Glutathione Peroxidase
An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9.
Peroxidases
Peroxidases are enzymes that catalyze the reduction of hydrogen peroxide to water, while oxidizing various organic and inorganic compounds, playing crucial roles in diverse biological processes including stress response, immune defense, and biosynthetic reactions.
Glutathione
Selenium
An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of GLUTATHIONE PEROXIDASE.
Glutathione Transferase
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
Glutathione Reductase
Catalyzes the oxidation of GLUTATHIONE to GLUTATHIONE DISULFIDE in the presence of NADP+. Deficiency in the enzyme is associated with HEMOLYTIC ANEMIA. Formerly listed as EC 1.6.4.2.
Horseradish Peroxidase
Catalase
An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.
Superoxide Dismutase
An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1.
Antioxidants
Glutathione Disulfide
A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.
Oxidative Stress
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Peroxidase
Lipid Peroxidation
Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.
Selenoproteins
Selenoproteins are proteins that specifically incorporate SELENOCYSTEINE into their amino acid chain. Most selenoproteins are enzymes with the selenocysteine residues being responsible for their catalytic functions.
Hydrogen Peroxide
Selenious Acid
Cytochrome-c Peroxidase
A hemeprotein which catalyzes the oxidation of ferrocytochrome c to ferricytochrome c in the presence of hydrogen peroxide. EC 1.11.1.5.
Selenoprotein P
An extracellular selenoprotein that contains most of the SELENIUM in PLASMA. Selenoprotein P functions as an antioxidant and appears to transport selenium from the LIVER to peripheral tissues.
Ascorbate Peroxidases
Peroxidases that utilize ASCORBIC ACID as an electron donor to reduce HYDROGEN PEROXIDE to WATER. The reaction results in the production of monodehydroascorbic acid and DEHYDROASCORBIC ACID.
Thiobarbituric Acid Reactive Substances
Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct.
Lipid Peroxides
Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.
Oxidation-Reduction
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Selenocysteine
A naturally occurring amino acid in both eukaryotic and prokaryotic organisms. It is found in tRNAs and in the catalytic site of some enzymes. The genes for glutathione peroxidase and formate dehydrogenase contain the TGA codon, which codes for this amino acid.
Glutathione Synthase
One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of glutathione from gamma-glutamylcysteine and glycine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.3.
Iodide Peroxidase
A hemeprotein that catalyzes the oxidation of the iodide radical to iodine with the subsequent iodination of many organic compounds, particularly proteins. EC 1.11.1.8.
Peroxides
A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Liver
Eosinophil Peroxidase
A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity.
Erythrocytes
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Sodium Selenite
The disodium salt of selenious acid. It is used therapeutically to supply the trace element selenium and is prepared by the reaction of SELENIUM DIOXIDE with SODIUM HYDROXIDE.
Reactive Oxygen Species
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Buthionine Sulfoximine
A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7)
Peroxiredoxins
A family of ubiquitously-expressed peroxidases that play a role in the reduction of a broad spectrum of PEROXIDES like HYDROGEN PEROXIDE; LIPID PEROXIDES and peroxinitrite. They are found in a wide range of organisms, such as BACTERIA; PLANTS; and MAMMALS. The enzyme requires the presence of a thiol-containing intermediate such as THIOREDOXIN as a reducing cofactor.
Vitamin E
A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.
tert-Butylhydroperoxide
Organoselenium Compounds
Organic compounds which contain selenium as an integral part of the molecule.
Glutamate-Cysteine Ligase
Ascorbic Acid
A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.
Glutathione S-Transferase pi
A glutathione transferase that catalyzes the conjugation of electrophilic substrates to GLUTATHIONE. This enzyme has been shown to provide cellular protection against redox-mediated damage by FREE RADICALS.
Dinitrochlorobenzene
Free Radicals
Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.
Thioredoxin-Disulfide Reductase
A FLAVOPROTEIN enzyme that catalyzes the oxidation of THIOREDOXINS to thioredoxin disulfide in the presence of NADP+. It was formerly listed as EC 1.6.4.5
Rats, Wistar
Selenium Compounds
Inorganic compounds that contain selenium as an integral part of the molecule.
Diquat
Oxidants
Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).
Thiomalates
Isoenzymes
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Oxidoreductases
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
Vitamin E Deficiency
A nutritional condition produced by a deficiency of VITAMIN E in the diet, characterized by posterior column and spinocerebellar tract abnormalities, areflexia, ophthalmoplegia, and disturbances of gait, proprioception, and vibration. In premature infants vitamin E deficiency is associated with hemolytic anemia, thrombocytosis, edema, intraventricular hemorrhage, and increasing risk of retrolental fibroplasia and bronchopulmonary dysplasia. An apparent inborn error of vitamin E metabolism, named familial isolated vitamin E deficiency, has recently been identified. (Cecil Textbook of Medicine, 19th ed, p1181)
Benzene Derivatives
Peroxiredoxin VI
A peroxiredoxin that is a cytosolic bifunctional enzyme. It functions as a peroxiredoxin via a single redox-active cysteine and also contains a Ca2+-independent acidic phospholipase A2 activity.
Free Radical Scavengers
Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries.
Cysteine
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
Selenic Acid
A strong dibasic acid with the molecular formula H2SeO4. Included under this heading is the acid form, and inorganic salts of dihydrogen selenium tetraoxide.
Plant Extracts
Paraquat
Guaiacol
Amitrole
A non-selective post-emergence, translocated herbicide. According to the Seventh Annual Report on Carcinogens (PB95-109781, 1994) this substance may reasonably be anticipated to be a carcinogen. (From Merck Index, 12th ed) It is an irreversible inhibitor of CATALASE, and thus impairs activity of peroxisomes.
Peroxiredoxin III
A THIOREDOXIN-dependent hydroperoxidase that is localized in the mitochondrial matrix. The enzyme plays a crucial role in protecting mitochondrial components from elevated levels of HYDROGEN PEROXIDE.
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Amino Acid Sequence
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Gene Expression Regulation, Enzymologic
Acetylcysteine
Protein Carbonylation
The appearance of carbonyl groups (such as aldehyde or ketone groups) in PROTEINS as the result of several oxidative modification reactions. It is a standard marker for OXIDATIVE STRESS. Carbonylated proteins tend to be more hydrophobic and resistant to proteolysis.
Cytosol
Selenoprotein W
A single SELENOCYSTEINE containing protein that binds reduced GLUTATHIONE and can act as an antioxidant.
Methionine Sulfoximine
Thioredoxins
Hydrogen-donating proteins that participates in a variety of biochemical reactions including ribonucleotide reduction and reduction of PEROXIREDOXINS. Thioredoxin is oxidized from a dithiol to a disulfide when acting as a reducing cofactor. The disulfide form is then reduced by NADPH in a reaction catalyzed by THIOREDOXIN REDUCTASE.
Aurothioglucose
Glutaredoxins
A family of thioltransferases that contain two active site CYSTEINE residues, which either form a disulfide (oxidized form) or a dithiol (reduced form). They function as an electron carrier in the GLUTHIONE-dependent synthesis of deoxyribonucleotides by RIBONUCLEOTIDE REDUCTASES and may play a role in the deglutathionylation of protein thiols. The oxidized forms of glutaredoxins are directly reduced by the GLUTATHIONE.
Glucosephosphate Dehydrogenase
Glucose-6-Phosphate Dehydrogenase (G6PD) is an enzyme that plays a critical role in the pentose phosphate pathway, catalyzing the oxidation of glucose-6-phosphate to 6-phosphoglucono-δ-lactone while reducing nicotinamide adenine dinucleotide phosphate (NADP+) to nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), thereby protecting cells from oxidative damage and maintaining redox balance.
Rats, Sprague-Dawley
White Muscle Disease
A myodegeneration most frequent in calves and lambs whose dams have been fed during gestation or longer on feeds, especially legumes (FABACEAE), grown in certain areas where selenium is either deficient or unavailable in the soil. It has been recorded in many countries. It has been produced experimentally in several species of animals on low-selenium intake. A similar myopathy occurs naturally in goats, deer, foals, and dogs but proof of the etiology is lacking. (Merck Veterinary Manual, 5th ed)
Selenium Oxides
Inorganic compounds formed through the oxidation of selenium.
Substrate Specificity
Lactoperoxidase
Base Sequence
Thioredoxin Reductase 1
A subtype of thioredoxin reductase found primarily in the CYTOSOL.
Selenium Radioisotopes
NADP
Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)
gamma-Glutamyltransferase
An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.
Rats, Inbred Strains
Chromatography, High Pressure Liquid
Enzyme Induction
Kidney
Dose-Response Relationship, Drug
alpha-Tocopherol
A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.
Selenium-Binding Proteins
Lignin
The most abundant natural aromatic organic polymer found in all vascular plants. Lignin together with cellulose and hemicellulose are the major cell wall components of the fibers of all wood and grass species. Lignin is composed of coniferyl, p-coumaryl, and sinapyl alcohols in varying ratios in different plant species. (From Merck Index, 11th ed)
Catalysis
Cells, Cultured
Cell Survival
Oxygen
Mitochondria
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Thiobarbiturates
Cystine
Random Allocation
Drug-Induced Liver Injury
Maleates
Cloning, Molecular
Protective Agents
Proteins
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Superoxides
Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.
Basidiomycota
Xanthine Oxidase
An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria.
Blotting, Western
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Cattle
Metabolic Detoxication, Drug
Chloride Peroxidase
Dietary Supplements
Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.
Acatalasia
A rare autosomal recessive disorder resulting from the absence of CATALASE activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present.
Diamide
Body Weight
Epididymis
The convoluted cordlike structure attached to the posterior of the TESTIS. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of SPERMATOZOA.
Herbicides
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Thioredoxin Reductase 2
A subtype of thioredoxin reductase found primarily in MITOCHONDRIA.
Glucose Oxidase
An enzyme of the oxidoreductase class that catalyzes the conversion of beta-D-glucose and oxygen to D-glucono-1,5-lactone and peroxide. It is a flavoprotein, highly specific for beta-D-glucose. The enzyme is produced by Penicillium notatum and other fungi and has antibacterial activity in the presence of glucose and oxygen. It is used to estimate glucose concentration in blood or urine samples through the formation of colored dyes by the hydrogen peroxide produced in the reaction. (From Enzyme Nomenclature, 1992) EC 1.1.3.4.
Aspartate Aminotransferases
Benzyl Alcohols
Myocardium
Sequence Homology, Amino Acid
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Tissue Distribution
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
Mice, Inbred C57BL
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
DNA, Complementary
Heme
NF-E2-Related Factor 2
Testis
Biological Markers
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Gene Expression
Aging
Isoprostanes
A series of prostaglandin-like compounds that are produced by the attack of free-radical species on unsaturated fatty acids, especially ARACHIDONIC ACID, of cellular MEMBRANES. Once cleaved from the lipid membrane by the action of phospholipases they can circulate into various bodily fluids and eventually be excreted. Although these compounds resemble enzymatically synthesized prostaglandins their stereoisometric arrangement is usually different than the "naturally occurring" compounds.
Binding Sites
Alloxan
Electrophoresis, Polyacrylamide Gel
Cytoprotection
gamma-Butyrobetaine Dioxygenase
An enzyme that catalyzes the HYDROXYLATION of gamma-butyrobetaine to L-CARNITINE. It is the last enzyme in the biosynthetic pathway of L-CARNITINE and is dependent on alpha-ketoglutarate; IRON; ASCORBIC ACID; and OXYGEN.
Copper
Dithiothreitol
Lung
Hydrogen-Ion Concentration
Disease Models, Animal
Acetaminophen
Alanine Transaminase
L-Lactate Dehydrogenase
Antibodies, Catalytic
Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.
Nitric Oxide
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
Enzymes
Trace Elements
Cadmium
An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.
Enzyme Activation
Drugs, Chinese Herbal
Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.
Blotting, Northern
Spermatozoa
Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility.
Drug Resistance
Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
Spectrophotometry
Tumor Cells, Cultured
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.