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.

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.

Glycerol metabolism starts with glycerol is introduced into the cytoplasm through a glycerol channel GlpF Glycerol is then phosphorylated through an ATP mediated glycerol kinase resulting in a Glycerol 3-phosphate. This compound can also be obtained through a glycerophosphodiester reacting with water through a glycerophosphoryl diester phosphodiesterase or it can also be introduced into the cytoplasm through a glycerol-3-phosphate:phosphate antiporter. Glycerol 3-phosphate is then metabolized into a dihydroxyacetone phosphate in both aerobic or anaerobic conditions. In anaerobic conditions the metabolism is done through the reaction of glycerol 3-phosphate with a menaquinone mediated by a glycerol-3-phosphate dehydrogenase protein complex. In aerobic conditions, the metabolism is done through the reaction of glycerol 3-phosphate with ubiquinone mediated by a glycerol-3-phosphate dehydrogenase [NAD(P]+]. Dihydroxyacetone phosphate is then introduced into the fructose metabolism by turning a dihydroxyacetone into an isomer through a triosephosphate isomerase resulting in a D-glyceraldehyde 3-phosphate which in turn reacts with a phosphate through a NAD dependent Glyceraldehyde 3-phosphate dehydrogenase resulting in a glyceric acid 1,3-biphosphate. This compound is desphosphorylated by a phosphoglycerate kinase resulting in a 3-phosphoglyceric acid.This compound in turn can either react with a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase or a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase resulting in a 2-phospho-D-glyceric acid. This compound interacts with an enolase resulting in a phosphoenolpyruvic acid and water. Phosphoenolpyruvic acid can react either through a AMP driven phosphoenoylpyruvate synthase or a ADP driven pyruvate kinase protein complex resulting in a pyruvic acid. Pyruvic acid reacts with CoA through a NAD driven pyruvate dehydrogenase complex resulting in a carbon dioxide and a Acetyl-CoA which gets incorporated into the TCA cycle pathway.

The process of oxidative phosphorylation involves multiple interactions of ubiquinone with succinic acid, resulting in a fumaric acid and ubiquinol. Ubiquinone interacts with succinic acid through a succinate:quinone oxidoreductase resulting in a fumaric acid an ubiquinol. This enzyme has various cofactors, ferroheme b, 2FE-2S, FAD, and 3Fe-4S iron-sulfur cluster. Then 2 ubiquinol interact with oxygen and 4 hydrogen ion through a cytochrome bd-I terminal oxidase resulting in a 4 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stay in the inner membrane. The ubiquinone interacts with succinic acid through a succinate:quinone oxidoreductase resulting in a fumaric acid an ubiquinol. Then 2 ubiquinol interacts with oxygen and 4 hydrogen ion through a cytochrome bd-II terminal oxidase resulting in a 4 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stay in the inner membrane. The ubiquinone interacts with succinic acid through a succinate:quinone oxidoreductase resulting in a fumaric acid an ubiquinol. The 2 ubiquinol interact with oxygen and 8 hydrogen ion through a cytochrome bo terminal oxidase resulting in a 8 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stays in the inner membrane. The ubiquinone then interacts with 5 hydrogen ion through a NADH dependent ubiquinone oxidoreductase I resulting in NAD, hydrogen ion released into the periplasmic space and an ubiquinol. The ubiquinol is then processed reacting with oxygen, and 4 hydrogen through a ion cytochrome bd-I terminal oxidase resulting in 4 hydrogen ions released into the periplasmic space, 2 water molecules into the cytoplasm and 2 ubiquinones. The ubiquinone then interacts with 5 hydrogen ion through a NADH dependent ubiquinone oxidoreductase I resulting in NAD, hydrogen ion released into the periplasmic space and an ubiquinol. The 2 ubiquinol interact with oxygen and 8 hydrogen ion through a cytochrome bo terminal oxidase resulting in a 8 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stays in the inner membrane.

The process of oxidative phosphorylation involves multiple interactions of ubiquinone with succinic acid, resulting in a fumaric acid and ubiquinol. Ubiquinone interacts with succinic acid through a succinate:quinone oxidoreductase resulting in a fumaric acid an ubiquinol. This enzyme has various cofactors, ferroheme b, 2FE-2S, FAD, and 3Fe-4S iron-sulfur cluster. Then 2 ubiquinol interact with oxygen and 4 hydrogen ion through a cytochrome bd-I terminal oxidase resulting in a 4 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stay in the inner membrane. The ubiquinone interacts with succinic acid through a succinate:quinone oxidoreductase resulting in a fumaric acid an ubiquinol. Then 2 ubiquinol interacts with oxygen and 4 hydrogen ion through a cytochrome bd-II terminal oxidase resulting in a 4 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stay in the inner membrane. The ubiquinone interacts with succinic acid through a succinate:quinone oxidoreductase resulting in a fumaric acid an ubiquinol. The 2 ubiquinol interact with oxygen and 8 hydrogen ion through a cytochrome bo terminal oxidase resulting in a 8 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stays in the inner membrane. The ubiquinone then interacts with 5 hydrogen ion through a NADH dependent ubiquinone oxidoreductase I resulting in NAD, hydrogen ion released into the periplasmic space and an ubiquinol. The ubiquinol is then processed reacting with oxygen, and 4 hydrogen through a ion cytochrome bd-I terminal oxidase resulting in 4 hydrogen ions released into the periplasmic space, 2 water molecules into the cytoplasm and 2 ubiquinones. The ubiquinone then interacts with 5 hydrogen ion through a NADH dependent ubiquinone oxidoreductase I resulting in NAD, hydrogen ion released into the periplasmic space and an ubiquinol. The 2 ubiquinol interact with oxygen and 8 hydrogen ion through a cytochrome bo terminal oxidase resulting in a 8 hydrogen ion transferred into the periplasmic space, 2 water returned into the cytoplasm and 2 ubiquinone, which stays in 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.

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.