Browsing Pathways

Pseudouridine is phosphorylated by interacting with atp and a psuK resulting in the release of an ADP, a hydrogen ion and a pseudouridine 5'-phosphate. The latter compound then reacts with water through a pseudouridine 5'-phosphate glycosidase resulting in the release of a uracil and D-ribofuranose 5-phosphate

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.

Phospholipids are membrane components in E. coli. The major phospholipids of E. coli are phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions. The reaction starts from a glycerone phosphate (dihydroxyacetone phosphate) produced in glycolysis. The glycerone phosphate is transformed into an sn-glycerol 3-phosphate (glycerol 3 phosphate) by NADPH-driven glycerol-3-phosphate dehydrogenase. sn-Glycerol 3-phosphate is transformed to a 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid). This can be achieved by an sn-glycerol-3-phosphate acyltransferase that interacts either with a long-chain acyl-CoA or with an acyl-[acp]. The 1-acyl-sn-glycerol 3-phosphate is transformed into a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) through a 1-acylglycerol-3-phosphate O-acyltransferase. This compound is then converted into a CPD-diacylglycerol through a CTP phosphatidate cytididyltransferase. CPD-diacylglycerol can be transformed either into an L-1-phosphatidylserine or an L-1-phosphatidylglycerol-phosphate through a phosphatidylserine synthase or a phosphatidylglycerophosphate synthase, respectively. The L-1-phosphatidylserine transforms into L-1-phosphatidylethanolamine through a phosphatidylserine decarboxylase. On the other hand, L-1-phosphatidylglycerol-phosphate gets transformed into an L-1-phosphatidyl-glycerol through a phosphatidylglycerophosphatase. These 2 products combine to produce a cardiolipin and an ethanolamine. The L-1 phosphatidyl-glycerol can also interact with cardiolipin synthase resulting in a glycerol and a cardiolipin.

The process of oleic acid B-oxidation starts with a 2-trans,5-cis-tetradecadienoyl-CoA that can be either be processed by an enoyl-CoA hydratase by interacting with a water molecules resulting in a 3-hydroxy-5-cis-tetradecenoyl-CoA, which can be oxidized in the fatty acid beta-oxidation. On the other hand 2-trans,5-cis-tetradecadienoyl-CoA can become a 3-trans,5-cis-tetradecadienoyl-CoA through a isomerase. This results interact with a water molecule through a acyl-CoA thioesterase resulting in a hydrogen ion, a coenzyme A and a 3,5-tetradecadienoate

Pseudouridine is phosphorylated by interacting with atp and a psuK resulting in the release of an ADP, a hydrogen ion and a pseudouridine 5'-phosphate. The latter compound then reacts with water through a pseudouridine 5'-phosphate glycosidase resulting in the release of a uracil and D-ribofuranose 5-phosphate

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.

GTP, produced in the nucleotide de novo biosyntheis pathway, interacts with a water molecule through a GTP cyclohydrolase resulting in a formate, hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound interacts with a water molecule through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, a hydrogen ion and a 7,8-dihydroneopterin 3'-phosphate. The latter compound interacts with water spontaneously resulting in the release of a phosphate and a 7,8 dihydroneopterin. The latter compound interacts with a dihydroneopterin aldolase resulting in the release of a glycolaldehyde and a 6-hydroxymethyl-7,8-dihydropterin. This compound then is then diphosphorylated by reacting with a ATP driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in the release of a hydrogen ion, an AMP and 6-hydroxymethyl-7,8-dihydropterin diphosphate. GTP interacts with a cyclic pyranopterin monophosphate synthase resulting in the release of a diphosphate and a cyclic pyranopterin phosphate. The latter compound interacts with a thiocarboxylated small subunit of molybdopterin synthase (a protein) and a water molecule through a molybdopterin synthase resulting in the release of 4 hydrogen ions, 2 small subunits of molybdopterin synthase and a molybdopterin. The molybdopterin interacts with an ATP and a hydrogen ion through a molybdopterin adenylyltransferase resulting in the release of a diphosphate and a molybdopterin adenine dinucleotide. The latter compound is then metabolized by a hydrogen ion and a molybdate through a molybdopterin molybdenumtransferase resulting in the release of an AMP, a water molecule and a molybdopterin cofactor. The molybdopterin cofactor can procede to the guanylyl molybdenum cofactor biosynthesis pathway or it can be metabolized into a cytidylyl molybdenum cofactor by interacting with a CTP and a hydrogen ion through a molybdenym cofactor cytidylyltransferase resulting in the release of a pyrophosphate and a cytidyllyl molybdenum cofactor

GTP, produced in the nucleotide de novo biosyntheis pathway, interacts with a water molecule through a GTP cyclohydrolase resulting in a formate, hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound interacts with a water molecule through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, a hydrogen ion and a 7,8-dihydroneopterin 3'-phosphate. The latter compound interacts with water spontaneously resulting in the release of a phosphate and a 7,8 dihydroneopterin. The latter compound interacts with a dihydroneopterin aldolase resulting in the release of a glycolaldehyde and a 6-hydroxymethyl-7,8-dihydropterin. This compound then is then diphosphorylated by reacting with a ATP driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in the release of a hydrogen ion, an AMP and 6-hydroxymethyl-7,8-dihydropterin diphosphate. GTP interacts with a cyclic pyranopterin monophosphate synthase resulting in the release of a diphosphate and a cyclic pyranopterin phosphate. The latter compound interacts with a thiocarboxylated small subunit of molybdopterin synthase (a protein) and a water molecule through a molybdopterin synthase resulting in the release of 4 hydrogen ions, 2 small subunits of molybdopterin synthase and a molybdopterin. The molybdopterin interacts with an ATP and a hydrogen ion through a molybdopterin adenylyltransferase resulting in the release of a diphosphate and a molybdopterin adenine dinucleotide. The latter compound is then metabolized by a hydrogen ion and a molybdate through a molybdopterin molybdenumtransferase resulting in the release of an AMP, a water molecule and a molybdopterin cofactor. The molybdopterin cofactor can procede to the guanylyl molybdenum cofactor biosynthesis pathway or it can be metabolized into a cytidylyl molybdenum cofactor by interacting with a CTP and a hydrogen ion through a molybdenym cofactor cytidylyltransferase resulting in the release of a pyrophosphate and a cytidyllyl molybdenum cofactor

The pathway can start in various spots. First step in this case starts with NADH interacting with a menaquinone oxidoreductase resulting in the release of a NADH and a hydrogen Ion, at the same time in the inner membrane a menaquinone interacts with 2 electrons and 2 hydrogen ions thus releasing a menaquinol. This allows for 4 hydrogen ions to be transferred from the cytosol to the periplasmic space. The menaquinol then interacts with a trimethylamine N-oxide reductase resulting in the release of 2 hydrogen ion and 2 electrons. At the same time trimethylamine N-oxide and 3 hydrogen ions interact with the enzyme trimethylamine N-oxide reductase resulting in the release of a trimethylamine and a water molecule, this reaction happening in the periplasmic space. The second set of reactions starts with a hydrogen interacting with a menaquinone oxidoreductase resulting in the release of two electrons being released into the inner membrane which then react with with 2 hydrogen ion and a menaquinone to produce a menaquinol. This menaquinol then reacts with a trimethylamine N-oxide reductase following the same steps as mentioned before. The third set of reactions starts with with formate interacting with a formate dehydrogenase-O resulting in a release of carbon dioxide and a hydrogen ion, this releases 2 electrons that interact with a menaquinone and two hydrogen ions. This releases a menaquinol which then reacts with a trimethylamine N-oxide reductase following the same steps as mentioned before