Browsing Pathways

The N-glycan biosynthesis is a pathway involving the creation of a dolichol, and the consecutive reactions involving the addition of Acetylglucosaminyl groups, mannosyl groups and glucosyl groups. The set of reactions all happen in the ER membrane. The resulting glucosyl3mannosyl9-N-acetylglucosaminyl2-diphosphodolichol is used as protein modificator.

The TCA cycle (tricarboxylic acid cycle) is also known as the citric acid cycle and the Krebs cycle. This pathway is the catabolism of aerobic respiration which produces energy and reducing power. It also initiates the production of precursors necessary for biosynthesis. If the carbon source for the cycle is acetate then citrate synthase becomes rate-limiting. Respiration produces ATP through a process of compounds acting as electron donors transferring electrons to electron acceptors. During this electron transport chain, a proton motive force is generated by the transport of protons outside the cytoplasmic membrane. As protons return to the cytoplasm, a multisubunit ATPase catalyzes the production of ATP from the proton motive force energy. During aerobic respiration, the final electron acceptor is oxygen. During anaerobic respiration, several organic compounds act as acceptors such as hydrogen, fumarate and nitrate. The cycle can start from Acetyl-CoA interacting with Oxalacetic acid and water through a citrate synthase monomer resulting in a hydrogen ion, CoA and a Citric Acid. The latter compound is dehydrated by a Citrate hydro-lyase resulting in the release of water and a cis-Aconitic acid. This compound is then hydrated through a Citrate hydro-lyase resulting in a D-threo-Isocitric acid. This compound is decarboxylated by an NADP dependent Citrate dehydrogenase, resulting in a release of carbon dioxide and NADPH and Oxoglutaric acid. The oxoglutaric acid interacts with a Coenzyme A through a NAD driven 2-oxoglutarate dehydrogenase resulting in a release of carbon dioxide, an NADH and succinyl-CoA. The succinyl-CoA interacts with a phosphate and an ADP through a 2-oxoglutarate dehydrogenase resulting in a CoA, an ATP and Succinic Acid. Succinic acid interacts with a ubiquinone, in this case a ubiquinone 1 through a succinate:quinone oxidoreductase resulting in an ubiquinol, in this case a ubiquinol-1 and a fumaric acid. The fumaric acid interacts with water through a fumarase hydratase resulting in a L-Malic acid. Malic acid can either react with a NAD dependent dehydrogenase resulting in the release of pyruvate. Malic Acid acid can also react with a malate dehydrogenase resulting in the release of oxalacetic acid

Sphingolipids have important structural and functional roles. They can be associated with membrane cholesterol and assist in forming specialized membrane domains. Sphingolipids, similar to phospholipids, have a polar head group with two nonpolar tails. Sphingolipids differ from phospholipids by their sphingosine core, a long-chain amino alcohol. sphingomyelins and glycosphingolipids are sphingolipids. Sphingolipids are produced in the endoplasmic reticulum. Sphinoglipid synthesis begins with palmitoyl-CoA and serine producing 3-keto-dihydrosphingosine by serine palmitoyltransferase. 3-Keto-dihydrosphingosine is then reduced to dihydrosphingosine which is then acylated to form dihydroceramide. Dihydroceramide is then dehyrogenated to ceramide. Ceramides are a sphingosine and fatty acid connected by an amide bond and can be produced by metabolism of sphingolipids. Ceramide can also be broken down back to sphingosine. Ceramide gets transported to the Golgi where it forms sphingomyelin or glycosphingolipids. From the Golgi, these products are transported by vesicles to specialized membrane domains.

Carbohydrates are a major component of the diet, and include starch (amylose and amylopectin) and disaccharides such as sucrose, lactose, maltose and, in small amounts, trehalose. Once released from starch or once ingested, sucrose can be degraded into beta-D-fructose and alpha-D-glucose via lysosomal alpha-glucosidase or sucrose-isomaltase. Beta-D-Fructose can be converted to beta-D-fructose-6-phosphate by glucokinase and then to alpha-D-glucose-6-phosphate by the action of glucose phosphate isomerase. Phosphoglucomutase 1 can then act on alpha-D-glucose-6-phosphate (G6P) to generate alpha-D-glucose-1-phosphate. alpha-D-Glucose-1-phosphate (G6P) has several possible fates. It can enter into gluconeogenesis, glycolysis, or the nucleotide sugar metabolism pathway. UDP-glucose pyrophosphorylase 2 can convert alpha-D-glucose-1-phosphate into UDP-glucose, UDP-glucose can then be used to produce D-glucose via trehalose. UDP-glucose can also serve as a precursor to the synthesis of glycogen via glycogen synthase. Glycogen is a starch analogue commonly called an animal starch. Glycogen is found in the cytosol in granules. Glycogen is cleaved and converted to glucose-6-phosphate (G6P) which undergoes glycolysis or can enter the pentose phosphate pathway.

The biosynthesis of thiamine begins with pyrithiamine reacting with thiaminase 2 resulting in the release of 4-Amino-5-hydroxymethyl-2-methylpyrimidine. The latter compound reacts with a hydroxymethylpyrimidine/phosphomethylpyrimidine kinase resulting in the release of 4-amino-2-methyl-5-phosphomethylpyrimidine. The latter compound reacts with a hydroxymethylpyrimidine/phosphomethylpyrimidine kinase resulting in the release of 2-Methyl-4-amino-5-hydroxymethylpyrimidine diphosphate. The latter compound reacts with 4-methyl-5-(2-phosphonooxyethyl)thiazole, a product of oxythiamine metabolism, through a Thiamine biosynthetic bifunctional enzyme resultin in the release of a Thiamine monophosphate. The latter compound is phosphatased through a acid phosphatase complex resulting in the release of thiamine. The latter compound is phosphorylated through a thiamin pyrophosphokinase resulting in the release of thiamine pyrophosphate.

The pathway of valine biosynthesis starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase or a acetohydroxybutanoate synthase / acetolactate synthase resulting in the release of carbon dioxide and (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through an NADPH driven acetohydroxy acid isomeroreductase resulting in the release of a NADP and an (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of water and isovaleric acid. Isovaleric acid interacts with an L-glutamic acid through a Valine Transaminase resulting in a oxoglutaric acid and an L-valine.

CMP-3-deoxy-D-manno-octulosonate (CMP-Kdo) biosynthesis is a pathway that occurs in the cytosol by which D-ribulose 5-phosphate becomes CMP-3-deoxy-D-manno-octulosonate (CMP-Kdo). Kdo is a component in the plant cell wall, specifically of pectic polysaccharide rhamnogalacturonan II. First, arabinose-5-phosphate isomerase catalyzes the conversion of D-ribulose 5-phosphate to D-arabinose 5-phosphate. Second, D-arabinose 5-phosphate is spontaneously converted into D-arabinofuranose 5-phosphate. Third, 3-deoxy-8-phosphooctulonate synthase converts D-arabinofuranose 5-phosphate into 3-deoxy-D-manno-octulosonate 8-phosphate (KDO-8P). This enzme is a homotetramer. Fourth, the predicted enzyme 3-deoxy-manno-octulosonate-8-phosphatase (coloured orange in the image) is theorized to catalyze the conversion of 3-deoxy-D-manno-octulosonate 8-phosphate (KDO-8P) into 3-deoxy-D-manno-2-octulosonate (Kdo). The last reaction is localized to the mitochondria outer membrane whereby 3-deoxy-manno-octulosonate cytidylyltransferase (coloured dark green in the image) catalyzes the conversion of 3-deoxy-D-manno-2-octulosonate (Kdo) into CMP-3-deoxy-D-manno-octulosonate (CMP-Kdo). This enzyme requires a magnesium ion as a cofactor.

Putrescine is an organic chemical produced when amino acids are broken down in organsisms, both living and dead. It can be used as a carbon and nitrogen source in E. coli, and is broken down into gamma-aminobutyric acid (GABA). In this pathway, GABA from putrescine degradation reacts with oxoglutaric acid in a reversible reaction catalyzed by 4-aminobutyrate aminotransferase. This reaction forms succinic acid semialdehyde, as well as L-glutamic acid as a byproduct. Succinic acid semialdehyde is then converted to succinic acid in a reaction catalyzed by succinate-semialdehyde dehydrogenase, using NAD as a cofactor. Succinic acid can then be used by the bacteria in the TCA cycle.

2,3-Dihydroxybenzoate, also known as 2-pyrochatechuic acid or hypogallic acid, is a phenol compound found in bacteria that can be a component of siderophores. These are compounds that strongly bind iron molecules and allow them to be taken up and used by the bacteria in cases of iron scarcity. An example of a siderophore in E. coli is enterobactin, which can be produced from 2,3-dihydroxybenzoate as part of the enterobactin biosynthesis pathway. In this pathway, chorismate, which is the product of the chorismate biosynthesis pathway, is converted to isochorismate in a reaction catalyzed by isochorismate synthase. Following this, a water molecule is added to isochorismate by isochorismatase, which then removes a pyruvic acid molecule as a byproduct, and forms (2S, 3S)-2,3-dihydroxy-2,3-dihydrobenzoate. Finally, 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase catalyzes the dehydrogenation of (2S, 3S)-2,3-dihydroxy-2,3-dihydrobenzoate into 2-pyrocatechuric acid (2,3-dihydroxybenzoate), using NAD as a cofactor. 2-Pyrocatechuric acid can then be used as a part of the enterobactin biosynthesis pathway, or it can be converted to 2-carboxymuconate by blue copper oxidase cueO.

Porphyrins are organic compounds. Many porphyrins are involved in oxygen transportation. Porphyrin ring biosynthesis begins in the mitochondria and involves glycine and succinyl-CoA condensation by δ-aminolevulinic acid synthase (ALAS) to produce δ-aminolevulinic acid (ALA), also known as 5-aminolevulinic acid. ALA is then transported to the cytosol where it becomes dimerized by ALA dehydratase (also known as porphobilinogen synthase) to produce porphobilinogen. The pathway continues with the condensation of 4 molecules of porphobilinogen catalyzed by porphobilinogen deaminase (PBG deaminase, also called hydroxymethylbilane synthase or uroporphyrinogen I synthase) to produce hydroxymethylbilane. Hydroxymethylbilane may then be converted to uroporphyrinogen III, a heme intermediate, or it may be non-enzymatically cyclized to uroporphyrinogen I. In the cytosol, uroporphyrinogen I and III substituents become decarboxylated to become coproporphyrinogens. Coproporphyrinogen III is an important intermediate in the synthesis of heme. In the inner mitochondria, coproporphyrinogen III undergoes decarboxylation of 2 propionate residues producing protoporphyrinogen IX. Protoporphyrinogen IX oxidase converts protoporphyrinogen IX to protoporphyrin IX. The final reaction of heme synthesis is ferrochelatase catalyzing the insertion of iron into the ring, producing heme b. Heme is broken down when heme oxygenase opens the heme ring. This oxidation produces linear tetrapyrrole biliverdin, ferric iron (Fe3+), and carbon monoxide (CO). Biliverdin reductase then produces bilirubin.