Browsing Pathways

Lipopolysaccharide (LPS) is a major component of outer membrane which is consisted of lipid A-core (oligosaccharide) on both inner and outer region and O-antigen (known as distal repeating unit with four sugars: N-acetylglucosamine, glucose, rhamnose and galactose). O-antigen is part of three domains of LPS, which is attached to lipid A-core; however, O-antigen and lipid A-core are synthesized separately. In this pathway, synthesis of three of O-antigen sugars is demonstrated. UDP-α-D-galactose is converted to UDP-D-Galacto-1,4-furanose by facilitation of UDP-galactopyranose mutase. dTTP glucose-1-phosphate is derivatized to dTDP-rhamnose. Fructose-6-phosphate gains an amino group, incorporates an acetate moiety and then acquires a nucleoside diphosphate resulting in UDP-N-acetyl-D-glucosamine.

Rhamnolipids (RL) consist of a fatty acyl moiety composed of a 3-(3-hydroxyalkanoyloxy)alkaloid acid (HAA) and a sugar moiety composed of one or two rhamnose sugars. Rhamnolipids function as surfactants and virulence factors and are involved in biofilm formation and cell motility. The rhamnose sugar component is produced via the dTDP-L-rhamnose biosynthetic pathway which forms dTDP-L-rhamnose from glucose 6-phosphate (G6P) in five steps. First, glucose 6-phosphate is converted into glucose 1-phosphate (G1P) via the enzyme phosphoglucomutase (AlgC). Second, glucose 1-phosphate is converted into dTDP-D-glucose via the enzyme glucose-1-phosphate thymidylyltransferase (RmlA). Third, dTDP-D-glucose is converted into dTDP-4-dehydro-6-deoxy-D-glucose via the enzyme dTDP-glucose 4,6-dehydratase (RmlB). Fourth, dTDP-4-dehydro-6-deoxy-D-glucose is converted into dTDP-4-dehydro-L-rhamnose via the enzyme dTDP-4-dehydrorhamnose 3,5-epimerase (RmlC). Fifth, dTDP-4-dehydro-L-rhamnose is converted into dTDP-L-rhamnose via the enzyme dTDP-4-dehydrorhamnose reductase (RmlD). The HAA component is synthesized from 3-hydroxyacyl-[acyl-carrier protein] diverted from fatty acid biosynthesis via the enzyme 3-(3-hydroxydecanoyloxy)decanoate synthase (RhIA). The final step in rhamnolipid biosynthesis is the formation of the glycosidic link between the rhamnose sugar component and the HAA component. This is accomplished by two rhamnosyltransferases (RhlB and RhlC) which catalyze sequential glycosyl transfer reactions to first form mono-rhamnolipids (via RhIB) and then di-rhamnolipids (via RhIC). RHlA, RHlB, and RHlC are associated with the inner membrane.

L-threonine is degrade into methylglyoxal (pyruvaldehyde) by first reacting with a NDA dependent threonine dehydrogenase resulting in the release of a hydrogen ion, an NADH and a 2-amino-3-oxobutanoate. The latter compound reacts spontaneously with a hydrogen ion resulting in the release of a carbon dioxide and a aminoacetone. The aminoacetone in turn reacts with an oxygen and a water molecule through an aminoacetone oxidase resulting in the release of a hydrogen peroxide, ammonium and a methylglyoxal which can then be incorporated in the methylglyoxal degradation 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.

The citrate lyase activation starts with a 3-dephospho-CoA reacting with ATP and a hydrogen ion through a triphosphoribosyl-dephospho-CoA synthase resulting in a adenine and a 2'-(5'-triphospho-alpha-D-ribosyl)-3'-dephospho-CoA. The latter compound in turn reacts with with a citrate lyase acyl-carrier protein through a apo-citrate lyase phosphoribosyl-dephospho-CoA transferase resulting in the release of a pyrophosphate and a hydrogen ion and a holo citrate lyase acyl-carrier protein.This protein complex can either react with a hydrogen ion and a acetate resulting in the release of a water and an acetyl-holo citrate lyase acyl-carrier protein. The holo acyl-carrier protein creacts with an ATP and an acetate through a citrate lyase synthase resulting in the release of an AMP, a pyrophosphate and an acetyl-holo citrate lyase acyl-ccarrier protein. The holo citrate lyase acyl-carrier protein can also interact with an S-acetyl phosphopantethiene resulting in the release of a 4-phosphopantethiene and an acetyl-holo citrate lyase acyl-carrier protein.

ADP-L-glycero-β-D-manno-heptose is a precursor for the inner core lipopolysaccharide (LPS), which is the outer membrane of Gram-negative bacteria. LPS is consisted of lipid A, a core oligosaccharide, and an O-specific polysaccharide (O antigen). This biosynthesis pathway starts with catalyzation of D-sedoheptulose 7-phosphate that produced from pentose phosphate pathway to form D-glycero-D-manno-heptose 7-phosphate by lysophospholipid acyltransferase. D-glycero-D-manno-heptose 7-phosphate later undergoes catalyze to form D-glycero-β-D-manno-heptose 1,7-bisphosphate by fused heptose 7-phosphate kinase (also known as heptose 1-phosphate adenyltransferase) that powered by ATP. D-glycero-β-D-manno-heptose 1,7-bisphosphate will go through hydrolysis by D,D-heptose 1,7-bisphosphate phosphatase to form D-glycero-β-D-manno-heptose 1-phosphate and a phosphate. D-glycero-β-D-manno-heptose 1-phosphate will form ADP-D-Glycero-D-manno-heptose and diphosphate, and eventually ADP-D-Glycero-D-manno-heptose will be biotransformed to ADP-L-glycero-β-D-manno-heptose as the end product of this pathway by ADP-L-glycero-D-mannoheptose-6-epimerase.

Lipopolysaccharide (LPS) is a major component of outer membrane which is consisted of lipid A-core (oligosaccharide) on both inner and outer region and O-antigen (known as distal repeating unit with four sugars: N-acetylglucosamine, glucose, rhamnose and galactose). O-antigen is part of three domains of LPS, which is attached to lipid A-core; however, O-antigen and lipid A-core are synthesized separately. In this pathway, synthesis of three of O-antigen sugars is demonstrated. UDP-α-D-galactose is converted to UDP-D-Galacto-1,4-furanose by facilitation of UDP-galactopyranose mutase. dTTP glucose-1-phosphate is derivatized to dTDP-rhamnose. Fructose-6-phosphate gains an amino group, incorporates an acetate moiety and then acquires a nucleoside diphosphate resulting in UDP-N-acetyl-D-glucosamine.

Rhamnolipids (RL) consist of a fatty acyl moiety composed of a 3-(3-hydroxyalkanoyloxy)alkaloid acid (HAA) and a sugar moiety composed of one or two rhamnose sugars. Rhamnolipids function as surfactants and virulence factors and are involved in biofilm formation and cell motility. The rhamnose sugar component is produced via the dTDP-L-rhamnose biosynthetic pathway which forms dTDP-L-rhamnose from glucose 6-phosphate (G6P) in five steps. First, glucose 6-phosphate is converted into glucose 1-phosphate (G1P) via the enzyme phosphoglucomutase (AlgC). Second, glucose 1-phosphate is converted into dTDP-D-glucose via the enzyme glucose-1-phosphate thymidylyltransferase (RmlA). Third, dTDP-D-glucose is converted into dTDP-4-dehydro-6-deoxy-D-glucose via the enzyme dTDP-glucose 4,6-dehydratase (RmlB). Fourth, dTDP-4-dehydro-6-deoxy-D-glucose is converted into dTDP-4-dehydro-L-rhamnose via the enzyme dTDP-4-dehydrorhamnose 3,5-epimerase (RmlC). Fifth, dTDP-4-dehydro-L-rhamnose is converted into dTDP-L-rhamnose via the enzyme dTDP-4-dehydrorhamnose reductase (RmlD). The HAA component is synthesized from 3-hydroxyacyl-[acyl-carrier protein] diverted from fatty acid biosynthesis via the enzyme 3-(3-hydroxydecanoyloxy)decanoate synthase (RhIA). The final step in rhamnolipid biosynthesis is the formation of the glycosidic link between the rhamnose sugar component and the HAA component. This is accomplished by two rhamnosyltransferases (RhlB and RhlC) which catalyze sequential glycosyl transfer reactions to first form mono-rhamnolipids (via RhIB) and then di-rhamnolipids (via RhIC). RHlA, RHlB, and RHlC are associated with the inner membrane.

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.