Pathways

Kynurenine is an indole uremic toxin compound that is formed through metabolism from dietary tryptophan in liver hepatic cells. After being transported into a hepatocyte from portal circulation the amino acid tryptophan undergoes a reaction with the enzyme tryptophan-2,3-dioxygenase to form kynurenine. When this compound enters into systemic circulation it is shown to be a major uremic toxin when high levels of it are retained in the blood and not excreted in urine. Kynurenine is shown to activate aryl hydrocarbon receptors that can lead to renal impairment, and it also disrupts the electron transport chain and oxidative phosphorylation causing muscle atrophy.

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.

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.

L-alanine metabolized from pyruvate and glutamate reacting through a Alanine aminotransferase resulting in the release of a oxoglutaric acid and a alanine. Alanine is degraded by alanine aminotransferase to form pyruvic acid. Meanwhile, oxoglutaric acid is converted to L-glutamic acid also by alanine aminotransferase. Pyruvate is transported into mitochondria for further metabolism.

L-arabinose enters E. coli unphosphorylated via a low-affinity proton-driven transporter (AraE) or a high-affinity ATP-driven system (AraFGH). Following entry, it is converted to L-ribulose-5-phosphate by an isomerase and kinase. L-ribulose-5-phosphate is then converted by an epimerase to the pentose phosphate pathway intermediate, D-xylulose-5-phosphate. D-xylulose-5-phosphate then enters metabolism pathways to become precursor metabolites, reducing power and metabolic energy.

L-arabinose enters E. coli unphosphorylated via a low-affinity proton-driven transporter (AraE) or a high-affinity ATP-driven system (AraFGH). Following entry, it is converted to L-ribulose-5-phosphate by an isomerase and kinase. L-ribulose-5-phosphate is then converted by an epimerase to the pentose phosphate pathway intermediate, D-xylulose-5-phosphate. D-xylulose-5-phosphate then enters metabolism pathways to become precursor metabolites, reducing power and metabolic energy.

L-arabinose enters E. coli unphosphorylated via a low-affinity proton-driven transporter (AraE) or a high-affinity ATP-driven system (AraFGH). Following entry, it is converted to L-ribulose-5-phosphate by an isomerase and kinase. L-ribulose-5-phosphate is then converted by an epimerase to the pentose phosphate pathway intermediate, D-xylulose-5-phosphate. D-xylulose-5-phosphate then enters metabolism pathways to become precursor metabolites, reducing power and metabolic energy.

L-arabinose enters E. coli unphosphorylated via a low-affinity proton-driven transporter (AraE) or a high-affinity ATP-driven system (AraFGH). Following entry, it is converted to L-ribulose-5-phosphate by an isomerase and kinase. L-ribulose-5-phosphate is then converted by an epimerase to the pentose phosphate pathway intermediate, D-xylulose-5-phosphate. D-xylulose-5-phosphate then enters metabolism pathways to become precursor metabolites, reducing power and metabolic energy.