Lipid Deposition and Metabolism in Local and Modern Pig Breeds: a Review
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PEX5 Regulates Autophagy Via the Mtorc1-TFEB Axis During Starvation
Eun et al. Experimental & Molecular Medicine (2018) 50:4 DOI 10.1038/s12276-017-0007-8 Experimental & Molecular Medicine ARTICLE Open Access PEX5 regulates autophagy via the mTORC1-TFEB axis during starvation So Young Eun1,JoonNoLee2,In-KooNam2, Zhi-qiang Liu1,Hong-SeobSo 1, Seong-Kyu Choe1 and RaeKil Park2 Abstract Defects in the PEX5 gene impair the import of peroxisomal matrix proteins, leading to nonfunctional peroxisomes and other associated pathological defects such as Zellweger syndrome. Although PEX5 regulates autophagy process in a stress condition, the mechanisms controlling autophagy by PEX5 under nutrient deprivation are largely unknown. Herein, we show a novel function of PEX5 in the regulation of autophagy via Transcription Factor EB (TFEB). Under serum-starved conditions, when PEX5 is depleted, the mammalian target of rapamycin (mTORC1) inhibitor TSC2 is downregulated, which results in increased phosphorylation of the mTORC1 substrates, including 70S6K, S6K, and 4E- BP-1. mTORC1 activation further suppresses the nuclear localization of TFEB, as indicated by decreased mRNA levels of TFEB, LIPA, and LAMP1. Interestingly, peroxisomal mRNA and protein levels are also reduced by TFEB inactivation, indicating that TFEB might control peroxisome biogenesis at a transcriptional level. Conversely, pharmacological inhibition of mTOR resulting from PEX5 depletion during nutrient starvation activates TFEB by promoting nuclear localization of the protein. In addition, mTORC1 inhibition recovers the damaged-peroxisome biogenesis. These data suggest that PEX5 may be a critical regulator of lysosomal gene expression and autophagy through the mTOR-TFEB- autophagy axis under nutrient deprivation. 1234567890():,; 1234567890():,; Introduction Mitochondrial antiviral-signaling protein (MAVS) func- Peroxisome is an essential cellular organelle for per- tions as an antiviral signaling platform to induce the forming various metabolic activities, including oxidation interferon-independent signaling pathways4. -
Fatty Acid Biosynthesis
BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbon Assimilation – Calvin Cycle Carbohydrate Biosynthesis in Animals Gluconeogenesis Glycogen Synthesis Pentose-Phosphate Pathway Regulation of Carbohydrate Metabolism Anaplerotic reactions Biosynthesis of Fatty Acids and Lipids Fatty Acids contrasts Diversification of fatty acids location & transport Eicosanoids Synthesis Prostaglandins and Thromboxane acetyl-CoA carboxylase Triacylglycerides fatty acid synthase ACP priming Membrane lipids 4 steps Glycerophospholipids Control of fatty acid metabolism Sphingolipids Isoprene lipids: Cholesterol ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1 ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1. Biosynthesis of fatty acids 2. Regulation of fatty acid degradation and synthesis 3. Assembly of fatty acids into triacylglycerol and phospholipids 4. Metabolism of isoprenes a. Ketone bodies and Isoprene biosynthesis b. Isoprene polymerization i. Cholesterol ii. Steroids & other molecules iii. Regulation iv. Role of cholesterol in human disease ANABOLISM II: Biosynthesis of Fatty Acids & Lipids Lipid Fat Biosynthesis Catabolism Fatty Acid Fatty Acid Degradation Synthesis Ketone body Isoprene Utilization Biosynthesis 2 Catabolism Fatty Acid Biosynthesis Anabolism • Contrast with Sugars – Lipids have have hydro-carbons not carbo-hydrates – more reduced=more energy – Long-term storage vs short-term storage – Lipids are essential for structure in ALL organisms: membrane phospholipids • Catabolism of fatty acids –produces acetyl-CoA –produces reducing -
Peroxisomal Disorders and Their Mouse Models Point to Essential Roles of Peroxisomes for Retinal Integrity
International Journal of Molecular Sciences Review Peroxisomal Disorders and Their Mouse Models Point to Essential Roles of Peroxisomes for Retinal Integrity Yannick Das, Daniëlle Swinkels and Myriam Baes * Lab of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium; [email protected] (Y.D.); [email protected] (D.S.) * Correspondence: [email protected] Abstract: Peroxisomes are multifunctional organelles, well known for their role in cellular lipid homeostasis. Their importance is highlighted by the life-threatening diseases caused by peroxisomal dysfunction. Importantly, most patients suffering from peroxisomal biogenesis disorders, even those with a milder disease course, present with a number of ocular symptoms, including retinopathy. Patients with a selective defect in either peroxisomal α- or β-oxidation or ether lipid synthesis also suffer from vision problems. In this review, we thoroughly discuss the ophthalmological pathology in peroxisomal disorder patients and, where possible, the corresponding animal models, with a special emphasis on the retina. In addition, we attempt to link the observed retinal phenotype to the underlying biochemical alterations. It appears that the retinal pathology is highly variable and the lack of histopathological descriptions in patients hampers the translation of the findings in the mouse models. Furthermore, it becomes clear that there are still large gaps in the current knowledge on the contribution of the different metabolic disturbances to the retinopathy, but branched chain fatty acid accumulation and impaired retinal PUFA homeostasis are likely important factors. Citation: Das, Y.; Swinkels, D.; Baes, Keywords: peroxisome; Zellweger; metabolism; fatty acid; retina M. Peroxisomal Disorders and Their Mouse Models Point to Essential Roles of Peroxisomes for Retinal Integrity. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Activation of Pparα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis
Tohoku J. Exp. Med., 2016, 240, 113-122PPARα Activation in Cells due to VLCAD Deficiency 113 Activation of PPARα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis * * Yang Yang,1, Yuyao Feng,1, Xiaowei Zhang,2 Takero Nakajima,1 Naoki Tanaka,1 Eiko Sugiyama,3 Yuji Kamijo4 and Toshifumi Aoyama1 1Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan 2Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China 3Department of Nutritional Science, Nagano Prefectural College, Nagano, Nagano, Japan 4Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first reaction in the mitochondrial fatty acid β-oxidation pathway. VLCAD deficiency is associated with the accumulation of fat in multiple organs and tissues, which results in specific clinical features including cardiomyopathy, cardiomegaly, muscle weakness, and hepatic dysfunction in infants. We speculated that the abnormal fatty acid metabolism in VLCAD-deficient individuals might cause cell necrosis by fatty acid toxicity. The accumulation of fatty acids may activate peroxisome proliferator-activated receptor (PPAR), a master regulator of fatty acid metabolism and a potent nuclear receptor for free fatty acids. We examined six skin fibroblast lines, derived from VLCAD-deficient patients and identified fatty acid accumulation and PPARα activation in these cell lines. We then found that the expression levels of three enzymes involved in fatty acid degradation, including long-chain acyl-CoA synthetase (LACS), were increased in a PPARα-dependent manner. This increased expression of LACS might enhance the fatty acyl-CoA supply to fatty acid degradation and sulfatide synthesis pathways. -
Application of Microrna Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease
Article Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease Jennifer L. Major, Rushita A. Bagchi * and Julie Pires da Silva * Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected] (R.A.B.); [email protected] (J.P.d.S.) Supplementary Tables Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 www.mdpi.com/journal/mps Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 2 of 25 Table 1. List of all hsa-miRs identified by Human microRNA Disease Database (HMDD; v3.2) analysis. hsa-miRs were identified using the term “genetics” and “circulating” as input in HMDD. Targets CAD hsa-miR-1 Targets IR injury hsa-miR-423 Targets Obesity hsa-miR-499 hsa-miR-146a Circulating Obesity Genetics CAD hsa-miR-423 hsa-miR-146a Circulating CAD hsa-miR-149 hsa-miR-499 Circulating IR Injury hsa-miR-146a Circulating Obesity hsa-miR-122 Genetics Stroke Circulating CAD hsa-miR-122 Circulating Stroke hsa-miR-122 Genetics Obesity Circulating Stroke hsa-miR-26b hsa-miR-17 hsa-miR-223 Targets CAD hsa-miR-340 hsa-miR-34a hsa-miR-92a hsa-miR-126 Circulating Obesity Targets IR injury hsa-miR-21 hsa-miR-423 hsa-miR-126 hsa-miR-143 Targets Obesity hsa-miR-21 hsa-miR-223 hsa-miR-34a hsa-miR-17 Targets CAD hsa-miR-223 hsa-miR-92a hsa-miR-126 Targets IR injury hsa-miR-155 hsa-miR-21 Circulating CAD hsa-miR-126 hsa-miR-145 hsa-miR-21 Targets Obesity hsa-mir-223 hsa-mir-499 hsa-mir-574 Targets IR injury hsa-mir-21 Circulating IR injury Targets Obesity hsa-mir-21 Targets CAD hsa-mir-22 hsa-mir-133a Targets IR injury hsa-mir-155 hsa-mir-21 Circulating Stroke hsa-mir-145 hsa-mir-146b Targets Obesity hsa-mir-21 hsa-mir-29b Methods Protoc. -
Targeting Demyelination and Virtual Hypoxia with High-Dose Biotin As a Treatment for Progressive Multiple Sclerosis
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuropharmacology 110 (2016) 644e653 Contents lists available at ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm Invited review Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis * Fred eric Sedel a, , Delphine Bernard a, Donald M. Mock b, c, Ayman Tourbah d a MedDay Pharmaceuticals, ICM-Brain and Spine Institute-IPEPs, Groupe Hospitalier Pitie Salp^etriere, 47 Boulevard de l'Hopital, 75013 Paris, France b Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA c Department of Pediatrics, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA d Department of Neurology and FacultedeMedecine de Reims, CHU de Reims, URCA, 45 Rue Cognacq Jay, 51092 Reims Cedex, France article info abstract Article history: Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective Received 7 April 2015 treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected Received in revised form individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve 24 July 2015 objective measures of MS-related disability. In this article, we review the biology of biotin and explore Accepted 18 August 2015 the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients Available online 5 September 2015 with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. -
Fatty Acid Degradation Monounsaturated Fatty Acids
BI/CH 422/622 OUTLINE: OUTLINE: Lipid Degradation (Catabolism) Protein Degradation (Catabolism) FOUR stages in the catabolism of lipids: Digestion Mobilization from tissues (mostly adipose) Inside of cells hormone regulated Protein turnover specific lipases Ubiquitin glycerol Proteosome Activation of fatty acids Amino-Acid Degradation Fatty-acyl CoA Synthetase Transport into mitochondria carnitine Oxidation rationale Saturated FA 4 steps dehydrogenation hydration oxidation thiolase energetics Unsaturated FA Odd-chain FA Ketone Bodies Other organelles Fatty Acid Degradation Monounsaturated Fatty Acids cis trans During first of five ⦚ ⦚ ⦚ ⦚ ⦚ remaining cycles, acyl- CoA dehydrogenase step is skipped, resulting in 1 fewer FADH2. 1 Fatty Acid Degradation Energy from Fatty Acid Catabolism TABLE 17-1a Yield of ATP during Oxidation of One Molecule of PalmitoylOleoyl--CoA to CO2 and H2O Number of NADH or Number of ATP a Enzyme catalyzing the oxidation step FADH2 formed ultimately formed β Oxidation Acyl-CoA dehydrogenase 7 FADH2 10.5 β-Hydroxyacyl-CoA dehydrogenase 8 NADH 20 Citric acid cycle 35 à87.5 ATP Isocitrate dehydrogenase 9 NADH 22.5 α-Ketoglutarate dehydrogenase 9 NADH 22.5 Succinyl-CoA synthetase 16 9b Succinate dehydrogenase à24 ATP 9 FADH2 13.5 Malate dehydrogenase 9 NADH 22.5 Total 120.5 – 2 = 118.5* aThese calculations assume that mitochondrial oxidative phosphorylation produces 1.5 ATP per FADH2 oxidized and 2.5 ATP per NADH oxidized. bGTP produced directly in this step yields ATP in the reaction catalyzed by nucleoside diphosphate kinase (p. 516). *These 2 ”ATP” equivalents were expended in the activation by Fatty acyl–CoA synthetase. Fatty Acid Degradation Oxidation of Polyunsaturated Fatty Acids Results in 1 fewer FADH2 after isomerization, as the acyl-CoA dehydrogenase step is skipped and goes right to the hydratase. -
Rapid Whole Genome Sequencing Identifies a Homozygous Novel Variant, His540arg, in HSD17B4 Resulting in D-Bifunctional Protein Deficiency Disorder Diagnosis
Downloaded from molecularcasestudies.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press CSH Molecular Case Studies: Rapid Communications Rapid whole genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis. Running title: HSD17B4 His540Arg novel variant Lane Savage ([email protected])1,2*, Stacie D Adams ([email protected])1,3, Kiely James ([email protected])4 , Shimul Chowdhury ([email protected])4 , Surender Rajasekaran ([email protected])1,5,6, Jeremy W. Prokop ([email protected])1,2, Caleb Bupp ([email protected])1,3# 1 Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA 2 Department of Pharmacology and Toxicology, Michigan State University, East Lansing MI 48824, USA 3 Spectrum Health/Helen DeVos Children’s Hospital Medical Genetics, Grand Rapids, 49503, MI, USA 4 Rady Children’s Institute for Genomic Medicine, 7910 Frost Street MC5129, San Diego, CA 92123, USA 5 Pediatric Intensive Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, MI, 49503, USA 6 Office of Research, Spectrum Health, 15 Michigan Street NE, Grand Rapids, MI 49503, USA #Corresponding Author: Caleb Bupp ([email protected]) ABSTRACT (234/250): Rapid whole genome sequencing (rWGS) allows for a diagnosis to be made quickly and impact medical management, particularly in critically ill children. Variants identified by this approach are often not identified using other testing methodologies, such as carrier screening or gene sequencing panels, targeted panels, or chromosomal microarrays. However, rWGS can identify variants of uncertain significance (VUS), which challenges clinicians in the rapid return of information to families. -
Investigations of Anaplerosis from Propionyl-Coa
INVESTIGATIONS OF ANAPLEROSIS FROM PROPIONYL-COA PRECURSORS AND FATTY ACID OXIDATION IN THE BRAIN OF VLCAD AND CONTROL MICE by XIAO WANG Submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Thesis Advisor: Henri Brunengraber, M.D., Ph.D. Department of Nutrition CASE WESTERN RESERVE UNIVERISITY May, 2009 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of _____________________________________________________ candidate for the ______________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Table of Contents Table of Contents.……………………………………………………………….………i List of Table...……………………………………………………………………………v List of Figures.……………………………………………………………………..….…vi Acknowledgements …………………………………..…………………………..….…xi List of Abbreviations……………………………………………………………………xii Abstract………………………………………………………………………………....xvi CHAPTER 1: Substrate Utilization In The Brain 1.1 Overview of brain energy metabolism..…….………………………………….....1 1.2 The blood-brain barrier ……..……….…….………………………………….…... 2 1.3 Utilization of glucose in the brain………………………………………………..…4 1.3.1 -
Role of Catalase in Oxidative Stress-And Age-Associated
Hindawi Oxidative Medicine and Cellular Longevity Volume 2019, Article ID 9613090, 19 pages https://doi.org/10.1155/2019/9613090 Review Article Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases Ankita Nandi,1 Liang-Jun Yan ,2 Chandan Kumar Jana,3 and Nilanjana Das 1 1Department of Biotechnology, Visva-Bharati University, Santiniketan, West Bengal 731235, India 2Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA 3Department of Chemistry, Purash-Kanpur Haridas Nandi Mahavidyalaya, P.O. Kanpur, Howrah, West Bengal 711410, India Correspondence should be addressed to Nilanjana Das; [email protected] Received 25 March 2019; Revised 18 June 2019; Accepted 14 August 2019; Published 11 November 2019 Academic Editor: Cinzia Signorini Copyright © 2019 Ankita Nandi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Reactive species produced in the cell during normal cellular metabolism can chemically react with cellular biomolecules such as nucleic acids, proteins, and lipids, thereby causing their oxidative modifications leading to alterations in their compositions and potential damage to their cellular activities. Fortunately, cells have evolved several antioxidant defense mechanisms (as metabolites, vitamins, and enzymes) to neutralize or mitigate the harmful effect of reactive species and/or their byproducts. Any perturbation in the balance in the level of antioxidants and the reactive species results in a physiological condition called “oxidative stress.” A catalase is one of the crucial antioxidant enzymes that mitigates oxidative stress to a considerable extent by destroying cellular hydrogen peroxide to produce water and oxygen. -
Amino Acid Degradation
BI/CH 422/622 OUTLINE: OUTLINE: Protein Degradation (Catabolism) Digestion Amino-Acid Degradation Inside of cells Protein turnover Dealing with the carbon Ubiquitin Fates of the 29 Activation-E1 Seven Families Conjugation-E2 nitrogen atoms in 20 1. ADENQ Ligation-E3 AA: Proteosome 2. RPH 9 ammonia oxidase Amino-Acid Degradation 18 transamination Ammonia 2 urea one-carbon metabolism free transamination-mechanism to know THF Urea Cycle – dealing with the nitrogen SAM 5 Steps Carbamoyl-phosphate synthetase 3. GSC Ornithine transcarbamylase PLP uses Arginino-succinate synthetase Arginino-succinase 4. MT – one carbon metabolism Arginase 5. FY – oxidase vs oxygenase Energetics Urea Bi-cycle 6. KW – Urea Cycle – dealing with the nitrogen 7. BCAA – VIL Feeding the Urea Cycle Glucose-Alanine Cycle Convergence with Fatty acid-odd chain Free Ammonia Overview Glutamine Glutamate dehydrogenase Overall energetics Amino Acid A. Concepts 1. ConvergentDegradation 2. ketogenic/glucogenic 3. Reactions seen before The SEVEN (7) Families B. Transaminase (A,D,E) / Deaminase (Q,N) Family C. Related to biosynthesis (R,P,H; C,G,S; M,T) 1.Glu Family a. Introduce oxidases/oxygenases b. Introduce one-carbon metabolism (1C) 2.Pyruvate Family a. PLP reactions 3. a-Ketobutyric Family (M,T) a. 1-C metabolism D. Dedicated 1. Aromatic Family (F,Y) a. oxidases/oxygenases 2. a-Ketoadipic Family (K,W) 3. Branched-chain Family (V,I,L) E. Convergence with Fatty Acids: propionyl-CoA 29 N 1 Amino Acid Degradation • Intermediates of the central metabolic pathway • Some amino acids result in more than one intermediate. • Ketogenic amino acids can be converted to ketone bodies.