Pathways

Spermidine is formed from decarboxy-SAM and putrescine by catalyzing spermidine synthase (also knowns as polyamine aminopropyltransferase). The source of putrescine is transported from outside of cell by putrescine/spermidine ABC transporter. Decarboxy-SAM comes from S-Adenosylmethionine with catalyzation of adenosylmethionine decarboxylase and cofactors: pyruvic acid and magnesium. The other product of the aminopropyltransferase reaction is S-methyl-5'-thioadenosine (MTA), which can be recycled back to L-methionine in many organisms, but not in E. coli. Inhibition of E. coli adenosylmethionine decarboxylase by spermidine appears to be the most significant regulator of polyamine biosynthesis, probably limiting it when the intracellular spermidine concentration becomes excessive. In E. coli most intracellular spermidine is bound to nucleic acids and phospholipids. (EcoCyc)

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.

Sphingolipids have important structural and functional roles. They can be associated with membrane cholesterol and assist in forming specialized membrane domains. Sphingolipids, similar to phospholipids, have a polar head group with two nonpolar tails. Sphingolipids differ from phospholipids by their sphingosine core, a long-chain amino alcohol. sphingomyelins and glycosphingolipids are sphingolipids. Sphingolipids are produced in the endoplasmic reticulum. Sphinoglipid synthesis begins with palmitoyl-CoA and serine producing 3-keto-dihydrosphingosine by serine palmitoyltransferase. 3-Keto-dihydrosphingosine is then reduced to dihydrosphingosine which is then acylated to form dihydroceramide. Dihydroceramide is then dehyrogenated to ceramide. Ceramides are a sphingosine and fatty acid connected by an amide bond and can be produced by metabolism of sphingolipids. Ceramide can also be broken down back to sphingosine. Ceramide gets transported to the Golgi where it forms sphingomyelin or glycosphingolipids. From the Golgi, these products are transported by vesicles to specialized membrane domains.

catabolism and anabolism of sphingomyelin