Browsing Pathways

The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. Glutathione can then be degraded into various different glutathione containing compounds by reacting with a napthalene or Bromobenzene-2,3-oxide through a glutathione S-transferase.

The synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate. N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound can either be isomerized or deaminated into Beta-D-fructofuranose 6-phosphate through a glucosamine-fructose-6-phosphate aminotransferase and a glucosamine-6-phosphate deaminase respectively. Glucosamine 6-phosphate undergoes a reversible reaction to glucosamine 1 phosphate through a phosphoglucosamine mutase. This compound is then acetylated through a bifunctional protein glmU to produce a N-Acetyl glucosamine 1-phosphate. N-Acetyl glucosamine 1-phosphate enters the nucleotide sugar synthesis by reacting with UTP and hydrogen ion through a bifunctional protein glmU releasing pyrophosphate and a Uridine diphosphate-N-acetylglucosamine.This compound can either be isomerized into a UDP-N-acetyl-D-mannosamine or undergo a reaction with phosphoenolpyruvic acid through UDP-N-acetylglucosamine 1-carboxyvinyltransferase releasing a phosphate and a UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate. UDP-N-acetyl-D-mannosamine undergoes a NAD dependent dehydrogenation through a UDP-N-acetyl-D-mannosamine dehydrogenase, releasing NADH, a hydrogen ion and a UDP-N-Acetyl-alpha-D-mannosaminuronate, This compound is then used in the production of enterobacterial common antigens. UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate is reduced through a NADPH dependent UDP-N-acetylenolpyruvoylglucosamine reductase, releasing a NADP and a UDP-N-acetyl-alpha-D-muramate. The latter is also involved in the D-glutamine and D-glutamate metabolism.

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 phosphoribosyl pyrophosphate begins as a product of the pentose phosphate and D-ribose 5-phosphate interaction. When catalyzed with a phosphopentomutase, the product is a ribose 1-phosphate. Ribose 1-phosphate can interact spontaneously with ATP resulting in a release of hydrogen ion, ADP and a ribose 1,5-biphosphate. Ribose 1,5-biphosphate is then phosphorylated through a ribose 1,5-bisphosphokinase resulting in the release of ADP and phosphoribosyl pyrophosphate. Phosphoribosyl pyrophosphate will then participate in the purine nucleotides de novo biosynthesis pathway. Alternatively pentose phosphate and D-ribose 5-phosphate's interaction can be phosphorylated through an ATP driven ribose-phosphate diphosphokinase resulting in a release of a hydrogen ion, an AMP and a phosphoribosyl pyrophosphate which will again participate in the purine nucleotides de novo biosynthesis pathway.

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.

The degradation of galactose, also known as Leloir pathway, requires 3 main enzymes once Beta-D-galactose has been converted to galactose through an Aldose-1-epimerase. These are: galactokinase , galactose-1-phosphate uridylyltransferase and UDP-glucose 4-epimerase. Beta-D-galactose can be uptaken from the environment through a galactose proton symporter. It can also be produced by lactose degradation involving a lactose permease to uptake lactose from the environment and a beta-galactosidase to turn lactose into Beta-D-galactose. Galactose is degraded through the following process: Beta-D-galactose is introduced into the cytoplasm through a galactose proton symporter, or it can be synthesized from an alpha lactose that is introduced into the cytoplasm through a lactose permease. Alpha lactose interacts with water through a beta-galactosidase resulting in a beta-D-glucose and beta-D-galactose. Beta-D-galactose is isomerized into D-galactose. D-Galactose undergoes phosphorylation through a galactokinase, hence producing galactose 1 phosphate. On the other side of the pathway, a gluose-1-phosphate (product of the interaction of alpha-D-glucose 6-phosphate with a phosphoglucomutase resulting in a alpha-D-glucose-1-phosphate, an isomer of Glucose 1-phosphate, or an isomer of Beta-D-glucose 1-phosphate) interacts with UTP and a hydrogen ion in order to produce a uridine diphosphate glucose. This is followed by the interaction of galactose-1-phosphate with an established amount of uridine diphosphate glucose through a galactose-1-phosphate uridylyltransferase, which in turn output a glucose-1-phosphate and a uridine diphosphate galactose. The glucose -1-phosphate is transformed into a uridine diphosphate glucose through UTP--glucose-1-phosphate uridylyltransferase. The product, uridine diphosphate glucose, can undergo a reversible reaction in which it can be turned into uridine diphosphategalactose through an UDP-glucose 4-epimerase, and so the cycle can keep going as long as more lactose or galactose is imported into the cell.

Beta-D-glucuronosides, D-glucuronate and D-fructuronate can be used as a source of carbon for E.coli. They are imported into E.coli's periplasmic space by membrane-associated protein (UidC/gusC), and are further imported into cytoplasm by hydrogen symporter. Beta-glucuronides undergoes hydrolysis by beta-D-glucuronidase to form D-glucuronate. D-glucuronate is isomerized by D-glucuronate isomerase to form D-fructuronate. D-fructuronate is further reduced to D-mannonate by D-mannonate oxidoreductase. D-mannonate dehydratase dehydrated to yield 2-dehydro-3-deoxy-D-gluconate. At this point, a common enzyme, 2-keto-3-deoxygluconokinase, phosphorylates 2-dehydro-3-deoxy-D-gluconate to yield 2-dehydro-3-deoxy-D-gluconate-6-phosphate. This product is then process by KHG/KDPG aldolase which in turn produces D-Glyceraldehyde 3-phosphate and Pyruvic Acid which then go into their respective sub pathways: glycolysis and pyruvate dehydrogenase. The pathway can also start from 3 other points: a hydrogen ion symporter (gluconate/fructuronate transporter GntP) of D-fructuronate, a hydrogen ion symporter (Hexuronate transporter) of aldehydo-D-galacturonate that spontaneously turns into D-tagaturonate. This compound can also be obtained by the reaction of aldehydo-L-galactonate with a NAD dependent l-galactonate oxidoreductase resulting in the release of NADH, hydrogen ion. Tagaturonate then undergoes an NADH-dependent reduction to D-altronate through an altronate oxidoreductase. D-altronate undergoes dehydration to yield 2-dehydro-3-deoxy-D-gluconate, the third and last point where the reaction can start from a hydrogen symporter of a 2-dehydro-3-deoy-D-gluconate.

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 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.