Pathways

Lysine is biosynthesized from L-aspartic acid. L-Aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate/orotate:H+ symporter, glutamate/aspartate:H+ symporter GltP, dicarboxylate transporter, C4 dicarboxylate/C4 monocarboxylate transporter DauA, and glutamate/aspartate ABC transporter. L-Aspartic acid is phosphorylated by an ATP-driven aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-Aspartyl-4-phosphate is then dehydrogenated through an NADPH-driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP, and L-aspartic 4-semialdehyde (involved in methionine biosynthesis). L-Aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water, and (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH-driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP, and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through an N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid and N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through an N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglycan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine. L-Lysine is then incorporated into the lysine degradation pathway. Lysine also regulates its own biosynthesis by repressing dihydrodipicolinate synthase and also by repressing lysine-sensitive aspartokinase 3. Diaminopielate is a precursor for lysine as well as other cell wall components. Synthesis of lysine starts by converting L-aspartic acid (L-aspartate) to L-Aspartyl-4-phosphate by aspartate kinase. L-Aspartyl-4-phosphate transforms to form L-aspartic 4-semialdehyde (L-aspartate semialdehyde) by aspartate semialdehyde dehydrogenase with NADPH. L-aspartic 4-semialdehyde can start the metabolic pathway of synthesis of methionine as well as synthesis of threonine. Aspartate kinase can be regulated by its end product: L-Lysine.

Lysine is biosynthesized from L-aspartic acid. L-Aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate/orotate:H+ symporter, glutamate/aspartate:H+ symporter GltP, dicarboxylate transporter, C4 dicarboxylate/C4 monocarboxylate transporter DauA, and glutamate/aspartate ABC transporter. L-Aspartic acid is phosphorylated by an ATP-driven aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-Aspartyl-4-phosphate is then dehydrogenated through an NADPH-driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP, and L-aspartic 4-semialdehyde (involved in methionine biosynthesis). L-Aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water, and (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH-driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP, and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through an N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid and N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through an N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglycan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine. L-Lysine is then incorporated into the lysine degradation pathway. Lysine also regulates its own biosynthesis by repressing dihydrodipicolinate synthase and also by repressing lysine-sensitive aspartokinase 3. Diaminopielate is a precursor for lysine as well as other cell wall components. Synthesis of lysine starts by converting L-aspartic acid (L-aspartate) to L-Aspartyl-4-phosphate by aspartate kinase. L-Aspartyl-4-phosphate transforms to form L-aspartic 4-semialdehyde (L-aspartate semialdehyde) by aspartate semialdehyde dehydrogenase with NADPH. L-aspartic 4-semialdehyde can start the metabolic pathway of synthesis of methionine as well as synthesis of threonine. Aspartate kinase can be regulated by its end product: L-Lysine.

The degradation of L-lysine happens in liver and it is consisted of seven reactions. L-Lysine is imported into liver through low affinity cationic amino acid transporter 2 (cationic amino acid transporter 2/SLC7A2). Afterwards, L-lysine is imported into mitochondria via mitochondrial ornithine transporter 2. L-Lysine can also be obtained from biotin metabolism. L-Lysine and oxoglutaric acid will be combined to form saccharopine by facilitation of mitochondrial alpha-aminoadipic semialdehyde synthase, and then, mitochondrial alpha-aminoadipic semialdehyde synthase will further breaks saccharopine down to allysine and glutamic acid. Allysine will be degraded to form aminoadipic acid through alpha-aminoadipic semialdehyde dehydrogenase. Oxoadipic acid is formed from catalyzation of mitochondrial kynurenine/alpha-aminoadipate aminotransferase on aminoadipic acid. Oxoadipic acid will be further catalyzed to form glutaryl-CoA, and glutaryl-CoA converts to crotonoyl-CoA, and crotonoyl-CoA transformed to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA will form Acetyl-CoA as the final product through the intermediate compound: acetoacetyl-CoA. Acetyl-CoA will undergo citric acid cycle metabolism. Carnitine is another key byproduct of lysine metabolism (not shown in this pathway).

The degradation of L-lysine happens in liver and it is consisted of seven reactions. L-Lysine is imported into liver through low affinity cationic amino acid transporter 2 (cationic amino acid transporter 2/SLC7A2). Afterwards, L-lysine is imported into mitochondria via mitochondrial ornithine transporter 2. L-Lysine can also be obtained from biotin metabolism. L-Lysine and oxoglutaric acid will be combined to form saccharopine by facilitation of mitochondrial alpha-aminoadipic semialdehyde synthase, and then, mitochondrial alpha-aminoadipic semialdehyde synthase will further breaks saccharopine down to allysine and glutamic acid. Allysine will be degraded to form aminoadipic acid through alpha-aminoadipic semialdehyde dehydrogenase. Oxoadipic acid is formed from catalyzation of mitochondrial kynurenine/alpha-aminoadipate aminotransferase on aminoadipic acid. Oxoadipic acid will be further catalyzed to form glutaryl-CoA, and glutaryl-CoA converts to crotonoyl-CoA, and crotonoyl-CoA transformed to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA will form Acetyl-CoA as the final product through the intermediate compound: acetoacetyl-CoA. Acetyl-CoA will undergo citric acid cycle metabolism. Carnitine is another key byproduct of lysine metabolism (not shown in this pathway).

The degradation of L-lysine happens in liver and it is consisted of seven reactions. L-Lysine is imported into liver through low affinity cationic amino acid transporter 2 (cationic amino acid transporter 2/SLC7A2). Afterwards, L-lysine is imported into mitochondria via mitochondrial ornithine transporter 2. L-Lysine can also be obtained from biotin metabolism. L-Lysine and oxoglutaric acid will be combined to form saccharopine by facilitation of mitochondrial alpha-aminoadipic semialdehyde synthase, and then, mitochondrial alpha-aminoadipic semialdehyde synthase will further breaks saccharopine down to allysine and glutamic acid. Allysine will be degraded to form aminoadipic acid through alpha-aminoadipic semialdehyde dehydrogenase. Oxoadipic acid is formed from catalyzation of mitochondrial kynurenine/alpha-aminoadipate aminotransferase on aminoadipic acid. Oxoadipic acid will be further catalyzed to form glutaryl-CoA, and glutaryl-CoA converts to crotonoyl-CoA, and crotonoyl-CoA transformed to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA will form Acetyl-CoA as the final product through the intermediate compound: acetoacetyl-CoA. Acetyl-CoA will undergo citric acid cycle metabolism. Carnitine is another key byproduct of lysine metabolism (not shown in this pathway).

The degradation of L-lysine happens in liver and it is consisted of seven reactions. L-Lysine is imported into liver through low affinity cationic amino acid transporter 2 (cationic amino acid transporter 2/SLC7A2). Afterwards, L-lysine is imported into mitochondria via mitochondrial ornithine transporter 2. L-Lysine can also be obtained from biotin metabolism. L-Lysine and oxoglutaric acid will be combined to form saccharopine by facilitation of mitochondrial alpha-aminoadipic semialdehyde synthase, and then, mitochondrial alpha-aminoadipic semialdehyde synthase will further breaks saccharopine down to allysine and glutamic acid. Allysine will be degraded to form aminoadipic acid through alpha-aminoadipic semialdehyde dehydrogenase. Oxoadipic acid is formed from catalyzation of mitochondrial kynurenine/alpha-aminoadipate aminotransferase on aminoadipic acid. Oxoadipic acid will be further catalyzed to form glutaryl-CoA, and glutaryl-CoA converts to crotonoyl-CoA, and crotonoyl-CoA transformed to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA will form Acetyl-CoA as the final product through the intermediate compound: acetoacetyl-CoA. Acetyl-CoA will undergo citric acid cycle metabolism. Carnitine is another key byproduct of lysine metabolism (not shown in this pathway).

Lysine is an essential amino acid used in protein synthesis. Lysine can be transported into the cell by probable cadaverine (also known as lysine antiporter). Once inside the cell, lysine is decarboxylated by lysine decarboxylase to cadaverine. Cadaverine can then exit the cell via the same type of transporter as lysine (probable cadaverine). Alternatively, lysine can be produced during lysine biosynthesis (from aspartic acid) inside the cell and used in the same pathway.