Functional Analysis of BPSS2242 Reveals Its Detoxification Role In
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Isocitrate Dehydrogenase Activity Assay Kit (MAK062)
Isocitrate Dehydrogenase Activity Assay Kit Catalog Number MAK062 Storage Temperature –20 C TECHNICAL BULLETIN Product Description Developer 1 vl Isocitrate dehydrogenase (IDH) catalyzes the Catalog Number MAK062E conversion of isocitrate to -ketoglutarate. In eukaryotes, there are three isozymes of IDH, the IDH Positive Control (NADP+) 20 L mitochondrial IDH2 and IDH3, and the cytoplasmic/ Catalog Number MAK062F peroxisomal IDH1. All three IDH family members require the presence of a divalent cation (Mg2+ or Mn2+) NADH Standard, 0.5 mole 1 vl and either the electron-accepting cofactor NADP+ (IDH1 Catalog Number MAK062G and IDH2) or NAD+ (IDH3) for their enzymatic activity. IDH1 and IDH2 mutations resulting in neomorphic Reagents and Equipment Required but Not enzymatic activity are found in certain cancers such as Provided. glioblastoma, acute myeloid leukemia, and colon 96 well flat-bottom plate – It is recommended to use cancer. This neoactivity shows a change in the clear plates for colorimetric assays. substrate specificity resulting in the conversion of Spectrophotometric multiwell plate reader -ketoglutarate to 2-hydroxyglutarate. Mutations in IDH family members are also associated with Ollier disease Precautions and Disclaimer and Maffucci syndrome. This product is for R&D use only, not for drug, household, or other uses. Please consult the Material The Isocitrate Dehydrogenase Activity Assay kit Safety Data Sheet for information regarding hazards provides a simple and direct procedure for measuring and safe handling practices. + + + NADP -dependent, NAD -dependent, or both NADP + and NAD -dependent IDH activity in a variety of Preparation Instructions samples. IDH activity is determined using isocitrate as Briefly centrifuge vials before opening. -
Isocitrate Dehydrogenase 1 (NADP+) (I5036)
Isocitrate Dehydrogenase 1 (NADP+), human recombinant, expressed in Escherichia coli Catalog Number I5036 Storage Temperature –20 °C CAS RN 9028-48-2 IDH1 and IDH2 have frequent genetic alterations in EC 1.1.1.42 acute myeloid leukemia4 and better understanding of Systematic name: Isocitrate:NADP+ oxidoreductase these mutations may lead to an improvement of (decarboxylating) individual cancer risk assessment.6 In addition other studies have shown loss of IDH1 in bladder cancer Synonyms: IDH1, cytosolic NADP(+)-dependent patients during tumor development suggesting this may isocitrate dehydrogenase, isocitrate:NADP+ be involved in tumor progression and metastasis.7 oxidoreductase (decarboxylating), Isocitric Dehydrogenase, ICD1, PICD, IDPC, ICDC, This product is lyophilized from a solution containing oxalosuccinate decarboxylase Tris-HCl, pH 8.0, with trehalose, ammonium sulfate, and DTT. Product Description Isocitrate dehydrogenase (NADP+) [EC 1.1.1.42] is a Purity: ³90% (SDS-PAGE) Krebs cycle enzyme, which converts isocitrate to a-ketoglutarate. The flow of isocitrate through the Specific activity: ³80 units/mg protein glyoxylate bypass is regulated by phosphorylation of isocitrate dehydrogenase, which competes for a Unit definition: 1 unit corresponds to the amount of 1 common substrate (isocitrate) with isocitrate lyase. enzyme, which converts 1 mmole of DL-isocitrate to The activity of the enzyme is dependent on the a-ketoglutarate per minute at pH 7.4 and 37 °C (NADP formation of a magnesium or manganese-isocitrate as cofactor). The activity is measured by observing the 2 complex. reduction of NADP to NADPH at 340 nm in the 7 presence of 4 mM DL-isocitrate and 2 mM MnSO4. -
(LCHAD) Deficiency / Mitochondrial Trifunctional Protein (MTF) Deficiency
Long chain acyl-CoA dehydrogenase (LCHAD) deficiency / Mitochondrial trifunctional protein (MTF) deficiency Contact details Introduction Regional Genetics Service Long chain acyl-CoA dehydrogenase (LCHAD) deficiency / mitochondrial trifunctional Levels 4-6, Barclay House protein (MTF) deficiency is an autosomal recessive disorder of mitochondrial beta- 37 Queen Square oxidation of fatty acids. The mitochondrial trifunctional protein is composed of 4 alpha London, WC1N 3BH and 4 beta subunits, which are encoded by the HADHA and HADHB genes, respectively. It is characterized by early-onset cardiomyopathy, hypoglycemia, T +44 (0) 20 7762 6888 neuropathy, and pigmentary retinopathy, and sudden death. There is also an infantile F +44 (0) 20 7813 8578 onset form with a hepatic Reye-like syndrome, and a late-adolescent onset form with primarily a skeletal myopathy. Tandem mass spectrometry of organic acids in urine, Samples required and carnitines in blood spots, allows the diagnosis to be unequivocally determined. An 5ml venous blood in plastic EDTA additional clinical complication can occur in the pregnant mothers of affected fetuses; bottles (>1ml from neonates) they may experience maternal acute fatty liver of pregnancy (AFLP) syndrome or Prenatal testing must be arranged hypertension/haemolysis, elevated liver enzymes and low platelets (HELLP) in advance, through a Clinical syndrome. Genetics department if possible. The genes encoding the HADHA and HADHB subunits are located on chromosome Amniotic fluid or CV samples 2p23.3. The pathogenic -
Is Glyceraldehyde-3-Phosphate Dehydrogenase a Central Redox Mediator?
1 Is glyceraldehyde-3-phosphate dehydrogenase a central redox mediator? 2 Grace Russell, David Veal, John T. Hancock* 3 Department of Applied Sciences, University of the West of England, Bristol, 4 UK. 5 *Correspondence: 6 Prof. John T. Hancock 7 Faculty of Health and Applied Sciences, 8 University of the West of England, Bristol, BS16 1QY, UK. 9 [email protected] 10 11 SHORT TITLE | Redox and GAPDH 12 13 ABSTRACT 14 D-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an immensely important 15 enzyme carrying out a vital step in glycolysis and is found in all living organisms. 16 Although there are several isoforms identified in many species, it is now recognized 17 that cytosolic GAPDH has numerous moonlighting roles and is found in a variety of 18 intracellular locations, but also is associated with external membranes and the 19 extracellular environment. The switch of GAPDH function, from what would be 20 considered as its main metabolic role, to its alternate activities, is often under the 21 influence of redox active compounds. Reactive oxygen species (ROS), such as 22 hydrogen peroxide, along with reactive nitrogen species (RNS), such as nitric oxide, 23 are produced by a variety of mechanisms in cells, including from metabolic 24 processes, with their accumulation in cells being dramatically increased under stress 25 conditions. Overall, such reactive compounds contribute to the redox signaling of the 26 cell. Commonly redox signaling leads to post-translational modification of proteins, 27 often on the thiol groups of cysteine residues. In GAPDH the active site cysteine can 28 be modified in a variety of ways, but of pertinence, can be altered by both ROS and 29 RNS, as well as hydrogen sulfide and glutathione. -
How Is Alcohol Metabolized by the Body?
Overview: How Is Alcohol Metabolized by the Body? Samir Zakhari, Ph.D. Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol-related tissue damage, and alcohol dependence. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver; interaction between alcohol metabolism byproducts and other cell components, resulting in the formation of harmful compounds (i.e., adducts); formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species [ROS]) that can damage other cell components; changes in the ratio of NADH to NAD+ (i.e., the cell’s redox state); tissue damage; fetal damage; impairment of other metabolic processes; cancer; and medication interactions. Several issues related to alcohol metabolism require further research. KEY WORDS: Ethanol-to acetaldehyde metabolism; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); acetaldehyde; acetate; cytochrome P450 2E1 (CYP2E1); catalase; reactive oxygen species (ROS); blood alcohol concentration (BAC); liver; stomach; brain; fetal alcohol effects; genetics and heredity; ethnic group; hypoxia The alcohol elimination rate varies state of liver cells. Chronic alcohol con- he effects of alcohol (i.e., ethanol) widely (i.e., three-fold) among individ- sumption and alcohol metabolism are on various tissues depend on its uals and is influenced by factors such as strongly linked to several pathological concentration in the blood T chronic alcohol consumption, diet, age, consequences and tissue damage. (blood alcohol concentration [BAC]) smoking, and time of day (Bennion and Understanding the balance of alcohol’s over time. -
Dehydrogenase Classes
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 4980-4984, May 1994 Biochemistry Fundamental molecular differences between alcohol dehydrogenase classes (Drosophila octano dehydrogenase/class m alcohol dehydrogenase/mo ur patterns/zinc enyme famy) OLLE DANIELSSON*, SILVIA ATRIANt, TERESA LUQUEt, LARS HJELMQVIST*, ROSER GONZALEZ-DUARTEt, AND HANS J6RNVALL*f *Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; tCenter for Biotechnology, Karolinska Institutet, S-141 86 Huddinge, Sweden; and tDepartment of Genetics, University of Barcelona, E-08071 Barcelona, Spain Communicated by Sune Bergstrom, January 18, 1994 ABSTRACT Two types of alcohol dehydrogenase in sepa- ary patterns, with class III being "constant" and class I rate protein families are the "medium-chain" zinc enzymes "variable" (10), result in a consistent picture of the enzyme (including the classical liver and yeast forms) and the "short- system and place the classes of medium-chain alcohol dehy- chain" enzymes (including the insect form). Although the drogenases as separate enzymes in the cellular metabolism. medium-chain family has been characterized in prokaryotes Similarly, another protein family, short-chain dehydroge- and many eukaryotes (fungi, plants, cephalopods, and verte- nases, has also evolved into a family comprising many brates), insects have seemed to possess only the short-chain different enzyme activities, including an alcohol dehydroge- enzyme. We have now also characterized a medium-chain nase (11). This form operates by means of a completely alcohol dehydrogenase in Drosophila. The enzyme is identical different catalytic mechanism and is related to mammalian to insect octanol dehydrogenase. It Is a typical class m alcohol prostaglandin dehydrogenases/carbonyl reductase (12). -
Moldx : BCKDHB Gene Test
Local Coverage Article: Billing and Coding: MolDX: BCKDHB Gene Test (A55099) Links in PDF documents are not guaranteed to work. To follow a web link, please use the MCD Website. Contractor Information CONTRACTOR NAME CONTRACT TYPE CONTRACT JURISDICTION STATE(S) NUMBER Noridian Healthcare Solutions, A and B MAC 01111 - MAC A J - E California - Entire State LLC Noridian Healthcare Solutions, A and B MAC 01112 - MAC B J - E California - Northern LLC Noridian Healthcare Solutions, A and B MAC 01182 - MAC B J - E California - Southern LLC Noridian Healthcare Solutions, A and B MAC 01211 - MAC A J - E American Samoa LLC Guam Hawaii Northern Mariana Islands Noridian Healthcare Solutions, A and B MAC 01212 - MAC B J - E American Samoa LLC Guam Hawaii Northern Mariana Islands Noridian Healthcare Solutions, A and B MAC 01311 - MAC A J - E Nevada LLC Noridian Healthcare Solutions, A and B MAC 01312 - MAC B J - E Nevada LLC Noridian Healthcare Solutions, A and B MAC 01911 - MAC A J - E American Samoa LLC California - Entire State Guam Hawaii Nevada Northern Mariana Islands Article Information General Information Article ID Original Effective Date Created on 12/19/2019. Page 1 of 6 A55099 10/17/2016 Article Title Revision Effective Date Billing and Coding: MolDX: BCKDHB Gene Test 12/01/2019 Article Type Revision Ending Date Billing and Coding N/A AMA CPT / ADA CDT / AHA NUBC Copyright Retirement Date Statement N/A CPT codes, descriptions and other data only are copyright 2018 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply. Current Dental Terminology © 2018 American Dental Association. -
HADHB Gene Hydroxyacyl-Coa Dehydrogenase Trifunctional Multienzyme Complex Subunit Beta
HADHB gene hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta Normal Function The HADHB gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. Mitochondrial trifunctional protein is made of eight parts (subunits). Four alpha subunits are produced from the HADHA gene, and four beta subunits are produced from the HADHB gene. As the name suggests, mitochondrial trifunctional protein contains three enzymes that each perform a different function. The beta subunits contain one of the enzymes, known as long-chain 3-keto- acyl-CoA thiolase. The alpha subunits contain the other two enzymes. These enzymes are essential for fatty acid oxidation, which is the multistep process that breaks down ( metabolizes) fats and converts them to energy. Mitochondrial trifunctional protein is required to metabolize a group of fats called long- chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils. These fatty acids are stored in the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues. Health Conditions Related to Genetic Changes Mitochondrial trifunctional protein deficiency Researchers have identified at least 26 mutations in the HADHB gene that cause mitochondrial trifunctional protein deficiency. These mutations reduce all three enzyme activities of mitochondrial trifunctional protein. Most mutations change one of the protein building blocks (amino acids) used to make the beta subunit. A change in amino acids probably alters the subunit's structure, which disrupts all three activities of the enzyme complex. -
Paroxysmal Spasticity of Lower Extremities As the Initial Symptom in Two Siblings with Maple Syrup Urine Disease
4872 MOLECULAR MEDICINE REPORTS 19: 4872-4880, 2019 Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease YI-DAN LIU1*, XU CHU2*, RUI-HUA LIU3, YING SUN1, QING-XIA KONG2 and QIU-BO LI3 1Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012; Departments of 2Neurology and 3Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China Received July 31, 2018; Accepted April 1, 2019 DOI: 10.3892/mmr.2019.10133 Abstract. Maple syrup urine disease (MSUD) is a rare heterozygous mutations in the BCKDHB gene found in the autosomal recessive metabolic disorder caused by muta- Chinese family may be responsible for the phenotype of the tions in genes that encode subunits of the branched-chain two siblings with MSUD. α-ketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation Introduction of branched-chain amino acids and their corresponding branched‑chain keto acids in the blood and cerebrospinal fluid, In the wide array of inherited metabolic disorders, maple which are neurovirulent and may become life-threatening. An syrup urine disease (MSUD; Online Mendelian Inheritance 11-day-old boy was admitted to the hospital with paroxysmal in Man no. 248600; https://www.omim.org/entry/248600) has spasticity of lower extremities. Of note, his 10-year-old sister attracted increasing attention due to the potential neurological presented similar symptoms during the neonatal period, and damage caused by this disorder (1). MSUD was first reported her condition was diagnosed as MSUD when she was 1.5 years by Menkes et al (2) in 1954. -
Two Novel HADHB Gene Mutations in a Korean Patient with Mitochondrial Trifunctional Protein Deficiency
Available online at www.annclinlabsci.org Annals of Clinical & Laboratory Science, vol. 39, no. 4, 2009 399 Case Report: Two Novel HADHB Gene Mutations in a Korean Patient with Mitochondrial Trifunctional Protein Deficiency Hyung-Doo Park,1,a Suk Ran Kim,1,a Chang-Seok Ki,1 Soo-Youn Lee,1 Yun Sil Chang,2 Dong-Kyu Jin,2 and Won Soon Park2 Departments of 1Laboratory Medicine & Genetics and 2Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea (aHyung-Doo Park and aSuk Ran Kim contributed equally to the work.) Abstract. Mitochondrial trifunctional protein (MTP) is a heterocomplex composed of 4 α-subunits containing LCEH (long-chain 2,3-enoyl-CoA hydratase) and LCHAD (long-chain 3-hydroxyacyl CoA dehydrogenase) activity, and 4 b-subunits that harbor LCKT (long-chain 3-ketoacyl-CoA thiolase) activity. MTP deficiency is an autosomal recessive disorder that causes a clinical spectrum of diseases ranging from severe infantile cardiomyopathy to mild chronic progressive polyneuropathy. Here, we report the case of a Korean male newborn who presented with severe lactic acidosis, seizures, and heart failure. A newborn screening test and plasma acylcarnitine profile analysis by tandem mass spectrometry showed an increase of 3-hydroxy species: 3-OH-palmitoylcarnitine, 0.44 nmol/ml (reference range, RR <0.07); 3-OH- linoleylcarnitine, 0.31 nmol/ml (RR <0.06); and 3-OH-oleylcarnitine, 0.51 nmol/ml (RR <0.04). These findings suggested either long-chain 3-hydroxyacyl-coA dehydrogenase deficiency or complete MTP deficiency. By molecular analysis of theHADHB gene, the patient was found to be a compound heterozygote for c.358dupT (p.A120CfsX8) and c.1364T>G (p.V455G) mutations. -
A Universal Tradeoff Between Growth and Lag in Fluctuating Environments
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nature. Manuscript Author Author manuscript; Manuscript Author available in PMC 2021 January 15. Published in final edited form as: Nature. 2020 August ; 584(7821): 470–474. doi:10.1038/s41586-020-2505-4. A universal tradeoff between growth and lag in fluctuating environments Markus Basan1,2,¶,*, Tomoya Honda3,4,*, Dimitris Christodoulou2, Manuel Hörl2, Yu-Fang Chang1, Emanuele Leoncini1, Avik Mukherjee1, Hiroyuki Okano3, Brian R. Taylor3, Josh M. Silverman5, Carlos Sanchez1, James R. Williamson5, Johan Paulsson1, Terence Hwa3,4,¶, Uwe Sauer2,¶ 1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. 2Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland. 3Department of Physics, University of California at San Diego, La Jolla, CA 92093 USA. 4Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093 USA. 5Department of Integrative Structural and Computational Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Abstract The rate of cell growth is crucial for bacterial fitness and a main driver of proteome allocation1,2, but it is unclear what ultimately determines growth rates in different environmental conditions. Increasing evidence suggests that other objectives also play key roles3–7, such as the rate of physiological adaptation to changing environments8,9. The challenge for cells is that these objectives often cannot be independently optimized, and maximizing one often reduces another. Many such tradeoffs have indeed been hypothesized, based on qualitative correlative studies8–11. Here we report the occurrence of a tradeoff between steady-state growth rate and physiological adaptability for Escherichia coli, upon abruptly shifting a growing culture from a preferred carbon source to fermentation products such as acetate. -
Carbonyl Stress in Bacteria: Causes and Consequences
ISSN 0006-2979, Biochemistry (Moscow), 2015, Vol. 80, No. 13, pp. 1655-1671. © Pleiades Publishing, Ltd., 2015. Original Russian Text © O. V. Kosmachevskaya, K. B. Shumaev, A. F. Topunov, 2015, published in Uspekhi Biologicheskoi Khimii, 2015, Vol. 55, pp. 49-82. REVIEW Carbonyl Stress in Bacteria: Causes and Consequences O. V. Kosmachevskaya, K. B. Shumaev, and A. F. Topunov* Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia; E-mail: [email protected] Received May 30, 2015 Abstract—Pathways of synthesis of the α-reactive carbonyl compound methylglyoxal (MG) in prokaryotes are described in this review. Accumulation of MG leads to development of carbonyl stress. Some pathways of MG formation are similar for both pro- and eukaryotes, but there are reactions specific for prokaryotes, e.g. the methylglyoxal synthase reaction. This reaction and the glyoxalase system constitute an alternative pathway of glucose catabolism – the MG shunt not associated with the synthesis of ATP. In violation of the regulation of metabolism, the cell uses MG shunt as well as other glycolysis shunting pathways and futile cycles enabling stabilization of its energetic status. MG was first examined as a biologically active metabolic factor participating in the formation of phenotypic polymorphism and hyperpersistent potential of bacte- rial populations. The study of carbonyl stress is interesting for evolutionary biology and can be useful for constructing high- ly effective producer strains. DOI: 10.1134/S0006297915130039 Key words: carbonyl stress, bacteria, methylglyoxal, metabolite overproduction The term “carbonyl stress” that describes an imbal- betes, which initiated studies of nonenzymatically glycat- ance between the formation and removal of reactive car- ed proteins and AGEs in living organisms.