Browsing Pathways

Nicotinamide adenine dinucleotide (NAD) can be biosynthesized from L-aspartic acid. This amino acid reacts with oxygen through an L-aspartate oxidase resulting in a hydrogen ion, hydrogen peroxide and an iminoaspartic acid. The latter compound interacts with dihydroxyacetone phosphate through a quinolinate synthase A, resulting in a phosphate, water, and a quinolic acid. Quinolic acid interacts with phosphoribosyl pyrophosphate and hydrogen ion through a quinolinate phosphoribosyltransferase resulting in pyrophosphate, carbon dioxide and nicotinate beta-D-ribonucleotide. The latter is adenylated through an ATP driven nicotinate-mononucleotide adenylyltransferase releasing a pyrophosphate and resulting in a nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide is processed through an NAD synthetase, NH3-dependent in two different manners. In the first case, Nicotinic acid adenine dinucleotide interacts with ATP, L-glutamine and water through the enzyme and results in hydrogen ion, AMP, pyrophosphate, L-glutamic acid and NAD. In the second case, Nicotinic acid adenine dinucleotide interacts with ATP and ammonium through the enzyme resulting in a pyrophosphate, AMP, hydrogen ion and NAD. NAD then proceeds to regulate its own pathway by repressing L-aspartate oxidase. As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate , while in eukaryotes, the de novo pathway starts with tryptophan.

The metabolism of 1-Acyl-sn-glycero-3-phosphoethanolamine compounds represents a tightly coordinated sequence of biosynthetic and degradative processes that connect lipid metabolism with central carbon pathways such as glycolysis. The pathway typically begins with the formation of glycerol 3-phosphate, generated through the NADPH-dependent reduction of dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase, linking the lipid pathway to glycolytic intermediates. This glycerol 3-phosphate then serves as a foundational scaffold for phospholipid biosynthesis. In the first acylation step, glycerol-3-phosphate acyltransferase transfers an acyl group from a corresponding acyl-CoA (such as lauroyl-, myristoyl-, or palmitoyl-CoA) to the sn-1 position, producing a lysophosphatidic acid (LysoPA) species. A second acyl chain, typically unsaturated, is added at the sn-2 position by 1-acylglycerol-3-phosphate O-acyltransferase, forming a fully acylated phosphatidic acid (PA). This PA is then activated by CDP-diglyceride synthetase using cytidine triphosphate (CTP) to yield CDP-diacylglycerol (CDP-DG), a key intermediate in the biosynthesis of phospholipids. Through the action of phosphatidylserine synthase, L-serine is incorporated to form phosphatidylserine (PS), which is subsequently decarboxylated by phosphatidylserine decarboxylase to produce phosphatidylethanolamine (PE). This PE can then undergo N-acylation of its ethanolamine headgroup, catalyzed by phospholipase A1, which transfers an additional acyl group (often saturated) from an acyl-CoA to form 1-Acyl-sn-glycero-3-phosphoethanolamine (N-acyl-PE). At this point, the N-acyl-PE molecule may function as a membrane-associated signaling or structural lipid. However, it can also be routed back into central metabolism. Glycerophosphoryl diester phosphodiesterase hydrolyzes the compound to yield 1-acyl-sn-glycerol 3-phosphate, ethanolamine, and a proton. The liberated ethanolamine is further catabolized by ethanolamine ammonia-lyase, which converts it into acetaldehyde and ammonia. Acetaldehyde is then oxidized by acetaldehyde dehydrogenase in the presence of NAD⁺ and Coenzyme A to form acetyl-CoA, a core metabolic intermediate that feeds directly into the TCA cycle or glycolysis via the acetyl-CoA.

Glycolic acid is introduced into the cytoplasm through either a glycolate / lactate:H+ symporter or a acetate / glycolate transporter. Once inside, glycolic acid reacts with an oxidized electron-transfer flavoprotein through a glycolate oxidase resulting in a reduced acceptor and glyoxylic acid. Glyoxylic acid can also be obtained from the introduction of glyoxylic acid. It can also be obtained from the metabolism of (S)-allantoin. S-allantoin is introduced into the cytoplasm through a purine and pyrimidine transporter(allantoin specific). Once inside, the compound reacts with water through a allantoinase resulting in hydrogen ion and allantoic acid. Allantoic acid then reacts with water and hydrogen ion through a allantoate amidohydrolase resulting in a carbon dioxide, ammonium and S-ureidoglycine. The latter compound reacts with water through a S-ureidoglycine aminohydrolase resulting in ammonium and S-ureidoglycolic acid which in turn reacts with a Ureidoglycolate lyase resulting in urea and glyoxylic acid. Glyoxylic acid can either be metabolized into L-malic acid by a reaction with acetyl-CoA and Water through a malate synthase G which also releases hydrogen ion and Coenzyme A. L-malic acid is then incorporated into the TCA cycle. Glyoxylic acid can also be metabolized by glyoxylate carboligase, releasing a carbon dioxide and tartronate semialdehyde. The latter compound is then reduced by an NADH driven tartronate semialdehyde reductase 2 resulting in glyceric acid. Glyceric acid is phosphorylated by a glycerate kinase 2 resulting in a 3-phosphoglyceric acid. This compound is then integrated into various other pathways: cysteine biosynthesis, serine biosynthesis and glycolysis and pyruvate dehydrogenase.

The metabolism of 1-Acyl-sn-glycero-3-phosphoethanolamine compounds represents a tightly coordinated sequence of biosynthetic and degradative processes that connect lipid metabolism with central carbon pathways such as glycolysis. The pathway typically begins with the formation of glycerol 3-phosphate, generated through the NADPH-dependent reduction of dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase, linking the lipid pathway to glycolytic intermediates. This glycerol 3-phosphate then serves as a foundational scaffold for phospholipid biosynthesis. In the first acylation step, glycerol-3-phosphate acyltransferase transfers an acyl group from a corresponding acyl-CoA (such as lauroyl-, myristoyl-, or palmitoyl-CoA) to the sn-1 position, producing a lysophosphatidic acid (LysoPA) species. A second acyl chain, typically unsaturated, is added at the sn-2 position by 1-acylglycerol-3-phosphate O-acyltransferase, forming a fully acylated phosphatidic acid (PA). This PA is then activated by CDP-diglyceride synthetase using cytidine triphosphate (CTP) to yield CDP-diacylglycerol (CDP-DG), a key intermediate in the biosynthesis of phospholipids. Through the action of phosphatidylserine synthase, L-serine is incorporated to form phosphatidylserine (PS), which is subsequently decarboxylated by phosphatidylserine decarboxylase to produce phosphatidylethanolamine (PE). This PE can then undergo N-acylation of its ethanolamine headgroup, catalyzed by phospholipase A1, which transfers an additional acyl group (often saturated) from an acyl-CoA to form 1-Acyl-sn-glycero-3-phosphoethanolamine (N-acyl-PE). At this point, the N-acyl-PE molecule may function as a membrane-associated signaling or structural lipid. However, it can also be routed back into central metabolism. Glycerophosphoryl diester phosphodiesterase hydrolyzes the compound to yield 1-acyl-sn-glycerol 3-phosphate, ethanolamine, and a proton. The liberated ethanolamine is further catabolized by ethanolamine ammonia-lyase, which converts it into acetaldehyde and ammonia. Acetaldehyde is then oxidized by acetaldehyde dehydrogenase in the presence of NAD⁺ and Coenzyme A to form acetyl-CoA, a core metabolic intermediate that feeds directly into the TCA cycle or glycolysis via the acetyl-CoA.

The metabolism of 1-Acyl-sn-glycero-3-phosphoethanolamine compounds represents a tightly coordinated sequence of biosynthetic and degradative processes that connect lipid metabolism with central carbon pathways such as glycolysis. The pathway typically begins with the formation of glycerol 3-phosphate, generated through the NADPH-dependent reduction of dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase, linking the lipid pathway to glycolytic intermediates. This glycerol 3-phosphate then serves as a foundational scaffold for phospholipid biosynthesis. In the first acylation step, glycerol-3-phosphate acyltransferase transfers an acyl group from a corresponding acyl-CoA (such as lauroyl-, myristoyl-, or palmitoyl-CoA) to the sn-1 position, producing a lysophosphatidic acid (LysoPA) species. A second acyl chain, typically unsaturated, is added at the sn-2 position by 1-acylglycerol-3-phosphate O-acyltransferase, forming a fully acylated phosphatidic acid (PA). This PA is then activated by CDP-diglyceride synthetase using cytidine triphosphate (CTP) to yield CDP-diacylglycerol (CDP-DG), a key intermediate in the biosynthesis of phospholipids. Through the action of phosphatidylserine synthase, L-serine is incorporated to form phosphatidylserine (PS), which is subsequently decarboxylated by phosphatidylserine decarboxylase to produce phosphatidylethanolamine (PE). This PE can then undergo N-acylation of its ethanolamine headgroup, catalyzed by phospholipase A1, which transfers an additional acyl group (often saturated) from an acyl-CoA to form 1-Acyl-sn-glycero-3-phosphoethanolamine (N-acyl-PE). At this point, the N-acyl-PE molecule may function as a membrane-associated signaling or structural lipid. However, it can also be routed back into central metabolism. Glycerophosphoryl diester phosphodiesterase hydrolyzes the compound to yield 1-acyl-sn-glycerol 3-phosphate, ethanolamine, and a proton. The liberated ethanolamine is further catabolized by ethanolamine ammonia-lyase, which converts it into acetaldehyde and ammonia. Acetaldehyde is then oxidized by acetaldehyde dehydrogenase in the presence of NAD⁺ and Coenzyme A to form acetyl-CoA, a core metabolic intermediate that feeds directly into the TCA cycle or glycolysis via the acetyl-CoA.

The metabolism of 1-Acyl-sn-glycero-3-phosphoethanolamine compounds represents a tightly coordinated sequence of biosynthetic and degradative processes that connect lipid metabolism with central carbon pathways such as glycolysis. The pathway typically begins with the formation of glycerol 3-phosphate, generated through the NADPH-dependent reduction of dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase, linking the lipid pathway to glycolytic intermediates. This glycerol 3-phosphate then serves as a foundational scaffold for phospholipid biosynthesis. In the first acylation step, glycerol-3-phosphate acyltransferase transfers an acyl group from a corresponding acyl-CoA (such as lauroyl-, myristoyl-, or palmitoyl-CoA) to the sn-1 position, producing a lysophosphatidic acid (LysoPA) species. A second acyl chain, typically unsaturated, is added at the sn-2 position by 1-acylglycerol-3-phosphate O-acyltransferase, forming a fully acylated phosphatidic acid (PA). This PA is then activated by CDP-diglyceride synthetase using cytidine triphosphate (CTP) to yield CDP-diacylglycerol (CDP-DG), a key intermediate in the biosynthesis of phospholipids. Through the action of phosphatidylserine synthase, L-serine is incorporated to form phosphatidylserine (PS), which is subsequently decarboxylated by phosphatidylserine decarboxylase to produce phosphatidylethanolamine (PE). This PE can then undergo N-acylation of its ethanolamine headgroup, catalyzed by phospholipase A1, which transfers an additional acyl group (often saturated) from an acyl-CoA to form 1-Acyl-sn-glycero-3-phosphoethanolamine (N-acyl-PE). At this point, the N-acyl-PE molecule may function as a membrane-associated signaling or structural lipid. However, it can also be routed back into central metabolism. Glycerophosphoryl diester phosphodiesterase hydrolyzes the compound to yield 1-acyl-sn-glycerol 3-phosphate, ethanolamine, and a proton. The liberated ethanolamine is further catabolized by ethanolamine ammonia-lyase, which converts it into acetaldehyde and ammonia. Acetaldehyde is then oxidized by acetaldehyde dehydrogenase in the presence of NAD⁺ and Coenzyme A to form acetyl-CoA, a core metabolic intermediate that feeds directly into the TCA cycle or glycolysis via the acetyl-CoA.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

The metabolism of 1-Acyl-sn-glycero-3-phosphoethanolamine compounds represents a tightly coordinated sequence of biosynthetic and degradative processes that connect lipid metabolism with central carbon pathways such as glycolysis. The pathway typically begins with the formation of glycerol 3-phosphate, generated through the NADPH-dependent reduction of dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase, linking the lipid pathway to glycolytic intermediates. This glycerol 3-phosphate then serves as a foundational scaffold for phospholipid biosynthesis. In the first acylation step, glycerol-3-phosphate acyltransferase transfers an acyl group from a corresponding acyl-CoA (such as lauroyl-, myristoyl-, or palmitoyl-CoA) to the sn-1 position, producing a lysophosphatidic acid (LysoPA) species. A second acyl chain, typically unsaturated, is added at the sn-2 position by 1-acylglycerol-3-phosphate O-acyltransferase, forming a fully acylated phosphatidic acid (PA). This PA is then activated by CDP-diglyceride synthetase using cytidine triphosphate (CTP) to yield CDP-diacylglycerol (CDP-DG), a key intermediate in the biosynthesis of phospholipids. Through the action of phosphatidylserine synthase, L-serine is incorporated to form phosphatidylserine (PS), which is subsequently decarboxylated by phosphatidylserine decarboxylase to produce phosphatidylethanolamine (PE). This PE can then undergo N-acylation of its ethanolamine headgroup, catalyzed by phospholipase A1, which transfers an additional acyl group (often saturated) from an acyl-CoA to form 1-Acyl-sn-glycero-3-phosphoethanolamine (N-acyl-PE). At this point, the N-acyl-PE molecule may function as a membrane-associated signaling or structural lipid. However, it can also be routed back into central metabolism. Glycerophosphoryl diester phosphodiesterase hydrolyzes the compound to yield 1-acyl-sn-glycerol 3-phosphate, ethanolamine, and a proton. The liberated ethanolamine is further catabolized by ethanolamine ammonia-lyase, which converts it into acetaldehyde and ammonia. Acetaldehyde is then oxidized by acetaldehyde dehydrogenase in the presence of NAD⁺ and Coenzyme A to form acetyl-CoA, a core metabolic intermediate that feeds directly into the TCA cycle or glycolysis via the acetyl-CoA.