Browsing Pathways

Vitamin B6 metabolism in bacteria involves the biosynthesis and utilization of various forms of Vitamin B6, primarily pyridoxal 5'-phosphate (PLP), the active form of the vitamin. Bacteria can synthesize Vitamin B6 through two main pathways: the de novo DXP-independent pathway (pyridoxal phosphate biosynthesis I) and the DXP-dependent pathway. In the de novo pathway, key enzymes like Pdx1 and Pdx2 convert intermediates into pyridoxine 5'-phosphate (PNP), which is then oxidized to PLP by the enzyme pyridoxine phosphate oxidase (PdxH). PLP acts as a cofactor for various enzymes involved in amino acid metabolism, including transaminases, decarboxylases, and racemases.Bacteria rely on PLP for critical cellular processes, including amino acid metabolism, stress response, and protection against oxidative damage.

Peptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor.In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space. The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compund and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl coa undergo acetylation throuhg a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein, follows catalyze the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase realeasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate. This compound undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate through a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, a phosphate and a UDP-N-acetylmuramoyl-L-alanine. This compound interacts with D-glutamic acid and ATP through UDP-N-acetylmuramoylalanine-D-glutamate ligase releasing ADP, A phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter compound then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine-diphosphoundecaprenol which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine.

Fructose metabolism begins with the transport of beta-D-glucose 6-phosphate through a glucose PTS permease. This compound is isomerized by a glucose-6-phosphate isomerase resulting in fructose 6-phosphate. This compound can be phosphorylated by two different enzymes: a pyridoxal phosphatase/fructose 1,6-bisphosphatase or an ATP-driven 6-phosphofructokinase-1, resulting in fructose 1,6-biphosphate. This compound can either react with a fructose bisphosphate aldolase class 1 resulting in D-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate or through a fructose biphosphate aldolase class 2 resulting in D-glyceraldehyde 3-phosphate. This compound can then either react in a reversible triosephosphate isomerase resulting in dihydroxyacetone phosphate or react with a phosphate through an NAD-dependent glyceraldehyde 3-phosphate dehydrogenase resulting in glyceric acid 1,3-biphosphate. This compound is dephosphorylated by a phosphoglycerate kinase resulting in 3-phosphoglyceric acid. This compound, in turn, can either react with a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase or a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase resulting in 2-phospho-D-glyceric acid. This compound interacts with an enolase resulting in a phosphoenolpyruvic acid and water. Phosphoenolpyruvic acid can react either through an AMP-driven phosphoenoylpyruvate synthase or an ADP-driven pyruvate kinase protein complex resulting in pyruvic acid. The pyruvic acid reacts with CoA through an NAD-driven pyruvate dehydrogenase complex resulting in carbon dioxide and an acetyl-CoA which gets incorporated into the TCA cycle pathway.

The citric acid cycle (also named tricarboxylic acid (TCA) cycle or the Krebs cycle), is a collection of 9 enzyme-catalyzed chemical reactions that occur in all living cells undergoing aerobic respiration. The citric acid cycle itself was officially identified in 1937 by Hans Adolf Krebs, who received the Nobel Prize for this discovery in 1953. In eukaryotes, the citric acid cycle occurs in the mitochondria. In prokaryotes, the TCA cycle occurs in the cytoplasm. The TCA cycle starts with acetyl-CoA, which is the “fuel” for the entire cycle. This important molecule comes from the breakdown of glycogen (a stored form of glucose), fats, and many amino acids. At beginning, acetyl-CoA first transfers its 2-carbon acetyl group to the 4-carbon acceptor compound called oxaloacetate to form the 6-carbon compound (citrate) for which the cycle is named. The resulting citrate will have numbers of chemical transformations, whereby it loses one carboxyl group (leading to the 5-carbon compound called alpha-ketoglutarate) and then a second carboxyl group (leading to the 4-carbon compound called succinate). Succinate molecule is further oxidized to fumarate, then malate and finally oxaloacetate. The regeneration of the 4-carbon oxaloacetate, allows the TCA cycle to continue. Oxidation step generates energy that is transferring energy-rich electrons for NAD+ to form NADH in TCA cycle. Each acetyl group will generate 3 NADH in TCA cycle.

The citric acid cycle (also named tricarboxylic acid (TCA) cycle or the Krebs cycle), is a collection of 9 enzyme-catalyzed chemical reactions that occur in all living cells undergoing aerobic respiration. The citric acid cycle itself was officially identified in 1937 by Hans Adolf Krebs, who received the Nobel Prize for this discovery in 1953. In eukaryotes, the citric acid cycle occurs in the mitochondria. In prokaryotes, the TCA cycle occurs in the cytoplasm. The TCA cycle starts with acetyl-CoA, which is the “fuel” for the entire cycle. This important molecule comes from the breakdown of glycogen (a stored form of glucose), fats, and many amino acids. At beginning, acetyl-CoA first transfers its 2-carbon acetyl group to the 4-carbon acceptor compound called oxaloacetate to form the 6-carbon compound (citrate) for which the cycle is named. The resulting citrate will have numbers of chemical transformations, whereby it loses one carboxyl group (leading to the 5-carbon compound called alpha-ketoglutarate) and then a second carboxyl group (leading to the 4-carbon compound called succinate). Succinate molecule is further oxidized to fumarate, then malate and finally oxaloacetate. The regeneration of the 4-carbon oxaloacetate, allows the TCA cycle to continue. Oxidation step generates energy that is transferring energy-rich electrons for NAD+ to form NADH in TCA cycle. Each acetyl group will generate 3 NADH in TCA cycle.

L-alanine is an essential component of proteins and peptidoglycan. The latter also contains about three molecules of D-alanine for every L-alanine. Only about 10 percent of the total alanine synthesized flows into peptidoglycan.There are at least 3 ways to begin the biosynthesis of alanine. The first method for alanine biosynthesis begins with L-cysteine produced from L-cysteine biosynthesis pathway. L-cysteine reacts with an [L-cysteine desulfurase] L-cysteine persulfide through a cysteine desulfurase resulting in a release of [L-cysteine desulfurase] l-cysteine persulfide and L-alanine. The second method starts with pyruvic acid reacting with L-glutamic acid through a glutamate-pyruvate aminotransferase resulting in a oxoglutaric acid and L-alanine. The third method starts with L-glutamic acid interacting with Alpha-ketoisovaleric acid through a valine transaminase resulting in an oxoglutaric acid and L-valine. L-valine reacts with pyruvic acid through a valine-pyruvate aminotransferase resulting Alpha-ketoisovaleric acid and L-alanine. This first step of the pathway, which can be catalyzed by either of two racemases (biosynthetic or catabolic), also serves an essential role in biosynthesis because its product, D-alanine, is an essential component of cell wall peptidoglycan (murein). D-alanine is metabolized by an ATP driven D-alanine ligase A and B resulting in D-alanyl-D-alanine. This product is incorporated into the peptidoglycan biosynthesis. L-alanine is metabolized with alanine racemase, either catabolic or metabolic resulting in a D-alanine. This compound reacts with water and a quinone through a D-amino acid dehydrogenase resulting in Pyruvic acid, hydroquinone and ammonium, thus entering the central metabolism and thereby can serve as a total source of carbon and energy. The role of the dadX racemase is degradative and dadX racemase can be induced by alanine and is subject to catabolite repression.

Glycolysis is a metabolic pathway consisting of ten reactions that convert glucose to pyruvate, releasing energy to form ATP and NADH. It occurs in two phases: the chemical priming phase and the energy-yielding phase. In the priming phase, D-glucose, which can be imported or derived from galactose metabolism, is phosphorylated to glucose-6-phosphate by a hexokinase-like enzyme, using ATP. This is then converted to fructose-6-phosphate, which is further phosphorylated to fructose-1,6-bisphosphate by 6-phosphofructokinase, also using ATP. Aldolase then splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which can interconvert via triosephosphate isomerase. In the energy-yielding phase, glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase, producing NADH in the process. ATP is generated when 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate. Further steps involve the conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase, followed by conversion to phosphoenolpyruvate by enolase. Finally, pyruvate kinase converts phosphoenolpyruvate to pyruvate, producing ATP in the process. Pyruvate then participates in further metabolic pathways, including pyruvate metabolism, tyrosine metabolism, and the synthesis of pantothenate and CoA.

Fatty acid oxidation is also known as beta-oxidation. Fatty acids are an important energy source because they are anhydrous and can be reduced. Fatty acids are good sources of energy as they yield more energy than carbohydrates. The fatty acid oxidation pathway degrades fatty acids into acetyl-CoA under anaerobic and aerobic conditions. Enzymes of this pathway can process short and long chain fatty acids. The first step in the pathway is the conversion of acyl-CoA to enoyl-CoA. The pathway continues in a cycle, each turn removing two carbon atoms from the input acyl-CoA to produce acetyl-CoA. Each turn also produces NADH.