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.

Spermidine metabolism starts with S-adenosyl-L-methionine reacting with a hydrogen ion through a adenosylmethionine decarboxylase resulting in the release of a carbon dioxide and a S-adenosyl 3-(methylthio)propylamine. The later compound in turn reacts with putrescine resulting in the release of a hydrogen ion, a spermidine and a S-methyl-5'-thioadenosine. S-methyl-5'-thioadenosine in turn reacts with a water molecule through a 5-methylthioadenosine nucleosidase resulting in the release of a adenine and a S-methyl-5-thio-D-ribose which in in turn is released into the environment.

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 S-adenosyl-L-methionine cycle starts with S-adenosyl-L-methionine reacting with (a demethylated methyl donor ) dimethylglycine resulting in the release of a hydrogen ion, a betain (a methylated methyl donor) and a S-adenosyl-L-homocysteine. The s-adenosyl-L-homocysteine reacts with a water molecule through a S-adenosylhomocysteine nucleosidase resulting in the release of a adenine and a ribosyl-L-homocysteine. This compound in turn reacts with a s-ribosylhomocysteine lyase resulting in the release of a l-homocysteine and a autoinducer 2. The L-homocysteine reacts with a N5-methyl-tetrahydropteroyl tri-L-glutamate through a methionine synthase resulting in the release of a tetrahydropteroyl tri-L-glutamate and a methione. The methionine in turn reacts with a water molecule and ATP molecule through a methionine adenosyltransferase resulting in the release of a diphosphate, a phosphate and a s-adenosyl-L-methionine.

Glycolysis is a metabolic pathway consisting of ten reactions that convert glucose to pyruvate, releasing energy to form ATP and NADH. It occurs in two phases: the chemical priming phase and the energy-yielding phase. In the priming phase, D-glucose, which can be imported or derived from galactose metabolism, is phosphorylated to glucose-6-phosphate by a hexokinase-like enzyme, using ATP. This is then converted to fructose-6-phosphate, which is further phosphorylated to fructose-1,6-bisphosphate by 6-phosphofructokinase, also using ATP. Aldolase then splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which can interconvert via triosephosphate isomerase. In the energy-yielding phase, glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase, producing NADH in the process. ATP is generated when 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate. Further steps involve the conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase, followed by conversion to phosphoenolpyruvate by enolase. Finally, pyruvate kinase converts phosphoenolpyruvate to pyruvate, producing ATP in the process. Pyruvate then participates in further metabolic pathways, including pyruvate metabolism, tyrosine metabolism, and the synthesis of pantothenate and CoA.

Glycolysis is a metabolic pathway consisting of ten reactions that convert glucose to pyruvate, releasing energy to form ATP and NADH. It occurs in two phases: the chemical priming phase and the energy-yielding phase. In the priming phase, D-glucose, which can be imported or derived from galactose metabolism, is phosphorylated to glucose-6-phosphate by a hexokinase-like enzyme, using ATP. This is then converted to fructose-6-phosphate, which is further phosphorylated to fructose-1,6-bisphosphate by 6-phosphofructokinase, also using ATP. Aldolase then splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which can interconvert via triosephosphate isomerase. In the energy-yielding phase, glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase, producing NADH in the process. ATP is generated when 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate. Further steps involve the conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase, followed by conversion to phosphoenolpyruvate by enolase. Finally, pyruvate kinase converts phosphoenolpyruvate to pyruvate, producing ATP in the process. Pyruvate then participates in further metabolic pathways, including pyruvate metabolism, tyrosine metabolism, and the synthesis of pantothenate and CoA.

Fructosamines are compounds that result from glycation reactions between a sugar and a primary amine, followed by isomerization via the Amadori rearrangement. In fructoselysine degradation, fructoselysine firstly converts to 1-[(5-Amino-5-carboxypentyl)amino]-1-deoxyfructose by protein frlC, and then 1-[(5-Amino-5-carboxypentyl)amino]-1-deoxyfructose is transformed to fructoselysine-6-phosphate by fructoselysine kinase which is powered by ATP. Fructoselysine-6-phosphate finally degrades to β-D-Glucose 6-phosphate and L-lysine by fructoselysine 6-phosphate deglycase.

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.

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.