMCAD mRNA into MCAD- deficient patient cells resulted in an increased MCAD protein that localized to mitochondria, concomitant with increased enzyme activity in cell extracts. The therapeutic hMCAD mRNA-lipid nanoparticle (LNP) formulation was also tested in vivo in Acadm-/- mice. Administration of multiple intravenous doses of the hMCAD mRNA-LNP complex (LNP-MCAD) into Acadm-/- mice produced a significant level of MCAD protein with increased enzyme activity in liver, heart and skeletal muscle homogenates. Treated Acadm-/- mice were more resistant to cold stress and had decreased plasma levels of medium-chain acylcarnitines compared to untreated animals. Furthermore, hepatic steatosis in the liver from treated Acadm-/- mice was reduced compared to untreated ones. Results from this study support the potential therapeutic value of hMCAD mRNA-LNP complex treatment for MCAD deficiency., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2023
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27. Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism ( FBP1, ACAD9) and vesicle trafficking (RAB27A) .

Author

Brauer N, Maruta Y, Lisci M, Strege K, Oschlies I, Nakamura H, Böhm S, Lehmberg K, Brandhoff L, Ehl S, Parvaneh N, Klapper W, Fukuda M, Griffiths GM, Hennies HC, Niehues T, and Ammann S

Subjects
Humans, Blister, Energy Metabolism, Genotype, rab27 GTP-Binding Proteins genetics, Acyl-CoA Dehydrogenases, Immunologic Deficiency Syndromes genetics, Lymphoma, Primary Immunodeficiency Diseases genetics
Abstract

Introduction: Inborn errors of immunity (IEI) are characterized by a dysfunction of the immune system leading to increased susceptibility to infections, impaired immune regulation and cancer. We present a unique consanguineous family with a history of Hodgkin lymphoma, impaired EBV control and a late onset hemophagocytic lymphohistiocytosis (HLH)., Methods and Results: Overall, family members presented with variable impairment of NK cell and cytotoxic T cell degranulation and cytotoxicity. Exome sequencing identified homozygous variants in RAB27A , FBP1 ( Fructose-1,6-bisphosphatase 1 ) and ACAD9 ( Acyl-CoA dehydrogenase family member 9 ). Variants in RAB27A lead to Griscelli syndrome type 2, hypopigmentation and HLH predisposition., Discussion: Lymphoma is frequently seen in patients with hypomorphic mutations of genes predisposing to HLH. We hypothesize that the variants in FBP1 and ACAD9 might aggravate the clinical and immune phenotype, influence serial killing and lytic granule polarization by CD8 T cells. Understanding of the interplay between the multiple variants identified by whole exome sequencing (WES) is essential for correct interpretation of the immune phenotype and important for critical treatment decisions., Competing Interests: KS is an employee of AstraZeneca and has stock ownership and/or stock options or interests in the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brauer, Maruta, Lisci, Strege, Oschlies, Nakamura, Böhm, Lehmberg, Brandhoff, Ehl, Parvaneh, Klapper, Fukuda, Griffiths, Hennies, Niehues and Ammann.)

Published
2023
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28. Investigators at Oman Medical Specialty Board Discuss Findings in Type 1 Diabetes (Very Long-chain Acyl-coa Dehydrogenase Deficiency and Type I Diabetes Mellitus: Case Report and Management Challenges).

Abstract

Muscat, Oman, Asia, Acyl-CoA Dehydrogenases, Dehydrogenase, Diabetes Mellitus, Endocrine System Diseases and Conditions, Endocrinology, Enzymes and Coenzymes, Flavoproteins, Glucose Metabolism Disorders, Health and Medicine, Insulin Dependent Diabetes Mellitus, Metabolic Diseases and Conditions, Nutritional and Metabolic Diseases and Conditions, Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Peptide Hormones, Peptide Proteins, Proinsulin, Proteins, Risk and Prevention, Type 1 Diabetes, Long-Chain Acyl-CoA Dehydrogenase Keywords: Muscat; Oman; Asia; Acyl-CoA Dehydrogenases; Dehydrogenase; Diabetes Mellitus; Endocrine System Diseases and Conditions; Endocrinology; Enzymes and Coenzymes; Flavoproteins; Glucose Metabolism Disorders; Health and Medicine; Insulin Dependent Diabetes Mellitus; Long-Chain Acyl-CoA Dehydrogenase; Metabolic Diseases and Conditions; Nutritional and Metabolic Diseases and Conditions; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Peptide Hormones; Peptide Proteins; Proinsulin; Proteins; Risk and Prevention; Type 1 Diabetes EN Muscat Oman Asia Acyl-CoA Dehydrogenases Dehydrogenase Diabetes Mellitus Endocrine System Diseases and Conditions Endocrinology Enzymes and Coenzymes Flavoproteins Glucose Metabolism Disorders Health and Medicine Insulin Dependent Diabetes Mellitus Long-Chain Acyl-CoA Dehydrogenase Metabolic Diseases and Conditions Nutritional and Metabolic Diseases and Conditions Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Peptide Hormones Peptide Proteins Proinsulin Proteins Risk and Prevention Type 1 Diabetes 133 133 1 07/17/23 20230717 NES 230717 2023 JUL 17 (NewsRx) -- By a News Reporter-Staff News Editor at Diabetes Week -- Data detailed on Nutritional and Metabolic Diseases and Conditions - Type 1 Diabetes have been presented. [Extracted from the article]

Published
2023

29. Findings from Division of Genetics and Genomic Medicine Advance Knowledge in Sudden Cardiac Death [Postmortem diagnosis of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency in a neonate with sudden cardiac death].

Subjects
CARDIAC arrest, ACYL coenzyme A, POSTMORTEM changes, GENETICS, NEWBORN infants, AUTOPSY
Abstract

For more information on this research see: Postmortem diagnosis of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency in a neonate with sudden cardiac death. Keywords: Acyl-CoA Dehydrogenases; Cardiology; Dehydrogenase; Diagnostics and Screening; Enzymes and Coenzymes; Flavoproteins; Health and Medicine; Long-Chain Acyl-CoA Dehydrogenase; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Proteins; Sudden Cardiac Death EN Acyl-CoA Dehydrogenases Cardiology Dehydrogenase Diagnostics and Screening Enzymes and Coenzymes Flavoproteins Health and Medicine Long-Chain Acyl-CoA Dehydrogenase Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Proteins Sudden Cardiac Death 242 242 1 07/17/23 20230717 NES 230717 2023 JUL 17 (NewsRx) -- By a News Reporter-Staff News Editor at Cardiovascular Week -- Research findings on sudden cardiac death are discussed in a new report. [Extracted from the article]

Published
2023

30. Researcher at Uppsala University Describes Research in Flavoproteins (Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency).

Abstract

Acyl-CoA Dehydrogenases, Dehydrogenase, Enzymes and Coenzymes, Flavoproteins, Glucagon, Health and Medicine, Hormones, Long-Chain Acyl-CoA Dehydrogenase, Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Peptide Hormones, Peptide Proteins, Proglucagon, Proteins Keywords: Acyl-CoA Dehydrogenases; Dehydrogenase; Enzymes and Coenzymes; Flavoproteins; Glucagon; Health and Medicine; Hormones; Long-Chain Acyl-CoA Dehydrogenase; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Peptide Hormones; Peptide Proteins; Proglucagon; Proteins EN Acyl-CoA Dehydrogenases Dehydrogenase Enzymes and Coenzymes Flavoproteins Glucagon Health and Medicine Hormones Long-Chain Acyl-CoA Dehydrogenase Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Peptide Hormones Peptide Proteins Proglucagon Proteins 1743 1743 1 07/10/23 20230714 NES 230714 2023 JUL 14 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Research findings on flavoproteins are discussed in a new report. [Extracted from the article]

Published
2023

31. Data from University of Pittsburgh Broaden Understanding of Oxidoreductases Acting on CH-CH Group Donors (Messenger RNA rescues medium-chain acyl-CoA dehydrogenase deficiency in fibroblasts from patients and a murine model).

Abstract

Transfection of hMCAD mRNA into MCAD deficient patient cells resulted in an increased MCAD protein that localized to mitochondria, concomitant with increased enzyme activity in cell extracts. Keywords: Acyl-CoA Dehydrogenases; Connective Tissue Cells; Dehydrogenase; Enzymes and Coenzymes; Fibroblasts; Genetics; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors EN Acyl-CoA Dehydrogenases Connective Tissue Cells Dehydrogenase Enzymes and Coenzymes Fibroblasts Genetics Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors 407 407 1 05/29/23 20230602 NES 230602 2023 JUN 2 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- New research on oxidoreductases acting on CH-CH group donors is the subject of a new report. [Extracted from the article]

Published
2023

32. New Flavoproteins Study Findings Recently Were Reported by Researchers at Nationwide Children's Hospital [Medium-chain Acyl-coa Dehydrogenase Deficiency (Mcadd) Precipitating Unexpected Death In an Infant: Report of a Case and a Brief Review of...].

Abstract

Keywords: Columbus; State:Ohio; United States; North and Central America; Acyl-CoA Dehydrogenases; Dehydrogenase; Enzymes and Coenzymes; Flavoproteins; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Proteins EN Columbus State:Ohio United States North and Central America Acyl-CoA Dehydrogenases Dehydrogenase Enzymes and Coenzymes Flavoproteins Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Proteins 742 742 1 05/15/23 20230519 NES 230519 2023 MAY 19 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- Data detailed on Proteins - Flavoproteins have been presented. Columbus, State:Ohio, United States, North and Central America, Dehydrogenase, Enzymes and Coenzymes, Flavoproteins, Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Proteins, Acyl-CoA Dehydrogenases. [Extracted from the article]

Published
2023

33. Research on Hypoparathyroidism Detailed by a Researcher at University Hospital 12 de Octubre (Hypoparathyroidism and medium-chain Acyl-CoA dehydrogenase deficiency, an unusual association).

Abstract

Acyl-CoA Dehydrogenases, Dehydrogenase, Endocrine System Diseases and Conditions, Endocrinology, Enzymes and Coenzymes, Flavoproteins, Health and Medicine, Hypoparathyroidism, Oxidoreductases Acting on CH-CH Group Donors, Parathyroid Diseases and Conditions, Proteins, Oxidoreductases Keywords: Acyl-CoA Dehydrogenases; Dehydrogenase; Endocrine System Diseases and Conditions; Endocrinology; Enzymes and Coenzymes; Flavoproteins; Health and Medicine; Hypoparathyroidism; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Parathyroid Diseases and Conditions; Proteins EN Acyl-CoA Dehydrogenases Dehydrogenase Endocrine System Diseases and Conditions Endocrinology Enzymes and Coenzymes Flavoproteins Health and Medicine Hypoparathyroidism Oxidoreductases Oxidoreductases Acting on CH-CH Group Donors Parathyroid Diseases and Conditions Proteins 1562 1562 1 04/10/23 20230414 NES 230414 2023 APR 14 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- New research on hypoparathyroidism is the subject of a new report. Keywords for this news article include: University Hospital 12 de Octubre, Madrid, Spain, Europe, Endocrinology, Flavoproteins, Hypoparathyroidism, Health and Medicine, Enzymes and Coenzymes, Acyl-CoA Dehydrogenases, Parathyroid Diseases and Conditions, Endocrine System Diseases and Conditions, Oxidoreductases Acting on CH-CH Group Donors. [Extracted from the article]

Published
2023

34. Dynamics of acylcarnitines, hypoglycin A, méthylènecyclopropylglycine and their metabolites in a Kladruber stallion with atypical myopathy.

Author

Jahn P, Dobešová D, Brumarová R, Tóthová K, Kopecká A, and Friedecký D

Subjects
Animals, Carnitine analogs & derivatives, Creatine Kinase, Cyclopropanes, Fatty Acids, Glycine analogs & derivatives, Horses, Hypoglycins, Male, Acyl-CoA Dehydrogenases, Horse Diseases diagnosis, Muscular Diseases diagnosis, Muscular Diseases veterinary
Abstract

Equine atypical myopathy (AM also referred to as multiple acyl-CoA dehydrogenases deficiency [MADD]) is thought to be caused by toxins metabolized from hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG). HGA is contained in the seeds and seedlings of the sycamore tree ( Acer pseudoplatanus ); MCPrG has so far only been confirmed in seeds. Among other things, these substances can disrupt the fatty acids β-oxidation pathway with the subsequent accumulation of certain acylcarnitines. The tentative diagnosis is based on anamnesis and clinical signs and can be verified by the detection of elevated creatine kinase activity, specific profile of acylcarnitines and the presence of HGA, MCPrG conjugates and/or their metabolites in peripheral blood and/or urine. Dry blood spots were collected for 15 days from a 3.5-year-old stallion which had been affected by AM and, as a control group, from twelve healthy horses. Two mass spectrometry methods were used for the analysis of 31 acylcarnitines, carnitine, HGA, MCPrG and their metabolites. HGA and six increased acylcarnitines were detected in the patient's blood throughout the monitoring period. Nine acylcarnitines were strongly correlated with HGA. Multivariate statistical analysis showed a clear separation of samples from the AM horse, where the metabolic profile tended to normalization in the later days after intoxication. Due to the longer persistence in the blood, the detection of HGA and elevated acylcarnitines profile appear to be an appropriate tool to confirm the diagnosis of AM, compared to metabolic products of HGA and MCPrG even in advanced cases.

Published
2022
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35. Bioconversion of Phytosterols to 9-Hydroxy-3-Oxo-4,17-Pregadiene-20-Carboxylic Acid Methyl Ester by Enoyl-CoA Deficiency and Modifying Multiple Genes in Mycolicibacterium neoaurum.

Author

Yuan C, Song S, He J, Zhang J, Liu X, Pena EL, Sun J, Shi J, Su Z, and Zhang B

Subjects
Oxidoreductases metabolism, Enoyl-CoA Hydratase genetics, Enoyl-CoA Hydratase metabolism, Steroids metabolism, Acyl Coenzyme A, Carboxylic Acids, Ketosteroids, Esters, Phytosterols metabolism, Prodrugs, Acyl-CoA Dehydrogenases
Abstract

Steroid drug precursors, including C19 and C22 steroids, are crucial to steroid drug synthesis and development. However, C22 steroids are less developed due to the intricacy of the steroid metabolic pathway. In this study, a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), was successfully obtained from Mycolicibacterium neoaurum by 3-ketosteroid-Δ 1 -dehydrogenase and enoyl-CoA hydratase ChsH deficiency. The production of 9-OH-PDCE was improved by the overexpression of 17β-hydroxysteroid dehydrogenase Hsd4A and acyl-CoA dehydrogenase ChsE1-ChsE2 to reduce the accumulation of by-products. The purity of 9-OH-PDCE in fermentation broth was improved from 71.7% to 89.7%. Hence, the molar yield of 9-OH-PDCE was improved from 66.7% to 86.7%, with a yield of 0.78 g/L. Furthermore, enoyl-CoA hydratase ChsH1-ChsH2 was identified to form an indispensable complex in Mycolicibacterium neoaurum DSM 44704. IMPORTANCE C22 steroids are valuable precursors for steroid drug synthesis, but the development of C22 steroids remains unsatisfactory. This study presented a strategy for the one-step bioconversion of phytosterols to a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), by 3-ketosteroid-Δ 1 -dehydrogenase and enoyl-CoA hydratase deficiency with overexpression of 17β-hydroxysteroid dehydrogenase acyl-CoA dehydrogenase in Mycolicibacterium . The function of the enoyl-CoA hydratase ChsH in vivo was revealed. Construction of the novel C22 steroid drug precursor producer provided more potential for steroid drug synthesis, and the characterization of the function of ChsH and the transformation of steroids further revealed the steroid metabolic pathway.

Published
2022
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36. Histone H3K9 butyrylation is regulated by dietary fat and stress via an Acyl-CoA dehydrogenase short chain-dependent mechanism

Author

Zhi Yang, Maha Abdellatif, Julianne Austin, Minzhen He, and Jessica Pfleger

Subjects
0301 basic medicine, 030209 endocrinology & metabolism, Histones, H3K9Bu, ACADS, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Acyl-CoA Dehydrogenases, Stress, Physiological, Gene expression, Animals, Humans, butyrylation, Epigenetics, Internal medicine, Molecular Biology, Fatty acid synthesis, chemistry.chemical_classification, Mice, Inbred BALB C, H3K9Ac, biology, Chemistry, Acyl CoA dehydrogenase, Fatty acid, Acetylation, Cell Biology, RC31-1245, Dietary Fats, Chromatin, Cell biology, Mice, Inbred C57BL, Cardiac hypertrophy, 030104 developmental biology, Histone, biology.protein, Original Article
Abstract

Objective We previously reported that β-oxidation enzymes are present in the nucleus in close proximity to transcriptionally active promoters. Thus, we hypothesized that the fatty acid intermediate, butyryl-CoA, is the substrate for histone butyrylation and its abundance is regulated by acyl-CoA dehydrogenase short chain (ACADS). The objective of this study was to determine the genomic distribution of H3K9-butyryl (H3K9Bu) and its regulation by dietary fat, stress, and ACADS and its impact on gene expression. Methods and results Using genome-wide chromatin immunoprecipitation-sequencing (ChIP–Seq), we show that H3K9Bu is abundant at all transcriptionally active promoters, where, paradoxically, it is most enriched in mice fed a fat-free vs high-fat diet. Deletion of fatty acid synthetase (FASN) abolished H3K9Bu in cells maintained in a glucose-rich but not fatty acid-rich medium, signifying that fatty acid synthesis from carbohydrates substitutes for dietary fat as a source of butyryl-CoA. A high-fat diet induced an increase in ACADS expression that accompanied the decrease in H3K9Bu. Conversely, the deletion of ACADS increased H3K9Bu in human cells and mouse hearts and reversed high-fat- and stress-induced reduction in promoter-H3K9Bu, whose abundance coincided with diminished stress-regulated gene expression as revealed by RNA sequencing. In contrast, H3K9-acetyl (H3K9Ac) abundance was minimally impacted by diet. Conclusion Promoter H3K9 butyrylation is a major histone modification that is negatively regulated by high fat and stress in an ACADS-dependent fashion and moderates stress-regulated gene expression., Highlights • H3K9-butyryl is abundant at all active promoters. • A high-fat diet and stress reduce promoter-H3K9-butyryl but not H3K9-acetyl. • Fatty acid synthesis from glucose substitutes for dietary fat as a source of H3K9-butyryl. • Knockout of ACADS increases levels of H3K9-butyryl. • Promoter-H3K9-butyryl inversely correlates with stress-induced changes in gene expression.

Published
2021

37. Identification of Differential Expression Genes between Volume and Pressure Overloaded Hearts Based on Bioinformatics Analysis.

Author

Fu Y, Zhao D, Zhou Y, Lu J, Kang L, Jiang X, Xu R, Ding Z, and Zou Y

Subjects
Animals, Biomarkers, Fatty Acids, Gene Expression Profiling methods, Mice, PPAR alpha, Acyl-CoA Dehydrogenases, Computational Biology methods
Abstract

Volume overload (VO) and pressure overload (PO) are two common pathophysiological conditions associated with cardiac disease. VO, in particular, often occurs in a number of diseases, and no clinically meaningful molecular marker has yet been established. We intend to find the main differential gene expression using bioinformatics analysis. GSE97363 and GSE52796 are the two gene expression array datasets related with VO and PO, respectively. The LIMMA algorithm was used to identify differentially expressed genes (DEGs) of VO and PO. The DEGs were divided into three groups and subjected to functional enrichment analysis, which comprised GO analysis, KEGG analysis, and the protein-protein interaction (PPI) network. To validate the sequencing data, cardiomyocytes from AR and TAC mouse models were used to extract RNA for qRT-PCR. The three genes with random absolute values of LogFC and indicators of heart failure (natriuretic peptide B, NPPB ) were detected: carboxylesterase 1D ( CES1D ), whirlin ( WHRN ), and WNK lysine deficient protein kinase 2 ( WNK2 ). The DEGs in VO and PO were determined to be 2761 and 1093, respectively, in this study. Following the intersection, 305 genes were obtained, 255 of which expressed the opposing regulation and 50 of which expressed the same regulation. According to the GO and pathway enrichment studies, DEGs with opposing regulation are mostly common in fatty acid degradation, propanoate metabolism, and other signaling pathways. Finally, we used Cytoscape's three techniques to identify six hub genes by intersecting 255 with the opposite expression and constructing a PPI network. Peroxisome proliferator-activated receptor ( PPARα ), acyl-CoA dehydrogenase medium chain ( ACADM ), patatin-like phospholipase domain containing 2 ( PNPLA2 ), isocitrate dehydrogenase 3 ( IDH3 ), heat shock protein family D member 1 ( HSPD1 ), and dihydrolipoamide S-acetyltransferase ( DLAT ) were identified as six potential genes. Furthermore, we predict that the hub genes PPARα , ACADM , and PNPLA2 regulate VO myocardial changes via fatty acid metabolism and acyl-Coa dehydrogenase activity, and that these genes could be employed as basic biomarkers for VO diagnosis and treatment.

Published
2022
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38. Lnc-SMaRT Translational Regulation of Spire1, A New Player in Muscle Differentiation.

Author

Scalzitti S, Mariani D, Setti A, Colantoni A, Lisi M, Bozzoni I, and Martone J

Subjects
Acyl-CoA Dehydrogenases, Animals, DEAD-box RNA Helicases, G-Quadruplexes, Gene Expression Regulation, Developmental, Humans, Mice, Microfilament Proteins genetics, Nerve Tissue Proteins genetics, Protein Conformation, RNA Processing, Post-Transcriptional, RNA, Long Noncoding genetics, RNA, Messenger, RNA-Binding Proteins metabolism, Transcription Factors genetics, Transcription Factors metabolism, Cell Differentiation genetics, Microfilament Proteins metabolism, Muscle Development genetics, Muscle Development physiology, Muscles physiology, Nerve Tissue Proteins metabolism
Abstract

The destiny of a messenger RNA is determined from a combination of in cis elements, like peculiar secondary structures, and in trans modulators, such as RNA binding proteins and non-coding, regulatory RNAs. RNA guanine quadruplexes belong to the first group: these strong secondary structures have been characterized in many mRNAs, and their stabilization or unwinding provides an additional step for the fine tuning of mRNA stability and translation. On the other hand, many cytoplasmic long non-coding RNAs intervene in post-transcriptional regulation, frequently by direct base-pairing with their mRNA targets. We have previously identified the lncRNA SMaRT as a key modulator of the correct timing of murine skeletal muscle differentiation; when expressed, lnc-SMaRT interacts with a G-quadruplex-containing region of Mlx-γ mRNA, therefore inhibiting its translation by counteracting the DHX36 helicase activity. The "smart" mode of action of lnc-SMaRT led us to speculate whether this molecular mechanism could be extended to other targets and conserved in other species. Here, we show that the molecular complex composed by lnc-SMaRT and DHX36 also includes other mRNAs. We prove that lnc-SMaRT is able to repress Spire1 translation through base-pairing with its G-quadruplex-forming sequence, and that Spire1 modulation participates to the regulation of proper skeletal muscle differentiation. Moreover, we demonstrate that the interaction between DHX36 and lnc-SMaRT is indirect and mediated by the mRNAs present in the complex. Finally, we suggest an extendibility of the molecular mechanism of lnc-SMaRT from the mouse model to humans, identifying potential functional analogues., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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39. Structural Basis of Cyclic 1,3-Diene Forming Acyl-Coenzyme A Dehydrogenases.

Author

Kung JW, Meier AK, Willistein M, Weidenweber S, Demmer U, Ermler U, and Boll M

Subjects
Acyl-CoA Dehydrogenases chemistry, Alkadienes chemistry, Biocatalysis, Models, Molecular, Molecular Structure, Acyl-CoA Dehydrogenases metabolism, Alkadienes metabolism
Abstract

The biologically important, FAD-containing acyl-coenzyme A (CoA) dehydrogenases (ACAD) usually catalyze the anti-1,2-elimination of a proton and a hydride of aliphatic CoA thioesters. Here, we report on the structure and function of an ACAD from anaerobic bacteria catalyzing the unprecedented 1,4-elimination at C3 and C6 of cyclohex-1-ene-1-carboxyl-CoA (Ch1CoA) to cyclohex-1,5-diene-1-carboxyl-CoA (Ch1,5CoA) and at C3 and C4 of the latter to benzoyl-CoA. Based on high-resolution Ch1CoA dehydrogenase crystal structures, the unorthodox reactivity is explained by the presence of a catalytic aspartate base (D91) at C3, and by eliminating the catalytic glutamate base at C1. Moreover, C6 of Ch1CoA and C4 of Ch1,5CoA are positioned towards FAD-N5 to favor the biologically relevant C3,C6- over the C3,C4-dehydrogenation activity. The C1,C2-dehydrogenation activity was regained by structure-inspired amino acid exchanges. The results provide the structural rationale for the extended catalytic repertoire of ACADs and offer previously unknown biocatalytic options for the synthesis of cyclic 1,3-diene building blocks., (© 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Published
2021
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