Browsing Pathways

Phospholipids are membrane components in E. coli. The major phospholipids of E. coli are phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions. The reaction starts from a glycerone phosphate (dihydroxyacetone phosphate) produced in glycolysis. The glycerone phosphate is transformed to a sn-glycerol 3-phosphate (glycerol 3 phosphate) by NADPH driven glycerol-3-phosphate dehydrogenase. Sn-glycerol 3-phosphate is transformed to a 1-acyl-sn-glycerol 3-phosphate(1-oleyl-2-lyso-phosphatidate , 1-palmitoylglycerol 3-phosphate , 1-stearoyl-sn-glycerol 3-phosphate). This can be achieve by a sn-glycerol-3-phosphate 1-0-acyltransferase that interacts either with a long-chain acyl-CoA or with an acyl-[acp]. The 1-acyl-sn-glycerol 3-phosphate is transformed into a 1,2-diacyl-sn-glycerol 3-phosphate through a 1-acylglycerol-3-phosphate O-acyltransferase. This compound is then converted into a CPD-diacylglycerol through a CTP (phosphatidate cytididyltransferase. CPD-diacylglycerol can be transformed either to a L-1-phosphatidylserine or a L-1-phosphatidylglycerol-phosphate through a phosphatidylserine synthase or a phosphatidylglycerophosphate synthase respectively. The L-1-phosphatidylserine transforms into L-1-phosphatidylethanolamine through a phosphatidylserine decarboxylase, o the other hand L-1-phosphatidylglycerol-phosphate gets transformed into a L-1-phosphatidyl-glycerol through a phosphatidylglycerophosphatase. These 2 products combines produce a cardiolipin and a ethanolamine. The L-1 phosphatidyl-glycerol can also interact with cardiolipin synthase resulting in a glycerol and a cardiolipin.

E. coli lipid A is synthesized on the cytoplasmic surface of the inner membrane. The pathway can start from the fructose 6-phosphate that is either produced in the glycolysis and pyruvate dehydrogenase or be obtained from the interaction with D-fructose interacting with a mannose PTS permease. Fructose 6-phosphate interacts with L-glutamine through a D-fructose-6-phosphate aminotransferase resulting into a L-glutamic acid and a glucosamine 6-phosphate. The latter compound is isomerized through a phosphoglucosamine mutase resulting a glucosamine 1-phosphate. This compound is acetylated, interacting with acetyl-CoA through a bifunctional protein glmU resulting in a Coenzyme A, hydrogen ion and N-acetyl-glucosamine 1-phosphate. This compound interact with UTP and hydrogen ion through the bifunctional protein glmU resulting in a pyrophosphate and a UDP-N-acetylglucosamine. This compound interacts with (3R)-3-hydroxymyristoyl-[acp] through an UDP-N-acetylglucosamine acyltransferase resulting in a holo-[acp] and a UDP-3-O[(3R)-3-hydroxymyristoyl]-N-acetyl-alpha-D-glucosamine. This compound interacts with water through UDP-3-O-acyl-N-acetylglucosamine deacetylase resulting in an acetic acid and UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine. The latter compound interacts with (3R)-3-hydroxymyristoyl-[acp] through UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase releasing a hydrogen ion, a holo-acp and UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The latter compound is hydrolase by interacting with water and a UDP-2,3-diacylglucosamine hydrolase resulting in UMP, hydrogen ion and 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate. This last compound then interacts with a UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine through a lipid A disaccharide synthase resulting in a release of UDP, hydrogen ion and a lipid A disaccharide. The lipid A disaccharide is phosphorylated by an ATP mediated tetraacyldisaccharide 4'-kinase resulting in the release of hydrogen ion and lipid IVA. A D-ribulose 5-phosphate is isomerized with D-arabinose 5-phosphate isomerase 2 to result in a D-arabinose 5-phosphate. This compounds interacts with water and phosphoenolpyruvic acid through a 3-deoxy-D-manno-octulosonate 8-phosphate synthase resulting in the release of phosphate and 3-deoxy-D-manno-octulosonate 8-phosphate. This compound interacts with water through a 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase thus releasing a phosphate and a 3-deoxy-D-manno-octulosonate. The latter compound interacts with CTP through a 3-deoxy-D-manno-octulosonate cytidylyltransferase resulting in a pyrophosphate and CMP-3-deoxy-α-D-manno-octulosonate. CMP-3-deoxy-α-D-manno-octulosonate and lipid IVA interact with each other through a KDO transferase resulting in CMP, hydrogen ion and alpha-Kdo-(2-->6)-lipid IVA. The latter compound reacts with CMP-3-deoxy-α-D-manno-octulosonate through a KDO transferase resulting in a CMP, hydrogen ion, and a a-Kdo-(2->4)-a-Kdo-(2->6)-lipid IVA. The latter compound can either react with a palmitoleoyl-acp through a palmitoleoyl acyltransferase resulting in the release of a holo-acyl carriere protein and a Kdo2-palmitoleoyl-lipid IVa which in turn reacts with a myristoyl-acp through a myristoyl-acp dependent acyltransferase resulting in a release of a holo-acp and a Kdo2-lipid A, cold adapted, or it can interact with a dodecanoyl-[acp] lauroyl acyltransferase resulting in a holo-[acp] and a (KDO)2-(lauroyl)-lipid IVA. The latter compound reacts with a myristoyl-[acp] through a myristoyl-acyl carrier protein (ACP)-dependent acyltransferase resulting in a holo-[acp], (KDO)2-lipid A. The latter compound reacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase I resulting hydrogen ion, ADP, heptosyl-KDO2-lipid A. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase II resulting in ADP, hydrogen ion and (heptosyl)2-Kdo2-lipid A. The latter compound UDP-glucose interacts with (heptosyl)2-Kdo2-lipid A resulting in UDP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A. Glucosyl-(heptosyl)2-Kdo2-lipid A (Escherichia coli) is phosphorylated through an ATP-mediated lipopolysaccharide core heptose (I) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A-phosphate. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core heptosyl transferase III resulting in ADP, hydrogen ion, and glucosyl-(heptosyl)3-Kdo2-lipid A-phosphate. The latter compound is phosphorylated through an ATP-driven lipopolysaccharide core heptose (II) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-alpha-D-galactose through a UDP-D-galactose:(glucosyl)lipopolysaccharide-1,6-D-galactosyltransferase resulting in a UDP, a hydrogen ion and a galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-glucose through a (glucosyl)LPS α-1,3-glucosyltransferase resulting in a hydrogen ion, a UDP and galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with UDP-glucose through a UDP-glucose:(glucosyl)LPS α-1,2-glucosyltransferase resulting in UDP, a hydrogen ion and galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core biosynthesis; heptosyl transferase IV; probably hexose transferase resulting in a Lipid A-core. A lipid A-core is then exported into the periplasmic space by a lipopolysaccharide ABC transporter. The lipid A-core is then flipped to the outer surface of the inner membrane by the ATP-binding cassette (ABC) transporter, MsbA. An additional integral membrane protein, YhjD, has recently been implicated in LPS export across the IM. The smallest LPS derivative that supports viability in E. coli is lipid IVA. However, it requires mutations in either MsbA or YhjD, to suppress the normally lethal consequence of an incomplete lipid A . Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface.

L-Carnitine can stimulate anaerobic growth of E.coli when exogenous electron acceptors (i.e. nitrate, etc.) are absent. During anaerobic growth, E.coli can reduce L-carnitine to γ-butyrobetaine by CoA-linked intermediates when carbon and nitrogen are present in the system. Therefore, L-carnitine may act as external electron acceptor for anaerobic growth as well as generation of an osmoprotectant for cell.

Uracil is a pyrimidine nucleobase found in RNA, and can be used as a source of nitrogen for E. coli. There are at least three pathways through which uracil is degraded. This one begins with uracil, which originates from purine degradation. The putative monooxygenase enzyme rutA catalyzes the breakdown of uracil into peroxyaminoacrylate, using FMNH2 as a cofactor. Peroxyaminoacrylate is then broken down into both carbamic acid and 3-aminoacrylate following the addition of a water molecule by the putative isochorismatase family protein rutB. Carbamic acid can then spontaneously, with the addition of a hydrogen ion, split into an ammonium ion and a molecule of carbon dioxide. 3-aminoacrylate, on the other hand, is catalyzed by the UPF0076 protein rutC to form 2-aminoacrylic acid. This compound enters into a reaction catalyzed by protein rutD, which adds a water molecule and hydrogen ion and forms malonic semialdehyde with ammonium being a byproduct. Finally, the putative NADH dehydrogenase/NAD(P)H nitroreductase rutE complex converts malonic semialdehyde into hydroxypropionic acid, which is then used to form other necessary chemicals. The ammonium ions produced will be the important source of nitrogen for the bacteria.

The selenium metabolism begins with the introduction of selenate and selenite to the cytosol through a sulphate permease system. Once in the cell, selenate can be reduced to selenite through nitrate reductases A and Z. Selenite then interacts with glutathione and 2 hydrogen ions resulting in the release of 2 water molecules, a hydroxide molecule, a glutathione disulfide and a selenodiglutathione. The latter compound then reacts with NADPH+H resulting in the release of a NADP, a glutathione and a glutathioselenol. Glutathiolselenol can then be oxidize resulting in a a glutathiolselenol ion which can then interact with a water molecule resulting in a release of glutathion and selenium Glutathiolselenol can also react with NADPH and hydrogen ion resulting in a release of glutathione, NADP, a hydroxide molecule and a hydrogen selenide. This compound can react in a reversible reaction by being oxidized resulting in a hydrogen selenide ion . This compound can then be phosphorylated by interacting with an ATP and releasing a AMP, a phosphate and a selenophosphate.

The pathway starts with trans-cinnamate interacting with a hydrogen ion, an oxygen molecule, and a NADH through a cinnamate dioxygenase resulting in a NAD and a cis-3-(3-Carboxyethenyl)-3,5-cyclohexadiene-1,2-diol which then interact together through a 2,3-dihydroxy-2,3-dihydrophenylpropionate dehydrogenase resulting in the release of a hydrogen ion, an NADH molecule and a 2,3 dihydroxy-trans-cinnamate. The second way by which the 2,3 dihydroxy-trans-cinnamate is acquired is through a 3-hydroxy-trans-cinnamate interacting with a hydrogen ion, a NADH and an oxygen molecule through a 3-(3-hydroxyphenyl)propionate 2-hydroxylase resulting in the release of a NAD molecule, a water molecule and a 2,3-dihydroxy-trans-cinnamate. The compound 2,3 dihydroxy-trans-cinnamate then interacts with an oxygen molecule through a 2,3-dihydroxyphenylpropionate 1,2-dioxygenase resulting in a hydrogen ion and a 2-hydroxy-6-oxonona-2,4,7-triene-1,9-dioate. The latter compound then interacts with a water molecule through a 2-hydroxy-6-oxononatrienedioate hydrolase resulting in a release of a hydrogen ion, a fumarate molecule and (2Z)-2-hydroxypenta-2,4-dienoate. The latter compound reacts spontaneously to isomerize into a 2-oxopent-4-enoate. This compound is then hydrated through a 2-oxopent-4-enoate hydratase resulting in a 4-hydroxy-2-oxopentanoate. This compound then interacts with a 4-hydroxy-2-ketovalerate aldolase resulting in the release of a pyruvate, and an acetaldehyde. The acetaldehyde then interacts with a coenzyme A and a NAD molecule through a acetaldehyde dehydrogenase resulting in a hydrogen ion, a NADH and an acetyl-coa which can be incorporated into the TCA cycle

The pathway can start in various spots. First step in this case starts with NADH interacting with a menaquinone oxidoreductase resulting in the release of a NADH and a hydrogen Ion, at the same time in the inner membrane a menaquinone interacts with 2 electrons and 2 hydrogen ions thus releasing a menaquinol. This allows for 4 hydrogen ions to be transferred from the cytosol to the periplasmic space. The menaquinol then interacts with a dimethyl sulfoxide reductase resulting in the release of 2 hydrogen ion and 2 electrons. At the same time dimethyl sulfoxide and 2 hydrogen ions interact with the enzyme resulting in the release of a dimethyl sulfide and a water molecule, this reaction happening in the periplasmic space. The second set of reactions starts with a hydrogen interacting with a menaquinone oxidoreductase resulting in the release of two electrons being released into the inner membrane which then react with with 2 hydrogen ion and a menaquinone to produce a menaquinol. This menaquinol then reacts with a trimethylamine N-oxide reductase following the same steps as mentioned before. The third set of reactions starts with with formate interacting with a formate dehydrogenase-O resulting in a release of carbon dioxide and a hydrogen ion, this releases 2 electrons that interact with a menaquinone and two hydrogen ions. This releases a menaquinol which then reacts with a trimethylamine N-oxide reductase following the same steps as mentioned before

Menaquinol biosynthesis starts with chorismate being metabolized into isochorismate through a isochorismate synthase. Isochorismate then interacts with 2-oxoglutare and a hydrogen ion through a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase resulting in the release of a carbon dioxide and a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate. The latter compound then interacts with (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase resulting in the release of a pyruvate and a (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate. This compound is the dehydrated through a o-succinylbenzoate synthase resulting in the release of a water molecule and a 2-succinylbenzoate. This compound then interacts with a coenzyme A and an ATP through a o-succinylbenzoate CoA ligase resulting in the release of a diphosphate, a AMP and a succinylbenzoyl-CoA. The latter compound interacts with a hydrogen ion through a 1,4-dihydroxy-2-naphthoyl-CoA synthase resulting in the release of a water molecule or a 1,4-dihydroxy-2-naphthoyl-CoA. This compound then interacts with water through a 1,4-dihydroxy-2-naphthoyl-CoA thioesterase resulting in the release of a coenzyme A, a hydrogen ion and a 1,4-dihydroxy-2-naphthoate. The 1,4-dihydroxy-2-naphthoate can interact with either farnesylfarnesylgeranyl-PP or octaprenyl diphosphate and a hydrogen ion through a 1,4-dihydroxy-2-naphthoate octaprenyltransferase resulting in a release of a carbon dioxide, a pyrophosphate and a demethylmenaquinol-8. This compound then interacts with SAM through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a hydrogen ion, a s-adenosyl-L-homocysteine and a menaquinol.

The process of oleic acid B-oxidation starts with a 2-trans,5-cis-tetradecadienoyl-CoA that can be either be processed by an enoyl-CoA hydratase by interacting with a water molecules resulting in a 3-hydroxy-5-cis-tetradecenoyl-CoA, which can be oxidized in the fatty acid beta-oxidation. On the other hand 2-trans,5-cis-tetradecadienoyl-CoA can become a 3-trans,5-cis-tetradecadienoyl-CoA through a isomerase. This results interact with a water molecule through a acyl-CoA thioesterase resulting in a hydrogen ion, a coenzyme A and a 3,5-tetradecadienoate

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.