Browsing Pathways

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.

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.

Histidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. The phosphoribosyl-ATP interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. The same enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. The product is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate, which reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. D-erythro-imidazole-glycerol-phosphate reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate. Next, imidazole acetol-phosphate reacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. Histidinal in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine. L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.

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.

This pathway shows the biosynthesis of methionine, which is an energy-costly process. Lysine biosynthesis produces L-Aspartate-semialdehyde, which later on is catalyzed to L-homoserine by bifunctional aspartokinase (also named homoserine dehydrogenase) 1 and 2. Homoserine is then activated by O-succinylation to form O-succinyl-L-homoserine via homoserine O-succinyltransferase (metA). Combining with L-cysteine, O-succinyl-L-homoserine form L-cystathionine and succinic acid by cystathionine gamma-synthase (metB). Cleavage of L-cystathionine by cystathionine beta-lyase (metC) or Protein MalY(as ) generates two small molecules: homocysteine and 2-aminoprop-2-enoate. Methionine synthase(MetH) or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase(MetE) will catalyzehomocysteine to form the final product: methionine. In E.coli, MetH can only function with existence of cobalamin (Vitamin B12), which can be available in the guy; without cobalamin, MetE will not be repressed so that it will catalyze the methionine. Methionine can be transported out of cell (into periplasmic space) by leucine efflux transporter.

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.