MitoPedia: Inhibitors

From Bioblast
Revision as of 16:18, 10 February 2015 by Gnaiger Erich (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision β†’ (diff)

high-resolution terminology - matching measurements at high-resolution

MitoPedia: Inhibitors

The MitoPedia terminology is developed continuously in the spirit of Gentle Science.

Β»O2k-Publications: Inhibitor

2-Deoxyglucose2-DG2-Deoxyglucose, also known as 2-deoxy-D-glucose is a glucose derivative that has the 2-hydroxyl group replaced by hydrogen. It competitively inhibits glycolysis by blocking hexokinase and phosphohexoseisomerase.
2-mercaptoacetate2-mercaptoacetate is an inhibitor of medium-chain acyl-CoA dehydrogenase, MCAD, the rate-limiting enzyme of octanoylcarnitine oxidation. 2-mercaptoacetate has been used as an inhibitor of fatty acid oxidation (F-pathway control state). In permeabilized rat soleus muscle fibers, pre-incubation with 1 mM 2-mercaptoacetate for 45 min resulted in 58% inhibition of MCAD and decreased octanoylcarnitine&malate stimulated respiration by approximately 60% (Osiki 2016 FASEB J).
3-Mercaptopropionic acidMPA3-Mercaptopropionic acid (MPA) inhibits long chain acyl-CoA dehydrogenases (ACADs).
AmytalAmyAmytal sodium salt (synonym: amobarbital; 5-Ethyl-5-isoamylbarbituric acid) is a barbiturate drug and an inhibitor of Complex I.
Antimycin AAmaAntimycin A is an inhibitor of Complex III (CIII). It binds to the Qi site of CIII and inhibits the transfer of electrons from heme bH to oxidized Q (Qi site inhibitor). High concentrations of antimycin A also inhibit acyl-CoA oxidase and D-amino acid oxidase.
Ap5AAp5AP1,P5-Di(adenosine-5')pentaphosphate (Ap5A) is an inhibitor of adenylate kinase (ADK), the enzyme which rephosphorylates AMP to ADP, consuming ATP (ATP + AMP ↔ 2 ADP).
AtractylosideAtrAtractyloside is an inhibitor of the adenine nucleotide translocator (ANT). It is an extremely toxic glycoside that inhibits oxidative phosphorylation by blocking the transfer of adenosine nucleotides through the mitochondrial membrane.
AuranofinAFAuranofin (AF) is a gold complex which inhibites thioredoxin reductase (TrxR).
AzideAzdSodium azide is an inhibitor of Complex IV/cytochrome c oxidase (CIV, COX, CcO).
Beryllium sulfateBeSBeryllium sulfate is used in combination with sodium fluoride to form beryllium trifluoride (BeF3βˆ’), to inhibit the ATP synthase if it is exposed by disruption of the mitochondrial membranes.
BlebbistatinBlebBlebbistatin is a widely used muscle and non-muscle myosin II-specific inhibitor that block contractile activity. Blebbistatin shows selectivity and high affinity for multiple class II myosins. Blebbistatin is commonly employed in respirometric experiments with permeabilized muscle fibers (pfi). Permeabilized muscle fibers are sensitive to low oxygen supply due to diffusion restrictions that limit mitochondrial respiration at the core of the fiber bundle. Therefore, hyperoxic conditions are required to counteract this limitation. Further studies have shown that the addition of blebbistatin in the respiration medium prevents fiber contraction, reduces the oxygen sensitivity and allows the study of ADP kinetics in pfi at normoxic oxygen levels. However, other studies described that the presence of blebbistatin does not prevent the oxygen dependence in pfi. Moreover, several limitations of blebbistatin i.e. low solubility in water, cytotoxicity and phototoxicity have been described.
Bongkrekik acidBkaBongkrekik acid is a selective and potent inhibitor of the adenine nucleotide translocator (ANT). Bka binds to the matrix (negative) site of ANT, opposite of carboxyatractyloside.
CarboxyatractylosideCATCarboxyatractyloside CAT is a highly selective and potent inhibitor of the adenine nucleotide translocator (ANT). CAT stabilizes the nucleoside binding site of ANT on the cytoplasmic (positive) side of the inner membrane and blocks the exchange of matrix ATP and cytoplasmic ADP. It causes stabilization of the c conformation of ANT leading to permeability transition pore (PTP) opening, loss of mitochondrial membrane potential, and apoptosis.
CitreoviridinCitreoviridin is an inhibitor of the ATP synthase which, differently from the FO subunit binding inhibitor oligmycin, binds to the F1 subunit of the ATP synthase.
CyanideKCNCyanide (usually added as KCN) is a competitive inhibitor of cytochcrome c oxidase (CIV). Inhibition is reversed by pyruvate and high oxygen levels.
Cyclosporin ACsACyclosporin A (CsA) is a cyclic undecapeptide from an extract of soil fungi that binds the cyclophilin D and thus preventing the formation of the mitochondrial permeability transition pore. The interaction of CsA with the cyclophilin D is phosphate mediated but the full mechanism of interaction is not well understood. For example, the deficiency of cyclophilin D in KO models does not prevent mitochondria from permeability transition and from CsA inhibition. Moreover, it is also a is a calcineurin inhibitor and potent immunosuppressive agent used largely as a means of prophylaxis against cellular rejection after solid organ transplantation.
DinitrochlorobenzeneDNCBDinitrochlorobenzene (1-chloro-2,4-dinitrobenzene) (DNCB) is a glutathione (GSH) inhibitor.
Ethanolethanol abs.
Ethanol or ethyl alcohol, C2H6O or EtOH, is widely used in the laboratory, particularly as a solvent and cleaning agent. There are different grades of high purity ethanol. Up to a purity of 95.6 % ethanol can be separated from water by destillation. Higher concentrations than 95% require usage of additives that disrupt the azeotrope composition and allow further distillation. Ethanol is qualified as "absolute" if it contains no more than one percent water. Whenever 'ethanol abs.' is mentioned without further specification in published protocols, it refers to β‰₯ 99 % ethanol a.r. (analytical reagent grade).
EtomoxirEtoEtomoxir (Eto; 2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate) is an irreversible inhibitor of carnitine palmitoyltransferase I (CPT-I) on the outer face of the mitochondrial inner membrane. Eto inhibits fatty acid oxidation by blocking the formation of acyl carnitines from long-chain fatty acids which require the carnitine shuttle for transport into mitochondria. In contrast to long-chain fatty acids, the transport of short- and medium-chain fatty acids is carnitine-independent.
HydroxycinnamateHciHydroxycinnamate (alpha-cyano-4-hydroxycinnamic acid) is an inhibitor of the pyruvate carrier (0.65 mM). Above 10 mM pyruvate, hydroxycinnamate cannot inhibit respiration from pyruvate, since the weak pyruvic acid can pass the inner mt-membrane in non-dissociated form.
HydroxylamineHydroxylamine is an inhibitor of catalase.
MalonateMnaMalonate (malonic acid) is a competitive inhibitor of succinate dehydrogenase (Complex II). Malonate is a substrate of malonyl-CoA synthase.
MersalylMersalyl (C13H17HgNO6) is an inhibitor of the Pi symporter.
Metabolic control variableXA metabolic control variable X causes the transition between a background state Y (background rate YX) and a reference state Z (reference rate ZX). X may be a stimulator or activator of flux, inducing the step change from background to reference steady state (Y to Z). Alternatively, X may be an inhibitor of flux, absent in the reference state but present in the background state (step change from Z to Y).
Cell permeable prodrugs, composed of MitoKit-CII/Succinate-nv and MitoKit-CII/Malonate-nv, stimulates (Snv) or inhibits (Mnanv) mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres, acting on Complex II of the electron transfer system.
MitoKit-CII/Malonate-nvMnanvMitoKit-CII/Malonate-nv (diacetoxymethyl malonate) is a plasma membrane-permeable prodrug (permeable malonate; Mnanv) that diffuses across the plasma membrane. Cleavage of diacetoxymethyl groups is mediated by intracellular esterases, thus releasing malonate in the intracellular space. Abliva #: 01-161-s2
MitoKit-CII/Succinate-nvSnvMitoKit-CII/Succinate-nv (diacetoxymethyl succinate) is a plasma membrane-permeable prodrug (permeable succinate; Snv) that diffuses across the plasma membrane. Cleavage of diacetoxymethyl groups is mediated by intracellular esterases, thus releasing succinate in the intracellular space. Abliva #: 01-118-s4
MyxothiazolMyxMyxothiazol Myx is an inhibitor of Complex III (CIII). CIII also inhibits CI. Myxothiazol binds to the Qo site of CIII (close to cytochrome bL) and inhibits the transfer of electrons from reduced QH2 to the Rieske iron sulfur protein.
N-ethylmaleimideNemN-ethylmaleimide is an organic compound that is derived from maleic acid and blocks endogenous Pi transport.
OligomycinOmyOligomycin (Omy) is an inhibitor of ATP synthase by blocking its proton channel (Fo subunit), which is necessary for oxidative phosphorylation of ADP to ATP (energy production). The inhibition of ATP synthesis also inhibits respiration. In OXPHOS analysis, Omy is used to induce a LEAK respiration state of respiration (abbreviated as L(Omy) to differentiate from L(n), LEAK state in the absence of ADP).
OuabainOuaOuabain (synonym: G-strophantin octahydrate) is a poisonous cardiac glycoside. The classical mechanism of action of ouabain involves its binding to and inhibition of the plasma membrane Na+/K+-ATPase (sodium pump) especially at the higher concentrations. Low (nanomolar and subnanomolar) concentrations of ouabain stimulate the Na-K-ATPase.
Oxalomalic acidOxalomalic acid is an inhibitor of aconitase (and of cytoplasmic NADP-dependent isocitrate dehydrogenase). Aconitase mediates the isomerization of citrate to isocitrate as the first step in the TCA cycle. Oxalomalic acid has been used at 1 mM concentration and after 45 min of pre-incubation to inhibit aconitase in permeabilized rat Soleus muscle fibres, inhibiting the enzyme by 24% (Osiki 2016 FASEB J).
PhenylsuccinatePhenylsuccinate is a competitive inhibitor of succinate transport (20 mM).
PiericidinPiericidin C25H37NO4 is an antibiotic (isolated from Streptomyces mobaraensis) showing similarity with ubiquinone structure which has a potent and competitive inhibitory effect of CI (it competes with endogenous and partially with exogenous Q for binding sites). CI inhibitors have been divided (1) depending of the site of action (functional classification): quinone antagonists (e.g. piericidin A, first site), semiquinone antagonists (piericidin A, second site; piericidin B; rotenone and quinol antagonists (myxothiazol; stigmatellin), and (2) depending on their effect on ROS production: inducing ROS production (e.g. rotenone, piericidin A, Rolliniastatin-1 and -2) and preventing ROS production (e.g. stigmatellin, capsaicin, mucidin and coenzyme Q2). In plants, pieridicin A inhibits photosystem II.
Preparation of SUIT chemicalsPreparation of SUIT chemicals describes the preparation of chemicals used in Substrate-Uncoupler-Inhibitor Ttitration (SUIT) protocols.
RotenoneRotRotenone is an inhibitor of Complex I (CI) and thus inhibits NADH oxidation. It inhibits the transfer of electrons from iron-sulfur clusters in CI to ubiquinone via binding to the ubiquinone binding site of CI. See also Succinate pathway.
Ruthenium redRRRuthenium red (synonym: ammoniated ruthenium oxychloride) inhibits the mitochondrial Ca2+ uniporter. However, in addition it has been shown to interact with and inhibit a large number of other proteins, including ion channels particularly of the Transient Receptor Potential Vanilloid (TRPV) family [1], Ca2+-ATPases, and, importantly, the voltage-dependent anion channel (VDAC) [2].
Salicylhydroxamic acidSHAMSalicylhydroxamic acid (SHAM; synonym: 2-Hydroxybenzohydroxamic acid N,2-Dihydroxybenzamide) is an inhibitor of the alternative oxidase (AOX). When AOX is blocked by SHAM, electrons are forced through the CIII-cytochrome c oxidase pathway, allowing observation of the operation of the CIII-CIV pathway without AOX activity.
Sodium fluorideNaFSodium fluoride (NaF) is used in combination with beryllium sulfate to form beryllium trifluoride (BeF3βˆ’), to inhibit the ATP synthase if it is exposed by disruption of the mitochondrial membranes.
Sodium orthovanadateVO4Sodium vanadate (Na3VO4) is used as an ATPase inhibitor.
StrobilurinStrobilurin: {Quote} Strobilurins are a group of chemical compounds used in agriculture as fungicides. They are part of the larger group of QoI inhibitors, which act to inhibit {end of Quote: [1]} respiratory Complex III.
Substrate-uncoupler-inhibitor titrationSUITMitochondrial Substrate-uncoupler-inhibitor titration (SUIT) protocols are used with mitochondrial preparations to study respiratory control in a sequence of coupling and substrates states induced by multiple titrations within a single experimental assay.
TPP+ inhibitory effectA major task in establishing a procedure for measurement of mitochondrial membrane potential using probe molecules is the evaluation of inhibitory concentrations of the probe molecule on the activity of respiration. The TPP+ inhibitory effect (this also applies to TPMP+ and other indicator molecules) is frequently ignored. Accurate knowledge of a threshold concentration is required to evaluate the necessary limit of detection of TPP+, and for restriction of experimental TPP+ concentrations below the inhibitory range.
Tartronic acidTartronic acid (hydroxymalonic acid, C3H4O5; molecular weight 120.06) is an inhibitor of malic enzyme.
ThenoyltrifluoroacetoneTTFAThenoyltrifluoroacetone TTFA is a noncompetitive inhibitor of CII binding on the quinone-binding (SDHC/SDHD).
Triethyltin bromideTETTriethyltin bromide (TET) is a lipophilic [1] inhibitor of the mitochondrial ATP synthase [2] which is used to induce LEAK state in living cells of Saccharomyces cerevisiae.
Volume of the soluteMost of the chemicals for SUIT protocol titrations are prepared by weighing the substance on the balance, transferring to a volumetric glass flask and adding solvent until the intended volume is reached. However, for practical reasons some of the chemical compounds are prepared by just adding the solvent instead of adjusting it's volume. For example, this approach is useful if the substance is very toxic. Then an arbitratry amount is taken, its mass determined on the balance without trying to reach a specific value and the necessary amount of solvent is added. Adding the solvent instead of adjusting its volume is also useful if small amounts are needed (e.g. 1 mL) or if the compound has to be prepared directly before using it like Pyruvate. In these cases the volume contributed by the solute was tested.
Cookies help us deliver our services. By using our services, you agree to our use of cookies.