Browsing Pathways

The synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction catalyzed by N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate. N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound can either be isomerized or deaminated into Beta-D-fructofuranose 6-phosphate through a glucosamine-fructose-6-phosphate aminotransferase and a glucosamine-6-phosphate deaminase respectively. Glucosamine 6-phosphate undergoes a reversible reaction to glucosamine 1 phosphate through a phosphoglucosamine mutase. This compound is then acetylated through a bifunctional protein glmU to produce a N-Acetyl glucosamine 1-phosphate. N-Acetyl glucosamine 1-phosphate enters the nucleotide sugar synthesis by reacting with UTP and hydrogen ion through a bifunctional protein glmU releasing pyrophosphate and a Uridine diphosphate-N-acetylglucosamine.This compound can either be isomerized into a UDP-N-acetyl-D-mannosamine or undergo a reaction with phosphoenolpyruvic acid through UDP-N-acetylglucosamine 1-carboxyvinyltransferase releasing a phosphate and a UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate. UDP-N-acetyl-D-mannosamine undergoes a NAD dependent dehydrogenation through a UDP-N-acetyl-D-mannosamine dehydrogenase, releasing NADH, a hydrogen ion and a UDP-N-Acetyl-alpha-D-mannosaminuronate, This compound is then used in the production of enterobacterial common antigens. UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate is reduced through a NADPH dependent UDP-N-acetylenolpyruvoylglucosamine reductase, releasing a NADP and a UDP-N-acetyl-alpha-D-muramate. This compound is involved in the D-glutamine and D-glutamate metabolism.

Beta-D-glucuronosides, D-glucuronate and D-fructuronate can be used as a source of carbon for E.coli. They are imported into E.coli's periplasmic space by membrane-associated protein (UidC/gusC), and are further imported into cytoplasm by hydrogen symporter. Beta-glucuronides undergoes hydrolysis by beta-D-glucuronidase to form D-glucuronate. D-glucuronate is isomerized by D-glucuronate isomerase to form D-fructuronate. D-fructuronate is further reduced to D-mannonate by D-mannonate oxidoreductase. D-mannonate dehydratase dehydrated to yield 2-dehydro-3-deoxy-D-gluconate. At this point, a common enzyme, 2-keto-3-deoxygluconokinase, phosphorylates 2-dehydro-3-deoxy-D-gluconate to yield 2-dehydro-3-deoxy-D-gluconate-6-phosphate. This product is then process by KHG/KDPG aldolase which in turn produces D-Glyceraldehyde 3-phosphate and Pyruvic Acid which then go into their respective sub pathways: glycolysis and pyruvate dehydrogenase. The pathway can also start from 3 other points: a hydrogen ion symporter (gluconate/fructuronate transporter GntP) of D-fructuronate, a hydrogen ion symporter (Hexuronate transporter) of aldehydo-D-galacturonate that spontaneously turns into D-tagaturonate. This compound can also be obtained by the reaction of aldehydo-L-galactonate with a NAD dependent l-galactonate oxidoreductase resulting in the release of NADH, hydrogen ion. Tagaturonate then undergoes an NADH-dependent reduction to D-altronate through an altronate oxidoreductase. D-altronate undergoes dehydration to yield 2-dehydro-3-deoxy-D-gluconate, the third and last point where the reaction can start from a hydrogen symporter of a 2-dehydro-3-deoy-D-gluconate.

The fatty acid biosynthesis starts from acetyl-CoA reacting either with a holo-[acp] through a 3-oxoacyl-[acp] synthase 3 resulting in an acetyl-[acp] or react with hydrogen carbonate through an ATP driven acetyl-CoA carboxylase resulting in a malonyl-CoA. Malonyl-CoA reacts with a holo-acp] through a malonyl-CoA-ACP transacylase resulting in a malonyl-[acp]. This compound can react with a KASI protein resulting in an acetyl-[acp]. A malonyl-[acp] can also react with an acetyl-[acp] through KASI and KASII or with acetyl-CoA through a beta-ketoacyl-ACP synthase to produce an acetoacetyl-[acp]. An acetoacetyl-[acp] is also known as a 3-oxoacyl-[acp]. A 3-oxoacyl-[acp] is reduced through a NDPH mediated 3-oxoacyl-[acp] reductase resulting in a (3R)-3-hydroxyacyl-[acp] (R3 hydroxydecanoyl-[acp]) which can either join the fatty acid metabolism, be dehydrated by an 3R-hydroxymyristoyl-[acp] dehydratase to produce a trans-2-enoyl-[acp] or be dehydrated by a hydroxydecanoyl-[acp] to produce a trans-delta2 decenoyl-[acp]. Trans-2-enoyl-[acp] is reduced by a NADH driven enoyl-[acp] reductase resulting in a 2,3,4-saturated fatty acyl-[acp]. This product then reacts with malonyl-[acp] through KASI and KASII resulting in a holo-acyl carrier protein and a 3- oxoacyl-[acp]. Trans-delta2 decenoyl-[acp] reacts with a 3-hydroxydecanoyl-[acp] dehydrase producing a cis-delta 3-decenoyl-ACP. This product then reacts with KASI to produce a 3-oxo-cis-delta5-dodecenoyl-[acp], which in turn is reduced by a NADPH driven 3-oxoacyl-[acp] resulting in a 3R-hydroxy cis delta5-dodecenoyl-acp. This product is dehydrated by a (3R)-hydroxymyristoyl-[acp] dehydratase resulting in a trans-delta 3- cis-delta 5-dodecenoyl-[acp] which in turn is reduced by a NADH driven enoyl-[acp] reductase resulting in a cis-delta5-dodecenoyl-acp which becomes a metabolite of fatty acid metabolism

The fatty acid biosynthesis starts from acetyl-CoA reacting either with a holo-[acp] through a 3-oxoacyl-[acp] synthase 3 resulting in an acetyl-[acp] or react with hydrogen carbonate through an ATP driven acetyl-CoA carboxylase resulting in a malonyl-CoA. Malonyl-CoA reacts with a holo-acp] through a malonyl-CoA-ACP transacylase resulting in a malonyl-[acp]. This compound can react with a KASI protein resulting in an acetyl-[acp]. A malonyl-[acp] can also react with an acetyl-[acp] through KASI and KASII or with acetyl-CoA through a beta-ketoacyl-ACP synthase to produce an acetoacetyl-[acp]. An acetoacetyl-[acp] is also known as a 3-oxoacyl-[acp]. A 3-oxoacyl-[acp] is reduced through a NDPH mediated 3-oxoacyl-[acp] reductase resulting in a (3R)-3-hydroxyacyl-[acp] (R3 hydroxydecanoyl-[acp]) which can either join the fatty acid metabolism, be dehydrated by an 3R-hydroxymyristoyl-[acp] dehydratase to produce a trans-2-enoyl-[acp] or be dehydrated by a hydroxydecanoyl-[acp] to produce a trans-delta2 decenoyl-[acp]. Trans-2-enoyl-[acp] is reduced by a NADH driven enoyl-[acp] reductase resulting in a 2,3,4-saturated fatty acyl-[acp]. This product then reacts with malonyl-[acp] through KASI and KASII resulting in a holo-acyl carrier protein and a 3- oxoacyl-[acp]. Trans-delta2 decenoyl-[acp] reacts with a 3-hydroxydecanoyl-[acp] dehydrase producing a cis-delta 3-decenoyl-ACP. This product then reacts with KASI to produce a 3-oxo-cis-delta5-dodecenoyl-[acp], which in turn is reduced by a NADPH driven 3-oxoacyl-[acp] resulting in a 3R-hydroxy cis delta5-dodecenoyl-acp. This product is dehydrated by a (3R)-hydroxymyristoyl-[acp] dehydratase resulting in a trans-delta 3- cis-delta 5-dodecenoyl-[acp] which in turn is reduced by a NADH driven enoyl-[acp] reductase resulting in a cis-delta5-dodecenoyl-acp which becomes a metabolite of fatty acid metabolism

The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway

S-adenosyl-L-methionine biosynthesis(SAM) is synthesized in the cytosol of the cell from L-methionine and ATP. This reaction is catalyzed by methionine adenosyltransferase. L methione is taken up from the environment through a complex reaction coupled transport and then proceeds too synthesize the s adenosylmethionine through a adenosylmethionine synthase. S-adenosylmethionine then interacts with a hydrogen ion through an adenosylmethionine decarboxylase resulting in a carbon dioxide and a S-adenosyl 3-methioninamine. This compound interacts with a putrescine through a spermidine synthase resulting in a spermidine, a hydrogen ion and a S-methyl-5'-thioadenosine. The latter compound is degraded by interacting with a water molecule through a 5' methylthioadenosine nucleosidase resulting in an adenine and a S-methylthioribose which is then release into the environment

The degradation of galactose, also known as Leloir pathway, requires 3 main enzymes once Beta-D-galactose has been converted to galactose through an Aldose-1-epimerase. These are: galactokinase , galactose-1-phosphate uridylyltransferase and UDP-glucose 4-epimerase. Beta-D-galactose can be uptaken from the environment through a galactose proton symporter. It can also be produced by lactose degradation involving a lactose permease to uptake lactose from the environment and a beta-galactosidase to turn lactose into Beta-D-galactose. Galactose is degraded through the following process: Beta-D-galactose is introduced into the cytoplasm through a galactose proton symporter, or it can be synthesized from an alpha lactose that is introduced into the cytoplasm through a lactose permease. Alpha lactose interacts with water through a beta-galactosidase resulting in a beta-D-glucose and beta-D-galactose. Beta-D-galactose is isomerized into D-galactose. D-Galactose undergoes phosphorylation through a galactokinase, hence producing galactose 1 phosphate. On the other side of the pathway, a gluose-1-phosphate (product of the interaction of alpha-D-glucose 6-phosphate with a phosphoglucomutase resulting in a alpha-D-glucose-1-phosphate, an isomer of Glucose 1-phosphate, or an isomer of Beta-D-glucose 1-phosphate) interacts with UTP and a hydrogen ion in order to produce a uridine diphosphate glucose. This is followed by the interaction of galactose-1-phosphate with an established amount of uridine diphosphate glucose through a galactose-1-phosphate uridylyltransferase, which in turn output a glucose-1-phosphate and a uridine diphosphate galactose. The glucose -1-phosphate is transformed into a uridine diphosphate glucose through UTP--glucose-1-phosphate uridylyltransferase. The product, uridine diphosphate glucose, can undergo a reversible reaction in which it can be turned into uridine diphosphategalactose through an UDP-glucose 4-epimerase, and so the cycle can keep going as long as more lactose or galactose is imported into the cell.

The synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate. N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound can either be isomerized or deaminated into Beta-D-fructofuranose 6-phosphate through a glucosamine-fructose-6-phosphate aminotransferase and a glucosamine-6-phosphate deaminase respectively. Glucosamine 6-phosphate undergoes a reversible reaction to glucosamine 1 phosphate through a phosphoglucosamine mutase. This compound is then acetylated through a bifunctional protein glmU to produce a N-Acetyl glucosamine 1-phosphate. N-Acetyl glucosamine 1-phosphate enters the nucleotide sugar synthesis by reacting with UTP and hydrogen ion through a bifunctional protein glmU releasing pyrophosphate and a Uridine diphosphate-N-acetylglucosamine.This compound can either be isomerized into a UDP-N-acetyl-D-mannosamine or undergo a reaction with phosphoenolpyruvic acid through UDP-N-acetylglucosamine 1-carboxyvinyltransferase releasing a phosphate and a UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate. UDP-N-acetyl-D-mannosamine undergoes a NAD dependent dehydrogenation through a UDP-N-acetyl-D-mannosamine dehydrogenase, releasing NADH, a hydrogen ion and a UDP-N-Acetyl-alpha-D-mannosaminuronate, This compound is then used in the production of enterobacterial common antigens. UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate is reduced through a NADPH dependent UDP-N-acetylenolpyruvoylglucosamine reductase, releasing a NADP and a UDP-N-acetyl-alpha-D-muramate. This compound is involved in the D-glutamine and D-glutamate metabolism.

The biosynthesis of phosphoribosyl pyrophosphate begins as a product of the pentose phosphate and D-ribose 5-phosphate interaction. When catalyzed with a phosphopentomutase, the product is a ribose 1-phosphate. Ribose 1-phosphate can interact spontaneously with ATP resulting in a release of hydrogen ion, ADP and a ribose 1,5-biphosphate. Ribose 1,5-biphosphate is then phosphorylated through a ribose 1,5-bisphosphokinase resulting in the release of ADP and phosphoribosyl pyrophosphate. Phosphoribosyl pyrophosphate will then participate in the purine nucleotides de novo biosynthesis pathway. Alternatively pentose phosphate and D-ribose 5-phosphate's interaction can be phosphorylated through an ATP driven ribose-phosphate diphosphokinase resulting in a release of a hydrogen ion, an AMP and a phosphoribosyl pyrophosphate which will again participate in the purine nucleotides de novo biosynthesis pathway.

The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway