2.0 2012-07-30 14:55:03 -0600 2015-09-13 12:56:15 -0600 ECMDB21232 M2MDB001640 Hydrogen peroxide Hydrogen peroxide (H2O2) is the simplest peroxide (a compound with an oxygen-oxygen single bond). It is also a strong oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. The oxidizing capacity of hydrogen peroxide is so strong that it is considered a highly reactive oxygen species. Organisms also naturally produce hydrogen peroxide as a by-product of oxidative metabolism. Consequently, nearly all living things (specifically, all obligate and facultative aerobes) possess enzymes known as catalase peroxidases, which harmlessly and catalytically decompose low concentrations of hydrogen peroxide to water and oxygen. (Wikipedia) Hydrogen peroxide (H2O2) is a very pale blue liquid which appears colourless in a dilute solution, slightly more viscous than water. It is a weak acid. It has strong oxidizing properties and has also found use as a disinfectant and as an oxidizer. Hydrogen peroxide (H2O2) is a well-documented component of living cells. It plays important roles in host defense and oxidative biosynthetic reactions. In addition, there is growing evidence that at low levels, H2O2 also functions as a signaling agent, particularly in higher organisms. (HMDB) In E. coli, H2O2 is used in the aerobic degradation of L-ascorbate, and produced as a byproduct in many reactions involving oxygen as an oxidizing agent. (EcoCyc) In E. coli glyoxylate metabolism, H2O2 is produced as a byproduct of the conversion of glycolate to glyoxylate by the enzyme glycolate oxidase (EC 1.1.3.15), and H2O2 is then converted to harmless O2 by the enzyme catalase (EC 1.11.1.6). (KEGG) Adeka Super EL Albone Albone 35 Albone DS Anti-Keim 50 Asepticper Baquashock Bis(hydridooxygen)(OO) CIX Clarigel Gold Crestal Whitestrips Crystacide Dentasept Deslime LP Dihydrogen dioxide Dihydrogen peroxide Dihydrogen(peroxide) Dioxidane Elawox H2O2 H<SUB>2</SUB>O<SUB>2</SUB> Hioxyl Hipox HOOH Hybrite Hydrogen dioxide Hydrogen dioxide solution Hydrogen oxide Hydrogen peroxide Hydrogen peroxide (H2O2) Hydrogen peroxide solution (DOT) Hydrogen peroxide, 90% Hydrogen peroxide, solution Hydroperoxide Inhibine Lase Peroxide Lensan A Lensept Magic Bleaching Metrokur Mirasept Nite White Excel 2 Odosat D Opalescence Xtra Oxigenal Oxydol Oxyfull Oxysept Oxysept I Pegasyl Perhydrol Perone Peroxaan Peroxclean Peroxide Quasar Brite Select Bleach Superoxol T-Stuff Whiteness HP Whitespeed Xtra White [OH(OH)] H2O2 34.0147 34.005479308 peroxol hydrogen peroxide 7722-84-1 OO InChI=1S/H2O2/c1-2/h1-2H MHAJPDPJQMAIIY-UHFFFAOYSA-N Liquid Cytosol Extra-organism Periplasm melting_point -0.43 oC logp -0.45 ChemAxon pka_strongest_acidic 11.52 ChemAxon pka_strongest_basic -4.2 ChemAxon iupac peroxol ChemAxon average_mass 34.0147 ChemAxon mono_mass 34.005479308 ChemAxon smiles OO ChemAxon formula H2O2 ChemAxon inchi InChI=1S/H2O2/c1-2/h1-2H ChemAxon inchikey MHAJPDPJQMAIIY-UHFFFAOYSA-N ChemAxon polar_surface_area 40.46 ChemAxon refractivity 5.13 ChemAxon polarizability 2.29 ChemAxon rotatable_bond_count 0 ChemAxon acceptor_count 2 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Glutathione metabolism The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. PW000833 ec00480 Metabolic Alanine, aspartate and glutamate metabolism ec00250 Tyrosine metabolism ec00350 Phenylalanine metabolism The pathways of the metabolism of phenylalaline begins with the conversion of chorismate to prephenate through a P-protein (chorismate mutase:pheA). Prephenate then interacts with a hydrogen ion through the same previous enzyme resulting in a release of carbon dioxide, water and a phenolpyruvic acid. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine. Phenolpyruvic acid can also be obtained from a reversivle reaction with ammonia, a reduced acceptor and a D-amino acid dehydrogenase, resulting in a water, an acceptor and a D-phenylalanine, which can be then transported into the periplasmic space by aromatic amino acid exporter. L-phenylalanine also interacts in two reversible reactions, one involved with oxygen through a catalase peroxidase resulting in a carbon dioxide and 2-phenylacetamide. The other reaction involved an interaction with oxygen through a phenylalanine aminotransferase resulting in a oxoglutaric acid and phenylpyruvic acid. L-phenylalanine can be imported into the cytoplasm through an aromatic amino acid:H+ symporter AroP. The compound can also be imported into the periplasmic space through a transporter: L-amino acid efflux transporter. PW000921 ec00360 Metabolic Isoquinoline alkaloid biosynthesis ec00950 Tropane, piperidine and pyridine alkaloid biosynthesis ec00960 Glycine, serine and threonine metabolism ec00260 Methane metabolism ec00680 Vitamin B6 metabolism ec00750 Tryptophan metabolism The biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan. The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA PW000815 ec00380 Metabolic Porphyrin and chlorophyll metabolism ec00860 Glyoxylate and dicarboxylate metabolism ec00630 Nicotinate and nicotinamide metabolism ec00760 beta-Alanine metabolism The Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate. Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets. PW000896 ec00410 Metabolic Phenylpropanoid biosynthesis ec00940 Arachidonic acid metabolism Delete Pathway Arachidonate (arachidonic acid) is a polyunsaturated ω-6 fatty acid with a 20-carbon chain and four cis-double bonds. It is produced at high levels by mosses, some plants, and by some marine bacteria. Mammals cannot synthesize arachidonate de novo, but most mammals are able to synthesize it from simpler unsaturated fatty acids. In addition to being involved in cellular signaling as a lipid second messenger, arachidonate is also a key inflammatory intermediate and can also act as a vasodilator. Like other fatty acids, arachidonate is rarely found in its free form. It is usually found either as arachidonoyl-CoA or incorporated into a lipid. It is produced from phosphatidylcholine through a phospholipase A1 PW000759 ec00590 Metabolic Microbial metabolism in diverse environments ec01120 Metabolic pathways eco01100 Ascorbate metabolism E. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions. Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate. This compound is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate.This compound is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate. L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate. The compound 3-keto-L-gulonate 6-phosphate can be processed aerobically or anaerobically. Aerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate. This compound in turn is changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. This compound again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate. This compound can then be part of the pentose phosphate pathway. Anaerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate. This compound in turn is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. This compound again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. This compound can then be part of the pentose phosphate pathway. Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP. Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen. PW000793 Metabolic Aspartate metabolism Aspartate (seen in the center) is synthesized from and degraded to oxaloacetate , an intermediate of the TCA cycle, by a reversible transamination reaction with glutamate. As shown here, AspC is the principal transaminase that catalyzes this reaction, but TyrB also catalyzes it. Null mutations in aspC do not confer aspartate auxotrophy; null mutations in both aspC and tyrB do. Aspartate is a constituent of proteins and participates in several other biosyntheses as shown here( NAD biosynthesis and Beta-Alanine Metabolism . Approximately 27 percent of the cell's nitrogen flows through aspartate Aspartate can be synthesized from fumaric acid through a aspartate ammonia lyase. Aspartate also participates in the synthesis of L-asparagine through two different methods, either through aspartate ammonia ligase or asparagine synthetase B. Aspartate is also a precursor of fumaric acid. Again it has two possible ways of synthesizing it. First set of reactions follows an adenylo succinate synthetase that yields adenylsuccinic acid and then adenylosuccinate lyase in turns leads to fumaric acid. The second way is through argininosuccinate synthase that yields argininosuccinic acid and then argininosuccinate lyase in turns leads to fumaric acid PW000787 Metabolic NAD biosynthesis Nicotinamide adenine dinucleotide (NAD) can be biosynthesized from L-aspartic acid.This amino acid reacts with oxygen through an L-aspartate oxidase resulting in a hydrogen ion, hydrogen peroxide and an iminoaspartic acid. The latter compound interacts with dihydroxyacetone phosphate through a quinolinate synthase A, resulting in a phosphate, water, and a quinolic acid. Quinolic acid interacts with phosphoribosyl pyrophosphate and hydrogen ion through a quinolinate phosphoribosyltransferase resulting in pyrophosphate, carbon dioxide and nicotinate beta-D-ribonucleotide. This last compound is adenylated through an ATP driven nicotinate-mononucleotide adenylyltransferase releasing a pyrophosphate and resulting in a nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide is processed through an NAD synthetase, NH3-dependent in two different manners. In the first case, Nicotinic acid adenine dinucleotide interacts with ATP, L-glutamine and water through the enzyme and results in hydrogen ion, AMP, pyrophosphate, L-glutamic acid and NAD. In the second case, Nicotinic acid adenine dinucleotide interacts with ATP and ammonium through the enzyme resulting in a pyrophosphate, AMP, hydrogen ion and NAD. NAD then proceeds to regulate its own pathway by repressing L-aspartate oxidase. As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate , while in eukaryotes, the de novo pathway starts with tryptophan. PW000829 Metabolic Porphyrin metabolism The metabolism of porphyrin begins with with glutamic acid being processed by an ATP-driven glutamyl-tRNA synthetase by interacting with hydrogen ion and tRNA(Glu), resulting in amo, pyrophosphate and L-glutamyl-tRNA(Glu) Glutamic acid. Glutamic acid can be obtained as a result of L-glutamate metabolism pathway, glutamate / aspartate : H+ symporter GltP, glutamate:sodium symporter or a glutamate / aspartate ABC transporter . L-glutamyl-tRNA(Glu) Glutamic acid interacts with a NADPH glutamyl-tRNA reductase resulting in a NADP, a tRNA(Glu) and a (S)-4-amino-5-oxopentanoate. This compound interacts with a glutamate-1-semialdehyde aminotransferase resulting a 5-aminolevulinic acid. This compound interacts with a porphobilinogen synthase resulting in a hydrogen ion, water and porphobilinogen. The latter compound interacts with water resulting in hydroxymethylbilane synthase resulting in ammonium, and hydroxymethylbilane. Hydroxymethylbilane can either be dehydrated to produce uroporphyrinogen I or interact with a uroporphyrinogen III synthase resulting in a water molecule and a uroporphyrinogen III. Uroporphyrinogen I interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a coproporphyrinogen I Uroporphyrinogen III can be metabolized into precorrin by interacting with a S-adenosylmethionine through a siroheme synthase resulting in hydrogen ion, an s-adenosylhomocysteine and a precorrin-1. On the other hand, Uroporphyrinogen III interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a Coproporphyrinogen III. Precorrin-1 reacts with a S-adenosylmethionine through a siroheme synthase resulting in a S-adenosylhomocysteine and a Precorrin-2. The latter compound is processed by a NAD dependent uroporphyrin III C-methyltransferase [multifunctional] resulting in a NADH and a sirohydrochlorin. This compound then interacts with Fe 2+ uroporphyrin III C-methyltransferase [multifunctional] resulting in a hydrogen ion and a siroheme. The siroheme is then processed in sulfur metabolism pathway. Uroporphyrinogen III can be processed in anaerobic or aerobic condition. Anaerobic: Uroporphyrinogen III interacts with an oxygen molecule, a hydrogen ion through a coproporphyrinogen III oxidase resulting in water, carbon dioxide and protoporphyrinogen IX. The latter compound then interacts with an 3 oxygen molecule through a protoporphyrinogen oxidase resulting in 3 hydrogen peroxide and a Protoporphyrin IX Aerobic: Uroporphyrinogen III reacts with S-adenosylmethionine through a coproporphyrinogen III dehydrogenase resulting in carbon dioxide, 5-deoxyadenosine, L-methionine and protoporphyrinogen IX. The latter compound interacts with a meanquinone through a protoporphyrinogen oxidase resulting in protoporphyrin IX. The protoporphyrin IX interacts with Fe 2+ through a ferrochelatase resulting in a hydrogen ion and a ferroheme b. The ferroheme b can either be incorporated into the oxidative phosphorylation as a cofactor of the enzymes involved in that pathway or it can interact with hydrogen peroxide through a catalase HPII resulting in a heme D. Heme D can then be incorporated into the oxidative phosphyrlation pathway as a cofactor of the enzymes involved in that pathway. Ferroheme b can also interact with water and a farnesyl pyrophosphate through a heme O synthase resulting in a release of pyrophosphate and heme O. Heme O is then incorporated into the Oxidative phosphorylation pathway. PW000936 Metabolic Vitamin B6 1430936196 PW000891 Metabolic arginine metabolism The metabolism of L-arginine starts with the acetylation of L-glutamic acid resulting in a N-acetylglutamic acid while releasing a coenzyme A and a hydrogen ion. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NDPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde. This compound reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine which is then deacetylated through a acetylornithine deacetylase which yield an ornithine. L-glutamine is used to synthesize carbamoyl phosphate through the interaction of L-glutamine, water, ATP, and hydrogen carbonate. This reaction yields ADP, L-glutamic acid, phosphate, and hydrogen ion. Carbamoyl phosphate and ornithine are used to catalyze the production of citrulline through an ornithine carbamoyltransferase. Citrulline reacts with L-aspartic acid through an ATP dependent enzyme, argininosuccinate synthase to produce pyrophosphate, AMP and argininosuccinic acid. Argininosussinic acid is then lyase to produce L-arginine and fumaric acid. L-arginine can be metabolized into succinic acid by two different sets of reactions: 1. Arginine reacts with succinyl-CoA through a arginine N-succinyltransferase resulting in N2-succinyl-L-arginine while releasing CoA and Hydrogen Ion. N2-succinyl-L-arginine is then dihydrolase to produce a N2-succinyl-L-ornithine through a N-succinylarginine dihydrolase. This compound in turn reacts with oxoglutaric acid through succinylornithine transaminase resulting in L-glutamic acid and N2-succinyl-L-glutamic acid 5-semialdehyde. This compoud in turn reacts with a NAD dependent dehydrogenase resulting in N2-succinylglutamate while releasing NADH and hydrogen ion. N2-succinylglutamate reacts with water through a succinylglutamate desuccinylase resulting in L-glutamic acid and a succinic acid. The succinic acid is then incorporated in the TCA cycle 2.Argine reacts with carbon dioxide and a hydrogen ion through a biodegradative arginine decarboxylase, resulting in Agmatine. This compound is then transformed into putrescine by reacting with water and an agmatinase, and releasing urea. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. This compound is dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. This compound reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid. Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. This compound in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle. L-arginine is eventua lly metabolized into succinic acid which then goes to the TCA cycle PW000790 Metabolic ornithine metabolism In the ornithine biosynthesis pathway of E. coli, L-glutamate is acetylated to N-acetylglutamate by the enzyme N-acetylglutamate synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NADPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde. This compound reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine which is then deacetylated through a acetylornithine deacetylase which yield an ornithine. Ornithine interacts with hydrogen ion through a Ornithine decarboxylase resulting in a carbon dioxide release and a putrescine Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. This compound is dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. This compound reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid. Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. This compound in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle. PW000791 Metabolic Phenylethylamine metabolism The process of phenylethylamine metabolism starts with 2-phenylethylamine interacting with an oxygen molecule and a water molecule in the periplasmic space through a phenylethylamine oxidase. This reaction results in the release of a hydrogen peroxide, ammonium and phenylacetaldehyde. Phenylacetaldehyde is introduced into the cytosol and degraded into phenylacetate by reaction with a phenylacetaldehyde dehydrogenase. This reaction involves phenylacetaldehyde interacting with NAD, and a water molecule and then resulting in the release of NADH, and 2 hydrogen ion. Phenylacetate is then degraded. The first step involves phenylacetate interacting with an coenzyme A and an ATP driven phenylacetate-CoA ligase resulting in the release of a AMP, a diphosphate and a phenylacetyl-CoA. This resulting compound the interacts with a hydrogen ion, NADPH, and oxygen molecule through a ring 1,2-phenylacetyl-CoA epoxidase protein complex resulting in the release of a water molecule, an NADP and a 2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA. This compound is then metabolized by a ring 1,2 epoxyphenylacetyl-CoA isomerase resulting in a 2-oxepin-2(3H)-ylideneacetyl-CoA. This compound is then hydrolated through a oxepin-CoA hydrolase resulting in a 3-oxo-5,6-didehydrosuberyl-CoA semialdehyde. This commpound then interacts with a water molecule and NADP driven 3-oxo-5,6-dehydrosuberyl-CoA semialadehyde dehydrogenase resulting in 2 hydrogen ions, a NADPH and a 3-oxo-5,6-didehydrosuberyl-CoA. The resulting compound interacts with a coenzyme A and a 3-oxo-5,6 dehydrosuberyl-CoA thiolase resulting in an acetyl-CoA and a 2,3-didehydroadipyl-CoA. This resulting compound is the hydrated by a 2,3-dehydroadipyl-CoA hydratas resulting in a 3-hydroxyadipyl-CoA whuch is dehydrogenated through an NAD driven 3-hydroxyadipyl-CoA dehydrogenase resulting in a NADH, a hydrogen ion and a 3-oxoadipyl-CoA. The latter compound then interacts with conezyme A through a beta-ketoadipyl-CoA thiolase resulting in an acetyl-CoA and a succinyl-CoA. The succinyl-CoA is then integrated into the TCA cycle. PW002027 Metabolic Putrescine Degradation II Several metabolic pathways for putrescine degradation as a source of nitrogen for E. coli K-12 are known. The first putrescine degradation pathway was found in in 1985. That pathway is dedicated to the degradation of intracellular putrescine. A second pathway was found in E. coli K-12 twenty years later. This pathway seems to be dedicated to the degradation of extracellular putrescine. The pathway was discovered following the discovery of a cluster of seven unassigned genes on the E. coli K-12 chromosome. In addition to a putrescine transporter, encoded by the puuP gene, the cluster contains four genes that encode the enzymes involved in this pathway, and two additional genes (puuE and puuR) that encode an enzyme involved in the catabolism of GABA (see superpathway of 4-aminobutanoate degradation) and a regulator. In this pathway, putrescine is γ-glutamylated at the expense of an ATP molecule. The resulting γ-glutamyl-putrescine is oxidized to γ-glutamyl-γ-aminobutyraldehyde, which is then dehydrogenated into 4-(glutamylamino) butanoate. In the last step, the γ-glutamyl group is removed by hydrolysis, generating 4-aminobutyrate. The key difference between this pathway and putrescine degradation I is the γ-glutamylation of putrescine. In the other pathway, putrescine is degraded directly to 4-amino-butanal. Wild type E. coli cells are unable to utilize putrescine as the sole source of carbon at temperatures above 30°C. It is possible to select for mutants that possess this ability; these mutants contain elevated levels of the enzymes in this pathway. (EcoCyc) PW002054 Metabolic Superoxide Radicals Degradation Gram-negative bacteria commonly synthesize both cytoplasmic and periplasmic isozymes of SOD as their frontline defense against superoxide anion (O2-). E. coli contains two cytoplasmic SOD isozymes, one each of the manganese- and iron-cofactored types (MnSOD and FeSOD), and secretes a copper, zinc-cofactored enzyme (CuZnSOD) to the periplasm. Periplasmic superoxide may be generated by autooxidation of dihydromenaquinone in the cytoplasmic membrane. In E. coli, the MnSOD and FeSOD enzymes (encoded by sodA and sodB, respectively) are structurally and kinetically similar. Unlike MnSOD and FeSOD, CuZnSOD is monomeric. Regulation of the three enzymes is complex. Under anaerobic conditions, FeSOD is the only superoxide dismutase enzyme present in E. coli. MnSOD is induced by aerobic growth and a variety of environmental stress conditions. CuZnSOD constitutes only a small fraction of superoxide dismutase activity in the cell; its expression is induced in stationary phase. In E. coli, with rising H2O2 concentration, catalase is strongly induced and becomes the primary scavenging enzyme. E. coli expresses two catalases, known as HPI and HPII, that are encoded by katG and katE, respectively. While katG katE mutants could not degrade millimolar concentrations of H2O2, they were subsequently found to retain the ability to degrade H2O2 when it was present at low micromolar concentrations. This residual activity is due to an enzyme known as alkylhydroperoxide reductase (Ahp). This two-component enzyme had originally been identified as a scavenger of organic hydroperoxides. SOD mutants of E. coli are unable to perform normal sulfur metabolism. Both SOD and catalase/peroxidase mutants of E. coli are incapable of synthesizing aromatic products, including amino acids. SoxRS regulon is turned on by any condition that increases superoxide radical production in E. coli. One of its products is Mn-SOD. Another independent regulon turned on in response to H2O2 is referred to as the OxyR regulon. (EcoCyc) PW002053 Metabolic L-threonine degradation to methylglyoxal L-threonine is degrade into methylglyoxal (pyruvaldehyde) by first reacting with a NDA dependent threonine dehydrogenase resulting in the release of a hydrogen ion, an NADH and a 2-amino-3-oxobutanoate. The latter compound reacts spontaneously with a hydrogen ion resulting in the release of a carbon dioxide and a aminoacetone. The aminoacetone in turn reacts with an oxygen and a water molecule through an aminoacetone oxidase resulting in the release of a hydrogen peroxide, ammonium and a methylglyoxal which can then be incorporated in the methylglyoxal degradation pathways. PW002106 Metabolic L-ascorbate degradation II (bacterial, aerobic) PWY-6961 NAD biosynthesis I (from aspartate) PYRIDNUCSYN-PWY threonine degradation III (to methylglyoxal) THRDLCTCAT-PWY phenylethylamine degradation I 2PHENDEG-PWY pyridoxal 5'-phosphate salvage pathway PLPSAL-PWY pyridoxal 5'-phosphate biosynthesis I PYRIDOXSYN-PWY putrescine degradation II PWY0-1221 heme biosynthesis from uroporphyrinogen-III I HEME-BIOSYNTHESIS-II superpathway of heme biosynthesis from uroporphyrinogen-III PWY0-1415 superoxide radicals degradation DETOX1-PWY Specdb::CMs 3384 Specdb::CMs 132497 Specdb::CMs 140231 Specdb::MsMs 28757 Specdb::MsMs 28758 Specdb::MsMs 28759 Specdb::MsMs 35315 Specdb::MsMs 35316 Specdb::MsMs 35317 Specdb::MsMs 2413402 Specdb::MsMs 2413403 Specdb::MsMs 2413404 Specdb::MsMs 2552306 Specdb::MsMs 2552307 Specdb::MsMs 2552308 HMDB03125 784 763 C00027 16240 HYDROGEN-PEROXIDE PER Hydrogen_peroxide Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Gonzalez-Flecha, B., Demple, B. (1997). "Homeostatic regulation of intracellular hydrogen peroxide concentration in aerobically growing Escherichia coli." J Bacteriol 179:382-388. 8990289 Lopez-Lazaro M: Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy. Cancer Lett. 2007 Jul 8;252(1):1-8. Epub 2006 Dec 5. 17150302 Schallreuter KU, Elwary S: Hydrogen peroxide regulates the cholinergic signal in a concentration dependent manner. Life Sci. 2007 May 30;80(24-25):2221-6. Epub 2007 Jan 25. 17335854 Stone JR, Yang S: Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):243-70. 16677071 Tredwin CJ, Naik S, Lewis NJ, Scully C: Hydrogen peroxide tooth-whitening (bleaching) products: review of adverse effects and safety issues. Br Dent J. 2006 Apr 8;200(7):371-6. 16607324 Ardanaz N, Pagano PJ: Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Exp Biol Med (Maywood). 2006 Mar;231(3):237-51. 16514169 http://hmdb.ca/system/metabolites/msds/000/002/708/original/HMDB03125.pdf?1358461854 Superoxide dismutase [Mn] P00448 SODM_ECOLI sodA http://ecmdb.ca/proteins/P00448.xml Vitamin B12 transport periplasmic protein BtuE P06610 BTUE_ECOLI btuE http://ecmdb.ca/proteins/P06610.xml Protoporphyrinogen oxidase P0ACB4 HEMG_ECOLI hemG http://ecmdb.ca/proteins/P0ACB4.xml Putative peroxiredoxin bcp P0AE52 BCP_ECOLI bcp http://ecmdb.ca/proteins/P0AE52.xml Glycolate oxidase subunit glcD P0AEP9 GLCD_ECOLI glcD http://ecmdb.ca/proteins/P0AEP9.xml Superoxide dismutase [Cu-Zn] P0AGD1 SODC_ECOLI sodC http://ecmdb.ca/proteins/P0AGD1.xml Superoxide dismutase [Fe] P0AGD3 SODF_ECOLI sodB http://ecmdb.ca/proteins/P0AGD3.xml Thioredoxin-2 P0AGG4 THIO2_ECOLI trxC http://ecmdb.ca/proteins/P0AGG4.xml L-aspartate oxidase P10902 NADB_ECOLI nadB http://ecmdb.ca/proteins/P10902.xml Catalase-peroxidase P13029 KATG_ECOLI katG http://ecmdb.ca/proteins/P13029.xml Catalase HPII P21179 CATE_ECOLI katE http://ecmdb.ca/proteins/P21179.xml Adenine deaminase P31441 ADEC_ECOLI ade http://ecmdb.ca/proteins/P31441.xml Malate:quinone oxidoreductase P33940 MQO_ECOLI mqo http://ecmdb.ca/proteins/P33940.xml Probable cytochrome c peroxidase P37197 YHJA_ECOLI yhjA http://ecmdb.ca/proteins/P37197.xml Gamma-glutamylputrescine oxidoreductase P37906 PUUB_ECOLI puuB http://ecmdb.ca/proteins/P37906.xml Primary amine oxidase P46883 AMO_ECOLI tynA http://ecmdb.ca/proteins/P46883.xml Glycolate oxidase iron-sulfur subunit P52074 GLCF_ECOLI glcF http://ecmdb.ca/proteins/P52074.xml Glycolate oxidase subunit glcE P52073 GLCE_ECOLI glcE http://ecmdb.ca/proteins/P52073.xml N-methyl-L-tryptophan oxidase P40874 MTOX_ECOLI solA http://ecmdb.ca/proteins/P40874.xml Thioredoxin-1 P0AA25 THIO_ECOLI trxA http://ecmdb.ca/proteins/P0AA25.xml Pyridoxine/pyridoxamine 5'-phosphate oxidase P0AFI7 PDXH_ECOLI pdxH http://ecmdb.ca/proteins/P0AFI7.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml Hydrogen peroxide + Reduced Thioredoxin >2 Water + Oxidized Thioredoxin 2 Hydrogen peroxide <>2 Water + Oxygen R00009 CATAL-RXN 2 Hydrogen ion + 2 Superoxide anion > Hydrogen peroxide + Oxygen SUPEROX-DISMUT-RXN Water + Oxygen + Sarcosine > Formaldehyde + Glycine + Hydrogen peroxide N-Methyltryptophan + Water + Oxygen > Formaldehyde + Hydrogen peroxide + L-Tryptophan RXN0-301 gamma-Glutamyl-L-putrescine + Water + Oxygen > gamma-Glutamyl-gamma-butyraldehyde + Hydrogen peroxide + Ammonium RXN0-3921 Dopamine + Water + Oxygen > 3,4-Dihydroxyphenylacetaldehyde + Hydrogen peroxide + Ammonium Water + Oxygen + Tyramine > 4-Hydroxyphenylacetaldehyde + Hydrogen peroxide + Ammonium Water + Oxygen + Phenylethylamine > Hydrogen peroxide + Ammonium + Phenylacetaldehyde Water + Oxygen + Pyridoxamine 5'-phosphate > Hydrogen peroxide + Ammonium + Pyridoxal 5'-phosphate Oxygen + Pyridoxine 5'-phosphate > Hydrogen peroxide + Pyridoxal 5'-phosphate R00278 PNPOXI-RXN 2 Glutathione + Hydrogen peroxide <> Glutathione disulfide +2 Water R00274 GLUTATHIONE-PEROXIDASE-RXN L-Aspartic acid + Oxygen <> Hydrogen ion + Hydrogen peroxide + Iminoaspartic acid R00481 L-ASPARTATE-OXID-RXN Hydrogen peroxide + L-Methionine > Water + Methionine sulfoxide 2 [4Fe-4S] iron-sulfur cluster + 2 Hydrogen ion + Hydrogen peroxide >2 [3Fe-4S] damaged iron-sulfur cluster +2 Fe3+ +2 Water Pyridoxamine 5'-phosphate + Water + Oxygen <> Pyridoxal 5'-phosphate + Ammonia + Hydrogen peroxide R00277 PMPOXI-RXN Pyridoxine 5'-phosphate + Oxygen <> Hydrogen peroxide + Pyridoxal 5'-phosphate R00278 L-Aspartic acid + Water + Oxygen <> Oxalacetic acid + Ammonia + Hydrogen peroxide R00357 Glycolic acid + Oxygen <> Glyoxylic acid + Hydrogen peroxide R00475 L-Aspartic acid + Oxygen <> Iminoaspartic acid + Hydrogen peroxide R00481 L-ASPARTATE-OXID-RXN Methanol + Hydrogen peroxide <> Formaldehyde +2 Water R00602 Pyridoxamine + Water + Oxygen <> Pyridoxal + Ammonia + Hydrogen peroxide R01710 Pyridoxine + Oxygen <> Pyridoxal + Hydrogen peroxide R01711 Tyramine + Water + Oxygen <> 4-Hydroxyphenylacetaldehyde + Ammonia + Hydrogen peroxide R02382 Aminoacetone + Water + Oxygen <> Pyruvaldehyde + Ammonia + Hydrogen peroxide R02529 Phenylethylamine + Oxygen + Water <> Phenylacetaldehyde + Ammonia + Hydrogen peroxide R02613 2 3-Hydroxyanthranilic acid + 4 Oxygen <> Cinnavalininate +2 Superoxide anion +2 Hydrogen peroxide +2 Hydrogen ion R02670 1,3-Diaminopropane + Oxygen + Water <> 3-Aminopropionaldehyde + Ammonia + Hydrogen peroxide R03139 N-Methylputrescine + Oxygen + Hydrogen ion <> 1-Methylpyrrolinium + Hydrogen peroxide + Ammonia R04027 Dopamine + Water + Oxygen <> 3,4-Dihydroxyphenylacetaldehyde + Ammonia + Hydrogen peroxide R04300 Methylamine + Oxygen + Water <> Formaldehyde + Ammonia + Hydrogen peroxide R06154 Cadaverine + Water + Oxygen <> 5-Aminopentanal + Ammonia + Hydrogen peroxide R06740 gamma-Glutamyl-L-putrescine + Water + Oxygen <> gamma-Glutamyl-gamma-butyraldehyde + Ammonia + Hydrogen peroxide R07415 Hydrogen ion + Hydrogen peroxide + Iron > hydroxyl radical + OH<SUP>-</SUP> + Fe<SUP>3+</SUP> RXN-12540 dehydroascorbate (bicyclic form) + Hydrogen peroxide > L-threonate + Oxalic acid + Hydrogen ion RXN-12863 Ascorbic acid + Hydrogen peroxide > monodehydroascorbate + Water RXN-3521 Heme + Hydrogen peroxide Heme D RXN-8073 NAD(P)H + Cr⁶⁺ + Oxygen > NAD(P)⁺ + Cr³⁺ + Hydrogen peroxide RXN0-3381 L-Methionine + Hydrogen peroxide > L-methionine <i>S</i>-oxide + Water RXN0-6721 Aminoacetone + Water + Oxygen > Hydrogen ion + Pyruvaldehyde + Ammonia + Hydrogen peroxide R02529 AMACETOXID-RXN an aliphatic amine + Water + Oxygen > an aldehyde + Ammonia + Hydrogen peroxide + Hydrogen ion AMINEOXID-RXN Water + Oxygen + Phenylethylamine > Hydrogen ion + Hydrogen peroxide + Ammonia + Phenylacetaldehyde R02613 AMINEPHEN-RXN Hydrogen peroxide > Water + Oxygen CATAL-RXN Hydrogen peroxide + Glutathione > Glutathione disulfide + Water GLUTATHIONE-PEROXIDASE-RXN Oxygen + L-Aspartic acid > Hydrogen ion + Hydrogen peroxide + Iminoaspartic acid L-ASPARTATE-OXID-RXN L-Malic acid + Oxygen <> Oxalacetic acid + Hydrogen peroxide MALOX-RXN a phenolic donor + Hydrogen peroxide a phenoxyl radical of a phenolic donor + Water PEROXID-RXN Oxygen + Water + Pyridoxamine 5'-phosphate > Hydrogen ion + Hydrogen peroxide + Ammonia + Pyridoxal 5'-phosphate PMPOXI-RXN Protoporphyrinogen IX + Oxygen > Protoporphyrin IX + Hydrogen peroxide PROTOPORGENOXI-RXN a reduced electron acceptor + Hydrogen peroxide > an oxidized electron acceptor + Water RXN-12120 Hydrogen peroxide > Water + Oxygen RXN-12121 Ascorbic acid + Hydrogen peroxide + Hydrogen ion > Ascorbic acid + L-dehydro-ascorbate + Water RXN-12440 a primary amine + Water + Oxygen > an aldehyde + Ammonia + Hydrogen peroxide RXN-9597 L-2-Hydroxyglutaric acid + Oxygen > Oxoglutaric acid + Hydrogen peroxide RXN0-5364 Hydrogen ion + Superoxide anion > Hydrogen peroxide + Oxygen SUPEROX-DISMUT-RXN RCH(2)NH(2) + Water + Oxygen > RCHO + Ammonia + Hydrogen peroxide Phenylethylamine + Water + Oxygen > Phenylacetaldehyde + Ammonia + Hydrogen peroxide 2 Hydrogen peroxide > Oxygen +2 Water 2 Iron + Hydrogen peroxide + 2 Hydrogen ion >2 Fe3+ +2 Water Donor + Hydrogen peroxide > oxidized donor +2 Water (S)-2-hydroxy acid + Oxygen > 2-oxo acid + Hydrogen peroxide N-methyl-L-tryptophan + Water + Oxygen > L-Tryptophan + Formaldehyde + Hydrogen peroxide L-Aspartic acid + Oxygen > Iminoaspartic acid + Hydrogen peroxide Pyridoxamine 5'-phosphate + Water + Oxygen > Pyridoxal 5'-phosphate + Ammonia + Hydrogen peroxide gamma-Glutamyl-L-putrescine + Water + Oxygen > Gamma-glutamyl-gamma-aminobutyraldehyde + Ammonia + Hydrogen peroxide 2 superoxide + 2 Hydrogen ion > Oxygen + Hydrogen peroxide 2 Ferrocytochrome c + Hydrogen peroxide >2 Ferricytochrome c +2 Water 2 Hydrogen ion + 2 superoxide <> Oxygen + Hydrogen peroxide R00275 Reduced acceptor + Hydrogen peroxide <> Acceptor + Water + Oxygen R03532 Primary amine + Water + Oxygen <> Aldehyde + Ammonia + Hydrogen peroxide R01853 Pyridoxamine 5'-phosphate + Water + Oxygen + Pyridoxine 5'-phosphate <> Pyridoxal 5'-phosphate + Ammonia + Hydrogen peroxide R00277 (S)-2-Hydroxyacid + Oxygen <> 2-Oxo acid + Hydrogen peroxide R01341 Ferrocytochrome c + Hydrogen peroxide <> Ferricytochrome c + Water R00017 Protoporphyrinogen IX + 3 Oxygen <> Protoporphyrin IX +3 Hydrogen peroxide R03222 L-Aspartic acid + Water + Oxygen + L-Aspartic acid > Oxalacetic acid + Ammonia + Hydrogen peroxide PW_R002645 L-Aspartic acid + Oxygen + L-Aspartic acid > Hydrogen peroxide + Hydrogen ion + Iminoaspartic acid PW_R003007 gamma-Glutamyl-L-putrescine + Oxygen + Water > 4-(γ-glutamylamino)butanal + Ammonium + Hydrogen peroxide PW_R002686 Protoporphyrinogen IX + 3 Oxygen > Protoporphyrin IX +3 Hydrogen peroxide PW_R003484 ferroheme b + Hydrogen peroxide > Heme D PW_R003488 gamma-Glutamyl-L-putrescine + Oxygen + Hydrogen ion > gamma-Glutamyl-gamma-butyraldehyde + Hydrogen peroxide + Ammonium PW_R005998 Aminoacetone + Oxygen + Water > Hydrogen peroxide + Ammonium + Pyruvaldehyde PW_R006139 L-Aspartic acid + Oxygen <> Hydrogen ion + Hydrogen peroxide + Iminoaspartic acid Oxygen + Pyridoxine 5'-phosphate > Hydrogen peroxide + Pyridoxal 5'-phosphate 2 Hydrogen peroxide <>2 Water + Oxygen gamma-Glutamyl-L-putrescine + Water + Oxygen <> gamma-Glutamyl-gamma-butyraldehyde + Ammonia + Hydrogen peroxide 2 Hydrogen ion + 2 superoxide <> Oxygen + Hydrogen peroxide Glycolic acid + Oxygen <> Glyoxylic acid + Hydrogen peroxide L-Aspartic acid + Oxygen <> Hydrogen ion + Hydrogen peroxide + Iminoaspartic acid Oxygen + Pyridoxine 5'-phosphate > Hydrogen peroxide + Pyridoxal 5'-phosphate 2 Hydrogen ion + 2 superoxide <> Oxygen + Hydrogen peroxide Glycolic acid + Oxygen <> Glyoxylic acid + Hydrogen peroxide Glycolic acid + Oxygen <> Glyoxylic acid + Hydrogen peroxide Luria-Bertani Broth Shake flask 0.25 uM 0.03 37 oC AB1157/K12 Mid-Log Phase 1000 120 Gonzalez-Flecha, B., Demple, B. (1997). "Homeostatic regulation of intracellular hydrogen peroxide concentration in aerobically growing Escherichia coli." J Bacteriol 179:382-388. 8990289 Luria-Bertani Broth Shake flask 0.18 uM 0.02 37 oC AB1157/K12 Stationary Phase 720 80 Gonzalez-Flecha, B., Demple, B. (1997). "Homeostatic regulation of intracellular hydrogen peroxide concentration in aerobically growing Escherichia coli." J Bacteriol 179:382-388. 8990289