Semantic search

This page or action requires Javascript to work, please enable Javascript in your browser or use a browser where this is supported so that functionality can be served and is provided as requested. For further assistance, please have a look at the noscript help page.

Search Clear all entries

Term	Abbreviation	Description
Inorganic phosphate	P_i	Inorgnic phosphate (P_i) is a salt of phosphoric acid. In solution near physiological pH, the species HPO₄^2- and H₂PO₄^- dominate. See also: Phosphate carrier (Pic).
Isocitrate		isocitrate, C₆H₅O₇^-3, is a tricarboxylic acid trianion, intermediate of the TCA cycle, obtained by isomerization of citrate. The process is catalyzed by aconitase, forming the enzyme-bound intermediate cis-aconitate.
Jmax	J_max	J_max is the maximum pathway flux (e.g. oxygen flux) obtained at saturating substrate concentration. J_max is a function of metabolic state. In hyperbolic ADP or oxygen kinetics, J_max is calculated by extrapolation of the hyperbolic function, with good agreement between the calculated and directly measured fluxes, when substrate levels are >20 times the c₅₀ or p₅₀.
Malate	M	Malic acid, C₄H₆O₅, occurs under physiological conditions as the anion malate^2-, M, with pK_a1 = 3.40 and pK_a2 = 5.20. L-Malate is formed from fumarate in the TCA cycle in the mitochondrial matrix, where it is the substrate of malate dehydrogenase oxidized to oxaloacetate. Malate is also formed in the cytosol. It cannot permeate through the lipid bilayer of membranes and hence requires a carrier (dicarboxylate carrier, tricarboxylate carrier and 2-oxoglutarate carrier). Malate alone cannot support respiration of mt-preparations from most tissues, since oxaloacetate accumulates in the absence of pyruvate or glutamate. Malate is a type N substrate (N) required for the FAO-pathway. In the presence of anaplerotic pathways (e.g., mitochondrial malic enzyme, mtME) the capacity of the FAO-pathway can be overestimated due to a contribution of NADH-linked respiration, F(N) (see SUIT-002).
Malate transport		Carriers for malate: dicarboxylate carrier tricarboxylate carrier 2-oxoglutarate carrier
Metabolic control variable	X	A metabolic control variable X causes the transition between a background state Y (background rate Y_X) and a reference state Z (reference rate Z_X). 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).
Methylmalonic acid	Mma	Methylmalonic acid (Mma) is a common intermediate in many catabolic processes. In methylmalonic acidemia mitochondrial dysfunction can be observed, related to accumulation of Mma and associated with neurological symptoms.
MitoKit-CII		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.
NADH	NADH	NAD⁺ and NADH: see Nicotinamide adenine dinucleotide.
NS-pathway control state	NS, CI&II	NS-pathway control is exerted in the NS-linked substrate state (flux in the NS-linked substrate state, NS; or Complex I&II, CI&II-linked substrate state). NS-OXPHOS capacity provides an estimate of physiologically relevant maximum mitochondrial respiratory capacity. NS is induced in mt-preparations by addition of NADH-generating substrates (N-pathway control state in combination with succinate (Succinate pathway; S). Whereas NS expresses substrate control in terms of substrate types (N and S), CI&II defines the same concept in terms of convergent electron transfer to the Q-junction (pathway control). NS is the abbreviation for the combination of NADH-linked substrates (N) and succinate (S). This physiological substrate combination is required for partial reconstitution of TCA cycle function and convergent electron-input into the Q-junction, to compensate for metabolite depletion into the incubation medium. NS in combination exerts an additive effect of convergent electron flow in most types of mitochondria.
Nicotinamide adenine dinucleotide	NADH	Nicotinamide adenine dinucleotide, NAD⁺ and NADH (pyridine nucleotide coenzymes, NAD and NADP), is an oxidation-reduction coenzyme (redox cofactor; compare FADH₂). In the NADH electron transfer-pathway state fuelled by type N-substrates, mt-matrix dehydrogenases generate NADH, the substrate of Complex I (CI). The reduced N-substrate RH₂ is oxidized and NAD⁺ is reduced to NADH,:::: RH₂ + NAD⁺ → NADH + H⁺ + RThe mt-NADH pool integrates the activity of the TCA cycle and various matrix dehydrogenases upstream of CI, and thus forms a junction or funnel of electron transfer to CI, the N-junction (compare F-junction, Q-junction). NAD⁺ and NADH are not permeable through the mt-inner membrane, mtIM. Therefore, an increase of mitochondrial respiration after the addition of NADH may indicate an alteration of the mtIM integrity. Cytosolic NADH is effectively made available for mitochondrial respiration through the malate-aspartate shuttle or glycerophosphate dehydrogenase Complex.
Octanoate	Oca	Octanoate (octanoic acid). C₈H₁₆O₂ Common name: Caprylic acid.
Octanoylcarnitine	Oct	Octanoylcarnitine is a medium-chain fatty acid (octanoic acid: eight-carbon saturated fatty acid) covalently linked to carnitine, frequently applied as a substrate for fatty acid oxidation (FAO) in mitochondrial preparations.
Oxaloacetate	Oa	Oxaloacetic acid, C₄H₄O₅, occurs under physiological conditions as the anion oxaloacetate^2-, Oa. Oxaloacetate is formed from malate by MDH. Oa reacts with acetyl-CoA through citrate synthase to form citrate, or with glutamate through transaminase to form oxoglutarate and aspartate. Oa transport is restricted across the inner mt-membrane of various tissues. Oa is a potent inhibitor of succinate dehydrogenase.
Oxoglutarate	Og	2-Oxoglutaric acid or alpha-ketoglutaric acid, C₅H₆O₅, occurs under physiological conditions as the anion 2-Oxoglutarate^2-, Og. 2-Oxoglutarate (alpha-ketoglutarate) is formed from isocitrate as a product of isocitrate dehydrogenase (IDH) in the TCA cycle, and is a substrate of oxoglutarate dehydrogenase (OgDH). The 2-oxoglutarate carrier exchanges malate^2- for 2-oxoglutarate^2- as part of the malate-aspartate shuttle. In the cytosol, oxoglutarate+aspartate are transaminated to form oxaloacetate+glutamate. Cytosolic malate dehydrogenase converts oxaloacetate+NADH to malate.
Oxygen	O₂	Molecular oxygen, O₂ or dioxygen, has two atoms of oxygen, O, which is the chemical element with atomic number 8. The relative molecular mass of O₂, M_r,O2, is 32 (or 31.9988). The element O has 8 protons, 8 neutrons and 8 electrons. In the figure, the two electrons in the first electron shell are not shown. Of the six electrons in the outer shell (blue bullets), one electron from each of the two atoms is shared in O₂ forming the covalent bond, and one electron in each atom is unpaired.
P50	p₅₀	p₅₀ is the oxygen partial pressure at which (a) respiratory flux is 50% of maximum oxygen flux, J_max, at saturating oxygen levels. The oxygen affinity is indirectly proportional to the p₅₀. The p₅₀ depends on metabolic state and rate. (b) p₅₀ is the oxygen partial pressure at which oxygen binding (on myoglobin, haemoglobin) is 50%, or desaturation is 50%.
Palmitate	Paa	Palmitate is a term for the salts and esters of palmitic acid (CH₃(CH₂)₁₄COOH). Palmitic acid is the first fatty acid produced during fatty acid synthesis and the precursor to longer fatty acids. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC), which is responsible for converting acetyl-CoA to malonyl-CoA, which in turn is used to add to the growing acyl chain, thus preventing further palmitate generation. In order to dissolve the water-insoluble sodium palmitate, BSA is needed to form the water-soluble compound called palmitate:BSA.
Palmitoyl-CoA	Pa-CoA	Palmitoyl-CoA is a coenzyme A derivative of palmitate formed by acyl-CoA synthase. In contrast to medium- and short-chain acyl-CoA, palmitoyl-CoA cannot freely diffuse into the mitochondrial matrix. Formation of palmitoylcarnitine by CPTI is necessary prior to transfer into mitochondria for further fatty acid oxidation (β-oxidation). To study Fatty acid oxidation using Palmitoyl-CoA, Carnitine and low amount of malate is needed on mitochondrial preparations.
Palmitoylcarnitine	Pal	Palmitoylcarnitine is an ester derivative of carnitine (long-chain acylcarnitine) involved in the metabolism of fatty acids. Within the cell, palmitoylcarnitine is transported into the mitochondria to deliver palmitate for fatty acid oxidation and energy production.
Phosphate	P_i	See: Inorganic phosphate
Phosphocreatine	PCr	Phosphocreatine is a high energy compound in the skeletal muscle of vertebrates and is present in 4 to 5 times the concentration of ATP.
Preparation of SUIT chemicals		Preparation of SUIT chemicals describes the preparation of chemicals used in Substrate-Uncoupler-Inhibitor Ttitration (SUIT) protocols.
Product		A product in a chemical reaction has a positive stoichiometric number since it is produced, whereas a substrate has a negative stoichiometric number since it is consumed.
Proline	Pro	Proline (Pro), C₅H₉NO₂, is an amino acid which occurs under physiological conditions mainly in the nonpolar form, with pK_a1 = 1.99 pK_a2 = 10.96. Proline is an anaplerotic substrate that supports both the proline pathway control state and the glutamate-anaplerotic pathway control state. Proline is used as a single substrate or in combination with carbohydrate-derived metabolites in mitochondria particularly of flight muscle of many (but not all) insects. Proline is oxidized to delta-1-pyrroline-5-carboxylate by the mtIM L-proline:quinone oxidoreductase (proline dehydrogenase, ProDH), with reduction of FAD to FADH₂ and direct entry into the Q-junction. delta-1-pyrroline-5-carboxylate is converted to glutamate by 1-pyrroline-5-carboxylate dehydrogenase.
Prosthetic group		A prosthetic group is a cofactor that is attached permanently and tightly or even covalently to an enzyme and that is regenerated in each enzymatic turnover. Thus a prostethic group is distinguished from a coenzyme or cosubstrate that is attached loosely and transiently. Like a coenzyme, the prosthetic group is required by an enzyme for its activity. A prosthetic group is 'a tightly bound, specific nonpolypeptide unit in a protein determining and involved in its biological activity' (IUPAC definition). FMN/FMNH₂ and FAD/FADH₂ are prosthetic groups of Complex I and Complex II, respectively.
Pyruvate	P	Pyruvic acid, C₃H₄O₃, is an alpha-keto monocarboxylic acid which occurs under physiological conditions mainly as the anion pyruvate^-, P, with pK_a = 2.5. Pyruvate is formed in glycolysis from phosphoenolpyruvate. In the cytosol, pyruvate is a substrate of lactate dehydrogenase. Pyruvate enters the mitochondrial matrix via a specific low K_m' H⁺/monocarboxylate cotransporter known as the pyruvate carrier. Similarly, the plasma membrane of many cell types has H⁺/monocarboxylate cotransporter activity and pyruvate can thus be added as a substrate to living cells. In the mt-matrix the oxidative decarboxylation of pyruvate is catalyzed by pyruvate dehydrogenase and yields acetyl-CoA. Pyruvate competitively reverses the inhibition of cytochrome c oxidase by cyanide. Pyruvate is an antioxidant reacting with hydrogen peroxide.
Q-pools	Q	Different Q-pools are more or less clearly distinguished in the cell, related to a variety of models describing degress of Q-pool behavior. (1) CoQ-pools are distinguished according to their compartmentation in the cell: mitochondrial CoQ (mtCoQ) and CoQ in other organelles versus plasma-membrane CoQ. (2) The total mitochondrial CoQ-pool mtCoQ is partitioned into an ETS-reactive Q-pool, Q_ra, and an inactive mtCoQ-pool, Q_ia. (2a) The Q_ra-pool is fully reduced in the form of quinol QH₂ under anoxia, and fully oxidized in the form of quinone in aerobic mitochondrial preparations incubated without CHNO-fuel substrates. Intermediate redox states of Q_ra are sensitive to pathway control and coupling control of mitochondrial electron transfer and OXPHOS. (2b) The Q_ia-pool remains partially reduced and oxidized independent of aerobic-anoxic transitions. The redox state of Q_ia is insensitive to changes in mitochondrial respiratory states. (3) The Q_ra-pool is partitioned into Q with Q-pool behavior according to the fluid-state model (synonymous: random-collision model) and Q tightly bound to supercomplexes according to the solid-state model. The two models describe the extremes in a continuum of homogenous or heterogenous Q-pool behavior. The CII-Q-CIII segment of the S-pathway is frequently considered to follow homogenous Q-pool behavior participating in the Q_hom-pool, whereas the CI-Q-CIII segment of the N-pathway indicates supercomplex organization and metabolic channeling with different degrees of Q-pool heterogeneity contributing to the Q_het-pool.
Reactive nitrogen species	RNS	Reactive nitrogen species, RNS, are nitric oxide-derived oxidants. The main source of RNS is nitric oxide (NO•). NO• plays an important role in cell signaling and in oxidative-nitrosative stress.
Reactive oxygen species	ROS	Reactive oxygen species, ROS, are molecules derived from molecular oxygen, including free oxygen radicals, which are more reactive than O₂. Physiologically and pathologically important ROS include superoxide, the hydroxyl radical and hydroxide ion, hydrogen peroxide and other peroxides. These are important in cell signalling, oxidative defence mechanisms and oxidative stress.
Substrate		IUPAC distinguishes three definitions of 'substrate': (1) The chemical entity whose conversion to a product or products is catalysed by one or several enzymes. (2) A solution or dry mixture containing all ingredients which are necessary for the growth of a microbial culture or for product formation. (3) Component in the nutrient medium, supplying the organisms with carbon (C-substrate), nitrogen (N-substrate), etc. A substrate in a chemical reaction has a negative stoichiometric number since it is consumed, whereas a product has a positive stoichiometric number since it is produced.
Substrate-uncoupler-inhibitor titration	SUIT	Mitochondrial 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.
Substrates as electron donors	S_red	Substrates as electron donors are reduced fuel compounds S_red that are oxidized to an oxidized product P_ox during H⁺-linked electron transfer, S_red → P_ox + 2{H⁺ + e^-}. Mitochondrial respiration depends on a continuous flow of electron-supplying substrates across the mitochondrial membranes into the matrix space. Many substrates are strong anions that cannot permeate lipid membranes and hence require carriers.
Succinate	S	Succinic acid, C₄H₆O₄, (butanedioic acid) is a dicarboxylic acid which occurs under physiological conditions as the anion succinate^2-, S, with pK_a1 = 4.2 and pK_a2 = 5.6. Succinate is formed in the TCA cycle, and is a substrate of CII, reacting to fumarate and feeding electrons into the Q-junction. Succinate (CII-linked) and NADH (CI-linked) provide convergent electron entries into the Q-junction. Succinate is transported across the inner mt-membrane by the dicarboxylate carrier. The plasma membrane of many cell types is impermeable for succinate (but see Zhunussova 2015 Am J Cancer Res for an exception). Incubation of mt-preparations by succinate alone may lead to accumulation of oxaloacetate, which is a potent inhibitor of Complex II (compare Succinate and rotenone). High activities of mt-Malic enzyme (mtME) prevent accumulation of oxaloacetate in incubations with succinate without rotenone.
Succinate transport		The dicarboxylate carrier catalyses the electroneutral exchange of succinate^2- for HPO_4-^2-.
Superoxide	O₂^•-	Superoxide anion, O₂^•-, is a free radical formed in a one-electron reduction of molecular oxygen (red bullet in the figure), yielding a negatively charged molecule with a single unpaired electron (blue bullet on the left). It is highly reactive with organic compounds, and its intracellular concentration is kept under control by superoxide dismutase.
TMPD	Tm	N,N,N',N'-Tetramethyl-p-phenylenediamine dihydrochloride, TMPD, is applied as an artificial substrate for reducing cytochrome c in the respirometric assay for cytochrome c oxidase (CIV) activity. It is maintained in a reduced state by ascorbate and undergoes autoxidation as a function of oxygen pressure, TMPD, ascorbate and cytochrome c concentration.
Taurine		Taurine, or 2-Aminoethan sulfonic acid, is one of the most abundant low-molecular-weight organic constituents in animals and humans. It has a multitude of functions in different types of tissue, one of which is the stabilization of membranes. Because of this and its antioxidative effect, taurine is a component of the respiration media MiR05 and MiR06 to preserve mitochondrial function.
Tetrahydrofolate	THF	Tetrahydrofolate, THF, is the substrate in mitochondrial folate-mediated 1C metabolism, an NADH-linked pathway leading to the formation of formate which is exported to the cytosol.
Volume of the solute		Most 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.
Water	H₂O	Water, H₂O, is widely used in the laboratory, particularly as a solvent and cleaning agent. Chemically pure water is prepared in various grades of purification: double distilled water (ddH₂O) versus distilled water (dH₂O or aqua destillata, a.d.) and deionized or demineralized water (diH₂O) with various combination purification methods. When H₂O is mentioned without further specification in published protocols, it is frequently assumed that the standards of each laboratory are applied as to the quality of purified water. Purification is not only to be controlled with respect to salt content and corresponding electrical conductivity (ultra-pure water: 5.5 μS/m due to H⁺ and OH^- ions), but also in terms of microbial contamination.

Semantic search

Query log