MitoPedia: Enzymes

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MitoPedia: Enzymes

MitoPedia - high-resolution terminology - matching measurements at high-resolution.
The MitoPedia terminology is developed continuously in the spirit of Gentle Science.

AMPKAMPKAMP-activated protein kinase is a regulatory protein which acts as crucial cellular energy sensor by sensing AMP, ADP and/or Ca2+ levels in response to metabolic stresses or drug administration.
ATP synthaseCVATP synthase or F-ATPase (the use of Complex V is discouraged) catalyzes the endergonic phosphorylation of ADP to ATP in an over-all exergonic process that is driven by proton translocation along the protonmotive force.
Acyl-CoA oxidaseAcyl-CoA oxidase is considered as a rate-limiting step in peroxysomal β-oxidation, which carries out few β-oxidation cycles, thus shortening very-long-chain fatty acids (>C20). Electrons are directly transferred from FADH2 to O2 with the formation of H2O2.
Adenine nucleotide translocaseANTThe adenine nucleotide translocator, ANT, exchanges ADP for ATP in an electrogenic antiport across the inner mt-membrane. The ANT is inhibited by atractyloside, carboxyatractyloside and bongkrekik acid. The ANT is a component of the phosphorylation system.
Adenylate kinaseADKAdenylate kinase, which is also called myokinase, is a phosphotransferase enzyme that is located in the mitochondrial intermembrane space and catalyzes the rephosphorylation of AMP to ADP in the reaction ATP + AMP ↔ ADP + ADP.
Alternative oxidaseAOXThe alternative oxidase is a membrane-bound enzyme capable of supporting cyanide-and antimycin A-resistant mitochondrial respiration. It catalyzes the oxidation of ubiquinol and the reduction of oxygen to water in a four electron process. As this bypasses several proton-translocating steps, inducton of this alternative pathway is associated with a dramatic reduction of ATP production. Expression and activity of the enzyme is modified by environmental conditions such as temperature, oxidative stress, nutrient availability, as well as by pathogens such as viruses. AOX can be found in most plants, many fungi and protists, but is not expressed in animals.
Biochemical threshold effectDue to threshold effects, even a large defect diminishing the velocity of an individual enzyme results in only minor changes of pathway flux.
Carnitine O-octanoyltransferaseCOTCarnitine O-octanoyltransferase is a mitochondrial enzyme that transfers carnitine to octanoyl-CoA to form Coenzyme A and octanoylcarnitine: Octanoyl-CoA + L-carnitine ↔ CoA + L-octanoylcarnitine.
Carnitine acetyltransferaseCrATCarnitine acetyltransferase (CrAT) is located in the mitochondrial matrix and catalyses the formation of acetyl-carnitine from acetyl-CoA and L-carnitine and thus regulates the acetyl-CoA/free CoA ratio which is essential for pyruvate dehydrogenase complex (PDC) activity.
Carnitine acyltransferaseCarnitine acyltransferases mediate the transport of long-chain fatty acids across the inner mt-membrane by binding them to carnitine. First, long-chain fatty acids are activated by an energy-requiring step in which the fatty acid ester of CoA is formed enzymatically at the expense of ATP. The fatty acids then pass through the inner mt-membrane and enter the mitochondria as carnitine esters. The fatty acyl group is then transferred from carnitine to intramitochondrial CoA and the resulting fatty acyl CoA is used as a substrate in the fatty acid oxidation (FAO) cycle in the mt-matrix.
Carnitine palmitoyltransferase ICPT 1Carnitine palmitoyltransferase I (CPT 1) is a regulatory enzyme in mitochondrial long-chain acyl-CoA uptake and further oxidation. CPT 1 is associated with the outer mt-membrane and catalyses the formation of acylcarnitines from acyl-CoA and L-carnitine. There are three enzyme isoforms: CPT 1A (liver type), CPT 1B (muscle type), CPT 1C (brain type). Isoforms have significantly different kinetic and regulatory properties. Malonyl-CoA is an endogenous inhibitor of CPT 1.
Carnitine-acylcarnitine translocaseCACTCarnitine-acylcarnitine translocase (CACT) transports acyl-carnitines into the mitochondrial matrix in exchange for free L-carnitine.
CatalaseCtlCatalase catalyzes the dismutation of hydrogen peroxide to water and oxygen. Perhaps all cells have catalase, but mitochondria of most cells lack catalase. Cardiac mitochondria are exceptional in having mt-catalase activity (rat heart mitochondria: Radi et al 1991; mouse heart mitochondria: Rindler et al 2013).
Catalytic activitykatCatalytic activity of an enzyme is measured by an enzyme assay and is expressed in units of katal (kat [mol∙s-1]). More commonly (but not conforming to SI units or IUPAC recommendations) enzyme activity is expressed in units U [mol∙min-1].
Choline dehydrogenaseCholine dehydrogenase (EC is bound to the inner mt-membrane, oxidizes choline in kidney and liver mitochondria, with electron transfer into the Q-junction, and is thus part of the ET-pathway. Analogous to succinate dehydrogenase (CII), electron transfer from choline dehydrogenase is FAD-linked downstream to Q. Choline is an ET-pathway substrate types 3.
Citrate synthaseCSCondensation of oxaloacetate with acetyl-CoA yields citrate as an entry into the TCA cycle, with CS located in the mt-matrix.
Coenzyme ACoACoenzyme A is a coenzyme playing an essential role in the tricarboxylic acid cycle (oxidation of pyruvate to acetyl-CoA) and fatty acid oxidation. CoA is a thiol that reacts with carboxylic acids to form CoA-activated thioesters.
Coenzyme QQ, CoQCoenzyme Q, redox system (oxidized ubiquinone, partially reduced semiquinone, fully reduced ubiquinol) of the ET-pathway. More details » Q-junction.
Complex ICIComplex I, NADH:ubiquinone oxidoreductase (EC, is an enzyme complex of the Electron transfer-pathway, a proton pump across the inner mt-membrane, responsible for electron transfer to ubiquinone from NADH formed in the mt-matrix. CI forms a supercomplex with Complex III.
Complex IICIIComplex II or succinate:quinone oxidoreductase (SQR) is the only membrane-bound enzyme in the TCA cycle and is part of the ET-pathway. The flavoprotein succinate dehydrogenase is the largest polypeptide of CII, located on the matrix face of the mt-inner membrane. Following succinate oxidation, the enzyme transfers electrons directly to the quinone pool.
Complex IIICIIIComplex III or coenzyme Q : cytochrome c - oxidoreductase, sometimes also called the cytochrome bc1 complex is a complex of the ET-pathway. It catalyzes the reduction of cytochrome c by oxidation of coenzyme Q (CoQ) and the concomitant pumping of 4 protons from the mitochondrial matrix to the intermembrane space.
Complex IVCIVComplex IV or cytochrome c oxidase is the terminal oxidase of the mitochondrial ET-pathway, reducing oxygen to water, with reduced cytochrome c as a substrate. CIV is frequently abbreviated as COX or CcO. It is the 'ferment' (Atmungsferment) of Otto Warburg, shown to be related to the cytochromes discovered by David Keilin.
Creatine kinaseCKThe mitochondrial creatine kinase, also known as phosphocreatine kinase (CPK), facilitates energy transport with creatine and phosphocreatine as diffusible intermediates.
Dicarboxylate carrierDICThe dicarboxylate carrier is a transporter which catalyses the electroneutral exchange of malate2- (or succinate2-) for inorganic phosphate, HPO42-.
Dihydro-orotate dehydrogenaseDhoDHDihydro-orotate dehydrogenase is an electron transfer complex of the inner mitochondrial membrane, converting dihydro-orotate (Dho) into orotate, and linking electron transfer through the Q-junction to pyrimidine synthesis and thus to the control of biogenesis.
Electron transfer-pathwayET-pathwayIn the mitochondrial electron transfer-pathway (ET-pathway) electrons are transfered from externally supplied reduced fuel substrates to oxygen. Based on this experimentally oriented definition (see ET-capacity), the ET-pathway consists of (1) the membrane-bound ET-pathway with respiratory complexes located in the inner mt-membrane, (2) TCA cycle and other mt-matrix dehydrogenases generating NADH and succinate, and (3) the carriers involved in metabolite transport across the mt-membranes. » MiPNet article
Electron-transferring flavoprotein complexCETFElectron-transferring flavoprotein complex (CETF) or electron-transferring flavoprotion is a respiratory complex localized at the matrix face of the inner mitochondrial membrane, supplies electrons from fatty acid oxidation (FAO, ß-oxidation) to CoQ, and is thus an enzyme complex of the mitochondrial Electron transfer-pathway (ET-pathway).
FumaraseFHFumarase or fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle catalyzing the equilibrium reaction between fumarate and malate. Fumarase is found not only in mitochondria, but also in the cytoplasm of all eukaryotes.
Glutamate dehydrogenasemtGDHGlutamate dehydrogenase, located in the mitochondrial matrix (mtGDH), is an enzyme that converts glutamate to α-ketoglutarate [1]. mtGDH is not part of the TCA cycle, but is involved in glutaminolysis as an anaplerotic reaction.
Glycerophosphate dehydrogenase complexCGpDHGlycerophosphate dehydrogenase complex (CGpDH) is a complex of the Electron transfer-pathway localized at the outer face of the inner mt-membrane. CGpDH is thus distinguished from cytosolic GpDH. CGpDH oxidizes glycerophosphate to dihydroxyacetone phosphate and feeds two electrons ino the Q-junction, thus linked to an ET pathway level 3 control state.
Glycerophosphate shuttleGp shuttle
The glycerophosphate shuttle makes cytoplasmic NADH available for mitochondrial oxidative phosphorylation. Cytoplasmic NADH reacts with dihydroxyacetone phosphate catalyzed by cytoplasmic glycerophosphate dehydrogenase. On the outer face of the inner mitochondrial membrane, glycerophosphate dehydrogenase complex (mitochondrial glycerophosphate dehydrogenase) oxidizes glycerophosphate back to dihydroxyacetone phosphate, a reaction not generating NADH but reducing a flavin prosthesic group. The reduced flavoprotein transfers its reducing equivalents into the Q-junction, thus representing a ET pathway level 3 control state.
HexokinaseHKThe hexokinase catalyzes the phosphorylation of D-glucose at position 6 by ATP to yield D-glucose 6-phosphate as well as the phosphorylation of many other hexoses like D-fructose, D-mannose, D-glucosamine.
Isocitrate dehydrogenaseIDHIsocitrate dehydrogenase forms 2-oxoglutarate from isocitrate in the TCA cycle.
Kynurenine hydroxylaseKynurenine hydroxylase (kynurenine 3-monooxygenase) is located in the outer mitochondrial membrane. Kynurenine hydroxylase catalyzes the chemical reaction: L-kynurenine + NADPH + H+ + O2 ↔ 3-hydroxy-L-kynurenine + NADP+ + H2O Kynurenine hydroxylase belongs to the family of oxidoreductases acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor. This enzyme participates in tryptophan metabolism. It employs one cofactor, FAD.
Lactate dehydrogenaseLDHLactate dehydrogenase is a glycolytic marker enzyme in the cytosol, regenerating NAD+ from NADH and pyruvate, forming lactate.
Malate dehydrogenasemtMDHMitochondrial malate dehydrogenase is localized in the mitochondrial matrix and oxidizes malate, generated from fumarate by fumarase, to oxaloacetate, reducing NAD+ to NADH+H+ in the TCA cycle. Malate is added as a substrate in most N-pathway control states.
Malate-aspartate shuttleThe malate-aspartate shuttle involves the glutamate-aspartate carrier and the 2-oxoglutarate carrier exchanging malate2- for 2-oxoglutarate2-. Cytosolic and mitochondrial malate dehydrogenase and transaminase complete the shuttle for the transport of cytosolic NADH into the mitochondrial matrix. It is most important in heart, liver and kidney.
Malic enzymemtMEMalic enzyme (ME; EC catalyzes the oxidative decarboxylation of L-malate to pyruvate with the concomitant reduction of the dinucleotide cofactor NAD+ or NADP+ and a requirement for divalent cations (Mg2+ or Mn2+) as cofactors.

NAD(P)+ + L-malate2- <--> NAD(P)H + pyruvate- + CO2

Three groups of ME are distinguished (i) NAD+- and (ii) NADP+-dependent ME specific for NAD+ or NADP+, respectively, and (iii) NAD(P)+- dependent ME with dual specificity for NAD+ or NADP+ as cofactor. Three isoforms of ME have been identified in mammals: cytosolic NADP+-dependent ME (cNADP-ME or ME1), mitochondrial NAD(P)+-dependent ME (mtNAD-ME or ME2; with NAD+ or NADP+ as cofactor, preference for NAD+ under physiological conditions), and mitochondrial NADP+-dependent ME (mtNADP-ME or ME3). mtNAD-ME plays an important role in anaplerosis when glucose is limiting, particularly in heart and skeletal muscle. Tartronic acid (hydroxymalonic acid) is an inhibitor of ME.
Malonyl-CoA synthaseMalonyl-CoA synthase or ACSF3 protein is a mitochondrial fatty-acyl-CoA synthase found in mammals. Traditionally, malonyl-CoA is formed from acetyl-CoA by the action of acetyl-CoA carboxylase. However, Witkowski et al (2011) showed that mammals express malonyl-CoA Synthase (ACSF3) with enzymatic activity in the presence of malonate (Complex II inhibitor) and methylmalonate.
Membrane-bound ET-pathwaymET-pathwayThe membrane-bound electron transfer-pathway (mET-pathway) consists in mitochondria mainly of respiratory complexes CI, CII, electron transferring flavoprotein complex (CETF), glycerophosphate dehydrogenase complex (CGpDH), and choline dehydrogenase, with convergent electron flow at the Q-junction (Coenzyme Q), and the two downstream respiratory complexes connected by cytochrome c, CIII and CIV, with oxygen as the final electron acceptor. The mET-pathway is the terminal (downstream) module of the mitochondrial ET-pathway and can be isoled from the ET-pathway in submitochondrial particles (SmtP).
Mitochondrial ATP-sensitive K+ channelmtKATPThe mitochondrial ATP-sensitive K+ channel (mtKATP or mitoKATP).
Mitochondrial markermt-markerMitochondrial markers are structural or functional properties that are specific for mitochondria. A structural mt-marker is the area of the inner mt-membrane or mt-volume determined stereologically, which has its limitations due to different states of swelling. If mt-area is determined by electron microscopy, the statistical challenge has to be met to convert area into a volume. When fluorescent dyes are used as mt-marker, distinction is necessary between mt-membrane potential dependent and independent dyes. mtDNA or cardiolipin content may be considered as a mt-marker. Mitochondrial marker enzymes may be determined as molecular (amount of protein) or functional properties (enzyme activities). Respiratory capacity in a defined respiratory state of a mt-preparation can be considered as a functional mt-marker, in which case respiration in other respiratory states is expressed as flux control ratios. » MiPNet article
Mitochondrial marker enzymesMitochondrial marker enzymes are enzymes that are specifically present in mitochondria, in the mt-matrix, the inner mt-membrane, the inter-membrane space, or the outer mt-membrane.
Monoamine oxidaseMAOMonoamine oxidases are enzymes bound to the outer membrane of mitochondria and they catalyze the oxidative deamination of monoamines. Oxygen is used to remove an amine group from a molecule, resulting in the corresponding aldehyde and ammonia. Monoamine oxidases contain the covalently bound cofactor FAD and are, thus, classified as flavoproteins.
NagarseNagarse is a broad specifity protease from bacteria used to promote breakdown of the cellular structure of "hard" tissues such as skeletal muscle or heart mucsle that cannot be homogenized easily without treatment with a protease. Nagarse is frequently used in protocols for isolating mitochondria from muscle tissue.
Nitric oxide synthaseNOSNitric oxide synthase, NOS, catalyzes the production of nitric oxide (NO•), which is a reactive nitrogen species. There are four types of NOS: neuronal NOS (nNOS), endothelial NOS (eNOS), inducible NOS (iNOS) and mitochondrial NOS (mtNOS).
Oxoglutarate dehydrogenaseOgDHOxoglutarate dehydrogenase (α-ketoglutarate dehydrogenase) is a highly regulated enzyme of the tricarboxylic acid cycle. It catalyses the conversion of oxoglutarate (alpha-ketoglutarate) to succinyl-CoA, reduces NAD+ to NADH and thus links to Complex I in the Electron transfer-pathway. OgDH is activated by low Ca2+ (<20 µM) but inactivated by high Ca2+ (>100 µM). OgDH is an important source of ROS.
Phosphate carrierPiCThe phosphate carrier (PiC) is a proton/phosphate symporter which transports negatively charged inorganic phosphate across the inner mt-membrane. The transport can be described either as symport of H+ with Pi, or antiport of hydroxide anion against Pi. The phosphate carrier is a component of the phosphorylation system.
Phosphoenolpyruvate carboxykinasePEPCKPhosphoenolpyruvate carboxykinase (PEPCK) catalyzes the anabolic reaction of oxaloacetate (Oxa) to phosphoenolpyruvate at the expense of GTP. PEPCK is a cytoplasmatic enzyme involved in gluconeogenesis in mouse and rat liver, but 'is found in the mitochondria in the rabbit and chicken, and in both cytoplasm and mitochondria in the guinea pig' (Lehninger 1970). In many anoxia-resistant animals, PEPCK plays an important catabolic role under severe hypoxia and anoxia at the PEPCK branchpoint (Hochachka, Somero 2002), feeding malate into the reversed TCA cycle: malate is dismutated to pyruvate catalyzed by malic enzyme in the oxidative direction, and to fumarate in the reductive direction, leading to formation of succinate and ATP under anoxia (Gnaiger 1977).
Phosphorylation systemDT
From Gnaiger 2014 MitoPathways
The phosphorylation system is the functional unit utilizing the protonmotive force to phosphorylate ADP (D) to ATP (T), and may be defined more specifically as the phosphorylation system or P»-system. The P»-system consists of adenine nucleotide translocase, phosphate carrier, and ATP synthase. Mitochondrial adenylate kinase, mt-creatine kinase and mt-hexokinase constitute extended components of the P»-system, controlling local AMP and ADP concentrations and forming metabolic channels. Since substrate-level phosphorylation is involved in the TCA-cycle, the P»-system includes succinyl-CoA ligase (GDP to GTP or ADP to ATP).
Proton pumpMitochondrial proton pumps are large enzyme complexes (CI, CII, CIV, CV) spanning the inner mt-membrane, partially encoded by mtDNA. CI, CII and CIV are proton pumps that drive protons against the electrochemical protonmotive force, driven by electron transfer from reduced substrates to oxygen. In contrast, CV is a proton pump that utilizes the energy of proton flow along the protonmotive force to drive phosphorylation of ADP to ATP.
Pyruvate carboxylasePCPyruvate carboxylase synthesizes oxaloacetate from pyruvate and CO2 as an anaplerotic reaction in the mitochondrial matrix of the liver and kidney of higher animals, representing an alternative to the malic enzyme pathway to oxaloacetate (which is more important in heart an skeletal muscle) or the phosphoenolpyruvate carboxykinase reaction (compare glyoxylate cycle in plants and microorganisms). Carboxylation of pyruvate to oxaloacetate requires Mg-ATP. Acetyl CoA is a strong positive modulator. PC can form pyruvate from oxaloacetate to remove an excess of oxaloacetate which inhibits succinate dehydrogenase.
Pyruvate carrierThe monocarboxylic acid pyruvate- is exchanged electroneutrally for OH- by the pyruvate carrier. H+/anion symport is equivalent to OH-/anion antiport.
Pyruvate dehydrogenasePDHPyruvate dehydrogenase is the first component enzyme of the pyruvate dehydrogenase complex, which catalyzes oxidative decarboxylation of pyruvate in the mt-matrix, and yields acetyl-CoA. PDH is known as the mitochondrial gatekeeper in the core energy pathway of electron flow into the tricarboxylic acid cycle.
Pyruvate dehydrogenase complexPDHCOxidative decarboxylation of pyruvate is catalyzed by the pyruvate dehydrogenase complex in the mt-matrix, and yields acetyl-CoA.
P»-systemP»systemThe ADP-ATP phosphorylation system or P»-system. See Phosphorylation system.
The Q-junction is a junction for convergent electron flow in the Electron transfer-pathway (ET-pathway) from type N substrates and mt-matix dehydrogenases through Complex I (CI), from type F substrates and FA oxidation through electron-transferring flavoprotein complex (CETF), from succinate (S) through Complex II (CII), from glycoreophosphate (Gp) through glycerophosphate dehydrogenase complex (CGpDH), from choline through choline dehydrogenase, from dihydro-orotate through dihydro-orotate dehydrogenase, and other enzyme complexes into the Q-cycle (ubiquinol/ubiquinone), and further downstream to Complex III (CIII) and Complex IV (CIV). The concept of the Q-junction, with the N-junction and F-junction upstream, provides the rationale for defining Electron transfer-pathway states and categories of SUIT protocols.
Respiratory complexesCiRespiratory complexes are membrane-bound enzymes consisting of several subunits which are involved in energy transduction of the respiratory system. » MiPNet article
Reverse electron flow from CII to CIReverse electron flow from CII to CI stimulates production of ROS when mitochondria are incubated with succinate without rotenone.
SirtuinsSirtSirtuins are NAD+-dependent deacetylases which play a prominent role as metabolic regulators. Their dependence on intracellular levels of NAD+ (NAD+ activates sirtuin activity, whereas NADH inhibits it) makes them suitable as sensors that can detect cellular energy status. » MiPNet article
Succinate dehydrogenaseSDHSuccinate dehydrogenase is a TCA cycle enzyme converting succinate to fumarate, largest component of the mt-inner membrane Complex II (CII) and thus part of the ET-pathway.
Succinyl-CoA ligaseSUCLA, SUCLGSuccinyl-CoA ligase (SUCLA or SUCLG) is a TCA cycle enzyme converting succinyl-CoA + ADP or (GDP) + Pi to succinate + ATP (GTP). Two different isoforms exsist: SUCLA (EC: is the ATP-forming isoenzyme, SUCLG (EC: is the GTP-forming isoenzyme. Both reactions are reversible. This reaction is attributed to mitochondrial substrate-level phosphorylation, which is considered as an alternative way of ATP synthesis because it is partially independent from the respiratory chain and from the mitochondrial proton motive force.
Sulfide quinone reductaseSQRSulfide quinone reductase (SQR) is involved in electron transfer from sulfide which is used as a hydrogen donor by the mitochondrial respiratory system. SQR is associated with a dioxygenase and a sulfur transferase to release thiosulfate (H2S2O3).
Sulfite oxidaseSOSulfite oxidase (SO) is a dimeric enzyme, located in the intermembrane space of mitochondria, with each monomer containing a single Mo cofactor and cyt b5-type heme [1]. SO catalyzes the oxidation of sulfite to sulfate as the terminal step in the metabolism of sulfur amino acids and is vital for human health. Inherited mutations in SO result in severe neurological problems, stunted brain growth, and early death [2].

Function: SO catalyzes the terminal reaction in the oxidative degradation of sulfur amino acids with the formation of a sulfate, electrons pass to cytochrom c and are further utilized in the respiratory system.

Sulfite + O2 + H2O --> Sulfate + H2O2

Localization: The level of expression of SO differs in various tissues with main predominant localization in liver, kidney, skeletal muscle, heart, placenta, and brain in humans and liver, kidney, heart, brain, and lung in rats [3].

Deficiency: SO is vital for metabolic pathways of sulfur amino acids (cysteine and methionine). Complete lack of this enzyme, typically caused by gene mutation, leads to lethal disease called sulfite oxidase deficiency characterized by neurological abnormalities with brain atrophy.
Superoxide dismutaseSODMammalian superoxide dismutase (SOD) exists in three forms, of which the Mn-SOD occurs in mitochondria (mtSOD, SOD2; 93 kD homotetramer) and many bacteria, in contrast to the Cu-Zn forms of SOD (cytosolic SOD1, extracellular SOD3 anchored to the extracellular matrix and cell surface). Superoxide anion (O2•-) is a major reactive oxygen species (ROS) which is dismutated by SOD to oxygen and H2O2.
Tricarboxylate carrierThe tricarboxylate carrier in the inner mt-membrane exchanges malate2- for citrate3- or isocitrate3-, with co-transport of H+.