Browsing Pathways

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.

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.

NAD molecules have a relatively short half-life. NAD can be degraded by enzymes, and the degraded NAD molecule can be recouped by NAD salvage cycles. NAD salvage cycles can be used for recycling degraded NAD products such as nicotinamide and nicotinamide D-ribonucleotide. NAD salvage cycles can also be used for absorption of exogenous NAD+. NAD reacts spontaneously with water resulting in the release of hydrogen ion, AMP and beta-nicotinamide D-ribonucleotide. This enzyme can either interact spontaneously with water resulting in the release of D-ribofuranose 5-phosphate, hydrogen ion and Nacinamide. On the other hand beta-nicotinamide D-ribonucleotide can also react with water through NMN amidohydrolase resulting in ammonium, and Nicotinate beta-D-ribonucleotide. Also it can interact with water spontaneously resulting in the release of phosphate resulting in a Nicotinamide riboside. Niacinamide interacts with water through a nicotinamidase resulting in a release of ammonium and nicotinic acid. Nicotinic acid interacts with water and phosphoribosyl pyrophosphate through an ATP driven nicotinate phosphoribosyltransferase resulting in the release of ADP, pyrophosphate and phosphate and nicotinate beta-D-ribonucleotide. Nicotinamide riboside interacts with an ATP driven NadR DNA-binding transcriptional repressor and NMN adenylyltransferase (Escherichia coli) resulting in a ADP, hydrogen ion and beta-nicotinamide D-ribonucleotide. The latter interacts with ATP and hydrogen ions through NadR DNA-binding transcriptional repressor and NMN adenylyltransferase resulting in pyrophosphate and NAD. Nicotinate beta-D-ribonucleotide is adenylated through the interaction with ATP and a hydrogen ion through a nicotinate-mononucleotide adenylyltransferase resulting in pyrophosphate and Nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide interacts with L-glutamine and water through an ATP driven NAD synthease, NH3-dependent resulting in AMP, pyrophosphate, hydrogen ion, L-glutamic acid and NAD.

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.

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.