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metabolizing enzymes defects

Toluwani Tella, Bubuya Masola, Samson Mukaratirwa
Diabetes mellitus is characterized by hyperglycaemia that results from defects in insulin secretion or insulin action and is accompanied by general disturbances metabolism. Psidium guajava (PG) leaf is known to have antidiabetic effects that include lowering of blood glucose. The aim of the study was to investigate the effect of PG leaf extract on tissue activity of glycogen synthase (GS) and glycogen phosphorylase (GP); tissue activity of hormone sensitive lipase (HSL); serum lipid profile; and serum enzyme biomarkers of tissue damage...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tianliang Li, Xinghui Li, Kuldeep S Attri, Changhong Liu, Lupeng Li, Laura E Herring, John M Asara, Yu L Lei, Pankaj K Singh, Chengjiang Gao, Haitao Wen
Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage. However, the role of individual glucose metabolic pathways during viral infection remains largely unknown. Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity. Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation...
December 12, 2018: Cell Host & Microbe
Baishali Alok Jana, Pavan Kumar Chintamaneni, Praveen Thaggikuppe Krishnamurthy, Ashish Wadhwani, Suresh Kumar Mohankumar
Mitochondria play a central role in the energy homeostasis in eukaryotic cells by generating ATP via oxidative metabolism of nutrients. Excess lipid accumulation and impairments in mitochondrial function have been considered as putative mechanisms for the pathogenesis of skeletal muscle insulin resistance. Accumulation of lipids in tissues occurs due to either excessive fatty acid uptake, decreased fatty acid utilization or both. Consequently, elevated levels cytosolic lipid metabolites, triglycerides, diacylglycerol and ceramides have been demonstrated to adversely affect glucose homeostasis...
December 8, 2018: Molecular Biology Reports
Lucie Mádrová, Matyáš Krijt, Veronika Barešová, Jan Václavík, David Friedecký, Dana Dobešová, Olga Součková, Václava Škopová, Tomáš Adam, Marie Zikánová
Purines are essential molecules for all forms of life. In addition to constituting a backbone of DNA and RNA, purines play roles in many metabolic pathways, such as energy utilization, regulation of enzyme activity, and cell signaling. The supply of purines is provided by two pathways: the salvage pathway and de novo synthesis. Although purine de novo synthesis (PDNS) activity varies during the cell cycle, this pathway represents an important source of purines, especially for rapidly dividing cells. A method for the detailed study of PDNS is lacking for analytical reasons (sensitivity) and because of the commercial unavailability of the compounds...
2018: PloS One
Noga Ron-Harel, Giulia Notarangelo, Jonathan M Ghergurovich, Joao A Paulo, Peter T Sage, Daniel Santos, F Kyle Satterstrom, Steven P Gygi, Joshua D Rabinowitz, Arlene H Sharpe, Marcia C Haigis
T cell-mediated immune responses are compromised in aged individuals, leading to increased morbidity and reduced response to vaccination. While cellular metabolism tightly regulates T cell activation and function, metabolic reprogramming in aged T cells has not been thoroughly studied. Here, we report a systematic analysis of metabolism during young versus aged naïve T cell activation. We observed a decrease in the number and activation of naïve T cells isolated from aged mice. While young T cells demonstrated robust mitochondrial biogenesis and respiration upon activation, aged T cells generated smaller mitochondria with lower respiratory capacity...
December 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
Garthiga Manickam, Pierre Moffatt, Monzur Murshed
Sphingomyelin phosphodiesterase 3 (SMPD3), a lipid-metabolizing enzyme present in bone and cartilage, has important roles in the developing skeleton. Using an inducible knockout mouse model, Smpd3flox/flox ;Osx-Cre , where Smpd3 was ablated in both Osx expressing chondrocytes and osteoblasts during early skeletogenesis, we showed that SMPD3 deficiency results in delayed extracellular matrix (ECM) mineralization and severe skeletal deformities. Interestingly, in 3-month-old Smpd3flox/flox ;Osx-Cre mice, in which Smpd3 was ablated postnatally, only a mild bone mineralization defect was observed...
December 10, 2018: Molecular and Cellular Biology
Nasrin Malekpour, Rahim Vakili, Tayebeh Hamzehloie
Objectives: Mucopolysaccharidosis VI (MPS VI) or Maroteaux-Lamy syndrome is a rare metabolic disorder, resulting from the deficient activity of the lysosomal enzyme arylsulfatase B (ARSB). The enzymatic defect of ARSB leads to progressive lysosomal storage disorder and accumulation of glycosaminoglycan (GAG) dermatan sulfate (DS), which causes harmful effects on various organs and tissues and short stature. To date, more than 160 different mutations have been reported in the ARSB gene...
September 2018: Iranian Journal of Basic Medical Sciences
Valeriya V Solovyeva, Alisa A Shaimardanova, Daria S Chulpanova, Kristina V Kitaeva, Lisa Chakrabarti, Albert A Rizvanov
Tay-Sachs disease belongs to the group of autosomal-recessive lysosomal storage metabolic disorders. This disease is caused by β-hexosaminidase A (HexA) enzyme deficiency due to various mutations in α-subunit gene of this enzyme, resulting in GM2 ganglioside accumulation predominantly in lysosomes of nerve cells. Tay-Sachs disease is characterized by acute neurodegeneration preceded by activated microglia expansion, macrophage and astrocyte activation along with inflammatory mediator production. In most cases, the disease manifests itself during infancy, the "infantile form," which characterizes the most severe disorders of the nervous system...
2018: Frontiers in Physiology
Maria M Bayliak, Maria P Lylyk, Dmytro V Gospodaryov, Volodymyr O Kotsyubynsky, Nataliia V Butenko, Kenneth B Storey, Volodymyr I Lushchak
In recent years, Drosophila melanogaster has emerged as a model for studies on aluminum toxicity. The current study aimed to disclose the mechanisms of aluminum toxicity in D. melanogaster at larval and adult stages and examined the potential protective effects of dietary alpha-ketoglutarate (AKG). Flies were reared on food containing 10 mM AlCl3 , 10 mM AKG or both additives. Rearing on an AlCl3 -containing diet induced behavioral defects, and decreased fecundity and long-term survival of female flies...
November 30, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Neeraj Kumar, Heerak Chugh, Damini Sood, Aarushi Singh, Ravi Tomar, Vartika Tomar, Ramesh Chandra
Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis...
November 29, 2018: Current Topics in Medicinal Chemistry
Josef Finsterer
Metabolic myopathies are a heterogeneous group of disorders characterized by inherited defects of enzymatic pathways involved in muscle fiber energetics. Diagnosing metabolic myopathies requires a thoroughly taken individual and family history, a meticulous neurologic exam, exercise tests, blood and urine tests, needle-electromyography, nerve-conduction studies, muscle biopsy, targeted genetic tests, or next-generation sequencing. There is limited evidence from the literature to guide treatment of metabolic myopathies...
December 2018: Expert Review of Neurotherapeutics
Seyho Cem Yucetas, Necati Ucler
Alkaptonuria is a rare metabolic disease caused by deficiency of homogentisic acid oxidase and characterized by bluish-black discoloration of cartilages and skin (ochronosis). Defective production of this enzyme results in the accumulation of homogentisic acid (HGA), a tyrosine degradation product, in the bloodstream. Accumulation of HGA and its metabolites in tissues causes ochronosis. The word ochronosis refers to the dark bluish-black discoloration of connective tissues including the sclera, cornea, auricular cartilage, heart valves, articular cartilage, tendons, and ligaments...
November 26, 2018: Journal of Neurological Surgery. Part A, Central European Neurosurgery
Phillip M Deardorff, Tina B McKay, Siran Wang, Chiara E Ghezzi, Dana M Cairns, Rosalyn D Abbott, James L Funderburgh, Kenneth R Kenyon, David L Kaplan
Diabetes mellitus is a disease caused by innate or acquired insulin deficiency, resulting in altered glucose metabolism and high blood glucose levels. Chronic hyperglycemia is linked to development of several ocular pathologies affecting the anterior segment, including diabetic corneal neuropathy and keratopathy, neovascular glaucoma, edema, and cataracts leading to significant visual defects. Due to increasing disease prevalence, related medical care costs, and visual impairment resulting from diabetes, a need has arisen to devise alternative systems to study molecular mechanisms involved in disease onset and progression...
November 23, 2018: Scientific Reports
Raphaël Tamò, Marianne Rohrbach, Matthias Baumgartner, Felix Beuschlein, Albina Nowak
The basics of lysosomal storage diseases Abstract. Lysosomal storage diseases are comprised of a group of more than 50 genetic disorders which are characterized by a defective lysosomal function. The lysosome is the recycling plant of the cell. Most of the lysosomal storage diseases are caused by a deficient hydrolase. The disturbed metabolism leads to accumulation of complex molecules. The classic classification is by the main storage molecule: Sphingolipidoses, Mucopolysaccharidoses and Glycoproteinosis. The modern classification stretches the definition and includes every disease that has a defect in a lysosomal component, which is needed for the normal function of the lysosome...
November 2018: Therapeutische Umschau. Revue Thérapeutique
Bernd Mensing, Albina Nowak, Sandrine Zweifel, Luigi Terracciano, Christine Bernsmeier, Magdalena Filipowicz Sinnreich
Wilson's disease or hepatolenticular degeneration Abstract. Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism. The most common clinical presentations are liver disease and / or neuro-psychiatric manifestations. Pathophysiologically, Wilson's disease is caused by mutations in the ATP7B gene, which lead to defective biliary excretion of copper and subsequent accumulation of copper in the liver and in other organs. Its prevalence is approximately 1:30 000, however its penetrance, clinical presentation and disease severity vary widely, ranging from asymptomatic elevation of liver enzymes to cirrhosis or acute liver failure with or without neuro-psychiatric symptoms...
November 2018: Therapeutische Umschau. Revue Thérapeutique
Ren-Ai Xu, Er-Min Gu, Teng-Hui Liu, Qiu-Geng Ou-Yang, Guo-Xin Hu, Jian-Ping Cai
Background: CYP/CYP450 2C19 (CYP2C19) is a highly polymorphic enzyme and exhibits individual differences in metabolic activity. The purpose of this research was mainly to explore the catalytic activities of 30 CYP2C19 variants on the substrate voriconazole in vitro, including 24 novel CYP2C19 variants (2C19.2E-.2H, .2J, .3C, .29-.33, L16F, 35FS, R124Q, R125G, T130M, N231T, M255T, R261W, N277K, S303N, I327T, N403I, and A430V) found in Chinese Han population for the first time. Methods: These CYP2C19 variants were expressed in Spodoptera frugiperda ( Sf ) 21 insect cells using the baculovirus-mediated expression system...
2018: Infection and Drug Resistance
Steven J Carlson, Angela Fleig, M Kelsey Baron, Ivan A Berg, Birgit E Alber
Rhodobacter sphaeroides is able to use 3-hydroxypropionate as the sole carbon source through the reductive conversion of 3-hydroxypropionate to propionyl-CoA. The ethylmalonyl-CoA pathway is not required in this process because a crotonyl-CoA carboxylase/reductase (Ccr)-negative mutant still grew with 3-hydroxypropionate. Much to our surprise, a mutant defective for another specific enzyme of the ethylmalonyl-CoA pathway, mesaconyl-CoA hydratase (Mch), lost its ability for 3-hydroxypropionate-dependent growth...
November 19, 2018: Journal of Bacteriology
Henna Konttinen, Irina Gureviciene, Minna Oksanen, Alexandra Grubman, Sanna Loppi, Mikko T Huuskonen, Paula Korhonen, Riikka Lampinen, Meike Keuters, Irina Belaya, Heikki Tanila, Katja M Kanninen, Gundars Goldsteins, Gary Landreth, Jari Koistinaho, Tarja Malm
Astrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source of energy. Defective fatty acid oxidation and mitochondrial dysfunctions correlate with hippocampal neurodegeneration and memory deficits in Alzheimer's disease (AD), but it is unclear whether energy metabolism can be targeted to prevent or treat the disease. Here we show for the first time an impairment in fatty acid oxidation in human astrocytes derived from induced pluripotent stem cells of AD patients...
November 19, 2018: Glia
Cinzia M Bellettato, Maurizio Scarpa
The mucopolysaccharidoses (MPS) are a heterogeneous group of in-born metabolic conditions caused by genetic defects that result in the absence or severe deficiency of one of the lysosomal hydrolases responsible for the degradation of glycosaminoglycans (GAGs). Such enzyme deficiency causes accumulation of GAGs that begins in infancy and progressively worsens, often affecting several organs including the central nervous system (CNS) inducing mental retardation, progressive neurodegeneration, and premature death...
November 16, 2018: Italian Journal of Pediatrics
Laura Poillet-Perez, Xiaoqi Xie, Le Zhan, Yang Yang, Daniel W Sharp, Zhixian Sherrie Hu, Xiaoyang Su, Anurag Maganti, Cherry Jiang, Wenyun Lu, Haiyan Zheng, Marcus W Bosenberg, Janice M Mehnert, Jessie Yanxiang Guo, Edmund Lattime, Joshua D Rabinowitz, Eileen White
Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5 . Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1 . Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7 ...
November 14, 2018: Nature
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