Browsing Pathways

The biosynthesis of shikimate starts with D-Erythrose-4-phosphate getting transformed into 3-deoxy-D-arabino-heptulosonate-7-phosphate through a phospho-2-dehydro-3-deoxyheptonate aldolase. This is followed by a 3-dehydroquinate synthase converting the 3-deoxy-D-arabino-heptulosonate-7-phosphate into a 3-dehydroquinate which in turn is conveted to 3-dehydroshikimate through a 3-dehydroquinate dehydratase. A this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving an NADPH driven Quinate/shikimate dehydrogenase or a NADPH driven shikimate dehydrogenase 2. Shikimate can also be transported through a shikimate:H+ symporter.

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 biosynthesis of shikimate starts with D-Erythrose-4-phosphate getting transformed into 3-deoxy-D-arabino-heptulosonate-7-phosphate through a phospho-2-dehydro-3-deoxyheptonate aldolase. This is followed by a 3-dehydroquinate synthase converting the 3-deoxy-D-arabino-heptulosonate-7-phosphate into a 3-dehydroquinate which in turn is conveted to 3-dehydroshikimate through a 3-dehydroquinate dehydratase. A this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving an NADPH driven Quinate/shikimate dehydrogenase or a NADPH driven shikimate dehydrogenase 2. Shikimate can also be transported through a shikimate:H+ symporter.

The biosynthesis of Valine and L-leucine from pyruvic acid starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase resulting in a release of a carbon dioxide, a (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through a NADPH-driven acetohydroxy acid isomeroreductase resulting in the release of a NADP, a (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of a water molecule an 3-methyl-2-oxovaleric acid. The 3-methyl-2-oxovaleric acid can produce an L-valine by interacting with a L-glutamic acid through a Valine Transaminase resulting in the release of a Oxoglutaric acid and a L-valine. The 3-methyl-2-oxovaleric acid then interacts with an acetyl-CoA and a water molecule through a 2-isopropylmalate synthase resulting in the release of a hydrogen ion, a Coenzyme A and a 2-Isopropylmalic acid. The isopropylimalic acid is then hydrated by interacting with a isopropylmalate isomerase resulting in a 3-isopropylmalate. This compound then interacts with an NAD driven 3-isopropylmalate dehydrogenase resulting in a NADH, a hydrogen ion and a 2-isopropyl-3-oxosuccinate. The latter compound then interacts with hydrogen ion spontaneously resulting in a carbon dioxide and a ketoleucine. The ketoleucine then interacts with a L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in the oxoglutaric acid and L-leucine.

The biosynthesis of ubiquinol starts the interaction of 4-hydroxybenzoic acid interacting with an octaprenyl diphosphate. The former compound comes from the chorismate interacting with a chorismate lyase resulting in the release of a pyruvic acid and a 4-hydroxybenzoic acid. On the other hand, the latter compound, octaprenyl diphosphate is the result of a farnesyl pyrophosphate interacting with an isopentenyl pyrophosphate through an octaprenyl diphosphate synthase resulting in the release of a pyrophosphate and an octaprenyl diphosphate. The 4-hydroxybenzoic acid interacts with octaprenyl diphosphate through a 4-hydroxybenzoate octaprenyltransferase resulting in the release of a pyrophosphate and a 3-octaprenyl-4-hydroxybenzoate. The latter compound then interacts with a hydrogen ion through a 3-octaprenyl-4-hydroxybenzoate carboxy-lyase resulting in the release of a carbon dioxide and a 2-octaprenylphenol. The latter compound interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenylphenol hydroxylase resulting in a NADP, a water molecule and a 2-octaprenyl-6-hydroxyphenol. The 2-octaprenyl-6-hydroxyphenol interacts with an S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in the release of a hydrogen ion, an s-adenosylhomocysteine and a 2-methoxy-6-(all-trans-octaprenyl)phenol. The latter compound then interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenyl-6-methoxyphenol hydroxylase resulting in a NADP, a water molecule and a 2-methoxy-6-all trans-octaprenyl-2-methoxy-1,4-benzoquinol. The latter compound interacts with a S-adenosylmethionine through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a s-adenosylhomocysteine, a hydrogen ion and a 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. The 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. interacts with a reduced acceptor, an oxygen molecule through a 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase resulting in the release of a water molecule, an oxidized electron acceptor and a 3-demethylubiquinol-8. The latter compound then interacts with a S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in a hydrogen ion, a S-adenosylhomocysteine and a ubiquinol 8.

Cobinamide is incorporated from the extracellular space through a transport system into the cytosol. Once inside the cytosol, cobinamide interacts with ATP through a cobinamide adenosyl transferase resulting in the release of a triphosphate and an adenosylcobinamide. The latter compound is then phosphorylated through an ATP-dependent cobinamide kinase resulting in the release of ADP, a hydrogen ion and adenosyl-cobinamide phosphate. This last compound then interacts with GTP and a hydrogen ion through a cobinamide-P guanylyltransferase resulting in the release of a pyrophosphate and an adenosylcobinamide-GDP. A dimethylbenzimidazole interacts with a nicotinate D-ribonucleotide through a nicotinate-nucleotide dimethylbenzumidazole phosphoribosyltransferase resulting in the release of a nicotinate, a hydrogen ion and an alpha-ribazole 5' phosphate. The adenosylcobinamide-GDP and the alpha-ribazole 5' phosphate interact together through a cobalamin 5' phosphate synthase resulting in the release of a hydrogen ion, a GMP and Adenosylcobalamin 5'-phosphate. The latter compound then interacts with a water molecule through an adenosylcbalamin 5' phosphate phosphatase resulting in the release of a phosphate and a coenzyme B12. Likewise a cobalamin molecule can interact with ATP through a cobalamin adenosyltransferase resulting in the release of a triphosphate and a coenzyme B12

Cobinamide is incorporated from the extracellular space through a transport system into the cytosol. Once inside the cytosol, cobinamide interacts with ATP through a cobinamide adenosyl transferase resulting in the release of a triphosphate and an adenosylcobinamide. The latter compound is then phosphorylated through an ATP-dependent cobinamide kinase resulting in the release of ADP, a hydrogen ion and adenosyl-cobinamide phosphate. This last compound then interacts with GTP and a hydrogen ion through a cobinamide-P guanylyltransferase resulting in the release of a pyrophosphate and an adenosylcobinamide-GDP. A dimethylbenzimidazole interacts with a nicotinate D-ribonucleotide through a nicotinate-nucleotide dimethylbenzumidazole phosphoribosyltransferase resulting in the release of a nicotinate, a hydrogen ion and an alpha-ribazole 5' phosphate. The adenosylcobinamide-GDP and the alpha-ribazole 5' phosphate interact together through a cobalamin 5' phosphate synthase resulting in the release of a hydrogen ion, a GMP and Adenosylcobalamin 5'-phosphate. The latter compound then interacts with a water molecule through an adenosylcbalamin 5' phosphate phosphatase resulting in the release of a phosphate and a coenzyme B12. Likewise a cobalamin molecule can interact with ATP through a cobalamin adenosyltransferase resulting in the release of a triphosphate and a coenzyme B12

The biosynthesis of ubiquinol starts the interaction of 4-hydroxybenzoic acid interacting with an octaprenyl diphosphate. The former compound comes from the chorismate interacting with a chorismate lyase resulting in the release of a pyruvic acid and a 4-hydroxybenzoic acid. On the other hand, the latter compound, octaprenyl diphosphate is the result of a farnesyl pyrophosphate interacting with an isopentenyl pyrophosphate through an octaprenyl diphosphate synthase resulting in the release of a pyrophosphate and an octaprenyl diphosphate. The 4-hydroxybenzoic acid interacts with octaprenyl diphosphate through a 4-hydroxybenzoate octaprenyltransferase resulting in the release of a pyrophosphate and a 3-octaprenyl-4-hydroxybenzoate. The latter compound then interacts with a hydrogen ion through a 3-octaprenyl-4-hydroxybenzoate carboxy-lyase resulting in the release of a carbon dioxide and a 2-octaprenylphenol. The latter compound interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenylphenol hydroxylase resulting in a NADP, a water molecule and a 2-octaprenyl-6-hydroxyphenol. The 2-octaprenyl-6-hydroxyphenol interacts with an S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in the release of a hydrogen ion, an s-adenosylhomocysteine and a 2-methoxy-6-(all-trans-octaprenyl)phenol. The latter compound then interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenyl-6-methoxyphenol hydroxylase resulting in a NADP, a water molecule and a 2-methoxy-6-all trans-octaprenyl-2-methoxy-1,4-benzoquinol. The latter compound interacts with a S-adenosylmethionine through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a s-adenosylhomocysteine, a hydrogen ion and a 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. The 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. interacts with a reduced acceptor, an oxygen molecule through a 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase resulting in the release of a water molecule, an oxidized electron acceptor and a 3-demethylubiquinol-8. The latter compound then interacts with a S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in a hydrogen ion, a S-adenosylhomocysteine and a ubiquinol 8.

Cobinamide is incorporated from the extracellular space through a transport system into the cytosol. Once inside the cytosol, cobinamide interacts with ATP through a cobinamide adenosyl transferase resulting in the release of a triphosphate and an adenosylcobinamide. The latter compound is then phosphorylated through an ATP-dependent cobinamide kinase resulting in the release of ADP, a hydrogen ion and adenosyl-cobinamide phosphate. This last compound then interacts with GTP and a hydrogen ion through a cobinamide-P guanylyltransferase resulting in the release of a pyrophosphate and an adenosylcobinamide-GDP. A dimethylbenzimidazole interacts with a nicotinate D-ribonucleotide through a nicotinate-nucleotide dimethylbenzumidazole phosphoribosyltransferase resulting in the release of a nicotinate, a hydrogen ion and an alpha-ribazole 5' phosphate. The adenosylcobinamide-GDP and the alpha-ribazole 5' phosphate interact together through a cobalamin 5' phosphate synthase resulting in the release of a hydrogen ion, a GMP and Adenosylcobalamin 5'-phosphate. The latter compound then interacts with a water molecule through an adenosylcbalamin 5' phosphate phosphatase resulting in the release of a phosphate and a coenzyme B12. Likewise a cobalamin molecule can interact with ATP through a cobalamin adenosyltransferase resulting in the release of a triphosphate and a coenzyme B12

The biosynthesis of ubiquinol starts the interaction of 4-hydroxybenzoic acid interacting with an octaprenyl diphosphate. The former compound comes from the chorismate interacting with a chorismate lyase resulting in the release of a pyruvic acid and a 4-hydroxybenzoic acid. On the other hand, the latter compound, octaprenyl diphosphate is the result of a farnesyl pyrophosphate interacting with an isopentenyl pyrophosphate through an octaprenyl diphosphate synthase resulting in the release of a pyrophosphate and an octaprenyl diphosphate. The 4-hydroxybenzoic acid interacts with octaprenyl diphosphate through a 4-hydroxybenzoate octaprenyltransferase resulting in the release of a pyrophosphate and a 3-octaprenyl-4-hydroxybenzoate. The latter compound then interacts with a hydrogen ion through a 3-octaprenyl-4-hydroxybenzoate carboxy-lyase resulting in the release of a carbon dioxide and a 2-octaprenylphenol. The latter compound interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenylphenol hydroxylase resulting in a NADP, a water molecule and a 2-octaprenyl-6-hydroxyphenol. The 2-octaprenyl-6-hydroxyphenol interacts with an S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in the release of a hydrogen ion, an s-adenosylhomocysteine and a 2-methoxy-6-(all-trans-octaprenyl)phenol. The latter compound then interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenyl-6-methoxyphenol hydroxylase resulting in a NADP, a water molecule and a 2-methoxy-6-all trans-octaprenyl-2-methoxy-1,4-benzoquinol. The latter compound interacts with a S-adenosylmethionine through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a s-adenosylhomocysteine, a hydrogen ion and a 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. The 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. interacts with a reduced acceptor, an oxygen molecule through a 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase resulting in the release of a water molecule, an oxidized electron acceptor and a 3-demethylubiquinol-8. The latter compound then interacts with a S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in a hydrogen ion, a S-adenosylhomocysteine and a ubiquinol 8.