Browsing Pathways

The lac operon in E. coli produces three proteins that are used to metabolize lactose in the absence of glucose. If glucose is present in the cell, cAMP levels will be low, and only a small amount will be able to bind to the cAMP-activated global transcriptional regulator (CRP or CAP). Without cAMP bound, the protein is unactivated, and cannot bind to the activator binding site of the operon. However, when glucose levels are low, cAMP levels are higher, and more can bind to and activate CRP, allowing it to activate the operon. At the same time, if lactose levels in the cell are low, there will be minimal amounts of allolactose produced by any beta-galactosidase present currently in the cell. Allolactose is necessary to bind to the lactose operon repressor, and without allolactose bound to the repressor, it is tightly bound to the operator region of the operon. However, when concentrations of lactose are higher in the cell, more allolactose is produced, and when it binds to the repressor, the repressor cannot bind to the operator, freeing it and allowing RNA polymerase to bind. This, combined with the binding of the CRP protein to the activator binding site leads to all three genes in the operon being transcribed. The first gene, lacZ, encodes the protein beta-galactosidase, an enzyme that hydrolyzes beta-galactosides into monosaccharides. In this instance, it hydrolyzes lactose into glucose and galactose. In some cases, it can also cause the isomerization of lactose into allolactose. The second gene, lacY, encodes the protein lactose permease, which is a transport protein that pumps lactose into the cell by using a proton gradient that also flows into the cell. Finally, the last gene, lacA, encodes the protein galactoside O-acetyltransferase, an enzyme that catalyzes the transfer of the acetyl group of acetyl-CoA to beta-galactosides. This specific protein is not known to be important to the lac operon, but may be important in detoxifying the bacteria by preventing acetylated galactosides from re-entering the cell.

The degradation of propanoyl-CoA starts with propanoyl-CoA undergoing a decarboxylase reaction by reacting with hydrogen carbonate and ATP resulting in the release of a phosphate, an ADP, a hydrogen ion and an S-methylmalonyl-CoA. This compound in turn reacts through an epimerase reaction resulting in the release of a R-methylmalonyl-CoA. This compound in turn can undergo a reversible reaction through a methylmalonyl-CoA mutase resulting in the release of a succinyl-CoA. This compound can be converted back to R-methylmalonyl-CoA through a methylmalonyl-CoA mutase. Methylmalonyl-CoA can then be converted into propanoyl-CoA through a methylmalonyl CoA decarboxylase . This compound in turn reacts with a succinate through a propionyl-CoA succinate CoA transferase resulting in the release of a propanoate and a succinyl-CoA.

The pathway begins with the introduction of deoxycytidine into the cytosol, either through a nupG symporter or a nupC symporter. Once inside it is deaminated when reacting with a water molecule, a hydrogen ion and a deoxycytidine deaminase resulting in the release of an ammonium and a deoxyuridine. Deoxyuridine can also be imported through a nupG symporter or a nupC symporter. Deoxyuridine can react with an ATP through a deoxyuridine kinase resulting in the release of a ADP , a hydrogen ion and a dUMP. Deoxyuridine can also react with a phosphate through a uracil phosphorylase resulting in the release of a uracil and a deoxy-alpha-D-ribose 1-phosphate. This compound in turn reacts with a thymine through a thymidine phosphorylase resulting in the release of a phosphate and a thymidine. Thymidine in turn reacts with an ATP through a thymidine kinase resulting in a release of an ADP, a hydrogen ion and a dTMP

This pathway demonstrates the degradation of extracellular putrescine in E.coli. Putrescine is imported by putrescine transporter (encoded by puuP gene). Putrescine is γ-glutamylated by activation of ATP which generates γ-glutamyl-putrescine, phosphate, and ADP. γ-glutamyl-putrescine is oxidized by gamma-glutamylputrescine oxidoreductase to form γ-glutamyl-γ-butyraldehyde, also produce ammonium and water. Gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase dehydrogenates γ-glutamyl-γ-butyraldehyde to γ-glutamyl-γ-aminobutyrate, which is then dehydrogenated into γ-Aminobutyric acid and L-Glutamic acid by γ-glutamyl-γ-aminobutyrate hydrolase.

Most bacteria, including Escherichia coli, are composed of murein which protects and stabilizes the cell wall. Over half of the murein is broken down by Escherichia coli and recycled for the next generation. The main muropeptide is GlcNAc-anhydro-N-acetylmuramic acid (anhMurNAc)-l-Ala-γ-d-Glu-meso-Dap-d-Ala which enters the cytoplasm by AmpG protein. The peptide is then released from the muropeptide. 1,6-Anhydro-N-acetylmuramic acid (anhMurNAc) is recycled by its conversion to N-acetylglucosamine-phosphate (GlcNAc-P). The sugar is phosphorylated by anhydro-N-acetylmuramic acid kinase (AnmK) to produce MurNAc-P. Etherase cleaves MurNAc-P to produce N-acetyl-D-glucosamine 6-phosphate. The product can undergo further degradation or be recycled into peptidoglycan monomers. The pathway's final product is a peptidoglycan biosynthesis precursor, UDP-N-acetyl-α-D-muramate. The enzyme muropeptide ligase (mpl), attaches the recovered Ala-Glu-DAP tripeptide to the precursor UDP-N-acetyl-α-D-muramate to return to the peptide to the peptidoglycan biosynthetic pathway to synthesize the cell wall.

The salvage of adenine begins with adenine being transporter into the cytosol through a adeP hydrogen symporter. Once in the cytosol adenine is degraded by reacting with a ribose-1-phosphate through an adenosine phosphorylase resulting in the release of a phosphate and adenosine. Adenosine is then deaminated by reacting with water, a hydrogen ion and an adenosine deaminase resulting in the release of an ammonium and a inosine . Inosine then reacts with a phosphate through a inosine phosphorylase resulting in the release of a ribose 1-phosphate and a hypoxanthine. Hypoxanthine reacts with a PRPP through a hypoxanthine phosphoribosyltransferase resulting in the release of a pyrophosphate and a IMP molecule.

The degradation of propanoyl-CoA starts with propanoyl-CoA undergoing a decarboxylase reaction by reacting with hydrogen carbonate and ATP resulting in the release of a phosphate, an ADP, a hydrogen ion and an S-methylmalonyl-CoA. This compound in turn reacts through an epimerase reaction resulting in the release of a R-methylmalonyl-CoA. This compound in turn can undergo a reversible reaction through a methylmalonyl-CoA mutase resulting in the release of a succinyl-CoA. This compound can be converted back to R-methylmalonyl-CoA through a methylmalonyl-CoA mutase. Methylmalonyl-CoA can then be converted into propanoyl-CoA through a methylmalonyl CoA decarboxylase . This compound in turn reacts with a succinate through a propionyl-CoA succinate CoA transferase resulting in the release of a propanoate and a succinyl-CoA.

Fructosamines are compounds that result from glycation reactions between a sugar and a primary amine, followed by isomerization via the Amadori rearrangement. In fructoselysine degradation, fructoselysine firstly converts to 1-[(5-Amino-5-carboxypentyl)amino]-1-deoxyfructose by protein frlC, and then 1-[(5-Amino-5-carboxypentyl)amino]-1-deoxyfructose is transformed to fructoselysine-6-phosphate by fructoselysine kinase which is powered by ATP. Fructoselysine-6-phosphate finally degrades to β-D-Glucose 6-phosphate and L-lysine by fructoselysine 6-phosphate deglycase.

The degradation of N-acetylneuraminate begins with its incorporation into the cytosol through a hydrogen symporter. Once inside the cytosol it is degraded by a N-acetylneuraminate lyase resulting in a release of a pyruvic acid and N-acetymannosamine. The latter compound is phosphorylated by an ATP driven N-Acetylmannosamine kinase resulting in the release of an ADP, a hydrogen ion and a N-Acetyl-D-mannosamine 6-phosphate. This phosphorylated compound is then metabolized by a putative N-acetylmannosamine-6-phosphate 2-epimerase resulting in the release of a N-Acetyl-D-glucosamine 6-phosphate. This compound is then deacetylated through a N-acetylglucosamine-6-phosphate deacetylase resulting in the release of an Acetic acid and a glucosamine 6-phosphate This compound can then be deaminated through a glucosamine-6-phosphate deaminase resulting in the release of an ammonium and a beta-D-fructofuranose 6-phosphate which can then be incorporated into the glycolysis pathway.

ADP-L-glycero-β-D-manno-heptose is a precursor for the inner core lipopolysaccharide (LPS), which is the outer membrane of Gram-negative bacteria. LPS is consisted of lipid A, a core oligosaccharide, and an O-specific polysaccharide (O antigen). This biosynthesis pathway starts with catalyzation of D-sedoheptulose 7-phosphate that produced from pentose phosphate pathway to form D-glycero-D-manno-heptose 7-phosphate by lysophospholipid acyltransferase. D-glycero-D-manno-heptose 7-phosphate later undergoes catalyze to form D-glycero-β-D-manno-heptose 1,7-bisphosphate by fused heptose 7-phosphate kinase (also known as heptose 1-phosphate adenyltransferase) that powered by ATP. D-glycero-β-D-manno-heptose 1,7-bisphosphate will go through hydrolysis by D,D-heptose 1,7-bisphosphate phosphatase to form D-glycero-β-D-manno-heptose 1-phosphate and a phosphate. D-glycero-β-D-manno-heptose 1-phosphate will form ADP-D-Glycero-D-manno-heptose and diphosphate, and eventually ADP-D-Glycero-D-manno-heptose will be biotransformed to ADP-L-glycero-β-D-manno-heptose as the end product of this pathway by ADP-L-glycero-D-mannoheptose-6-epimerase.