Browsing Pathways

From glycolysis and the mevalonate pathway, diphosphomevalonic acid can be reacted with ATP to produce isopentenyl diphosphate which can be used in many reactions due to it's phosphate groups. Isopentenyl can be converted into geranyl pyrophosphate through two different paths, with one having an intermediate of dimethylallylpyrophosphate. Geranyl pyrophosphate itself can be used in monoterpenoid biosynthesis but more importantly, it can converted into (E,E)- farnesyl diphosphate through farnesyl pyrophosphate synthase. With (E,E)-farnesyl diphosphate and isopentenyl diphosphate, many reactions can take place depending on the number of substrates are used and how many phosphate groups are to be transferred. The products from the reactions are usually substrates for other biosynthesis pathways like N-glycan biosynthesis, carotenoid biosynthesis, diterpenoid biosynthesis, steroid biosynthesis and ubiquinone and other terpenoid quinone biosynthesis pathways. (E,E) farnesyl diphosphate can also be combined with a cysteine protein to make S-farnesyl protein. S-Farnesyl protein can have the c-terminal removed and then can be trans methylated by S-adenosylmethionine to eventually make farnesylcysteine. Through unknown processes farnesylcysteine can be converted can converted back to (E,E) farnesyl diphosphate, but not all the enzymes are known yet.

Phenylpropanoid biosynthesis is responsible for creating large amounts of secondary metabolites from many different intermediates from other pathways such as the shikimate pathway. The biosynthesis has many different reductases, oxygenases and transferases which help create the specific secondary metabolites necessary for characteristic plant development. From L-phenylalanine, cinnamic acid and cinnamoyl-CoA are products which can further create coumaroyl-CoA, an important metabolite with feeds into all downstream reactions for other metabolites. Downstream metabolites caffeic acid, ferulic acid, 5-hydroxyferulic acid, and sinapic acid can all be reduced into their CoA, aldehyde and aldehyde form through similar enzymes and can be converted between each other as well. All the alcohols at the end can feed into lignin biosynthesis, which is important for plant structure. The metabolites cinnamoyl-CoA and p-coumaroyl-CoA can feed into flavonoid, stillnenoid, diarylhe paranoid and gingerol biosynthesis.

Thiamine is used in a variety of metabolic pathways in the form of thiamine pyrophosphate, or Vitamin B1. Its use is primarily as a cofactor for enzymes in key metabolic reactions. In plants, 5-aminoimidazole ribonucleotide, a product from purine metabolism, reacts with S-adenosylmethionine to produce 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate in the chloroplast. With the help of a TH1 enzyme, this compound reacts to form 4-amino-5-hydroxymethyl-2-methylpyrimidine diphosphate, dephosphorylating ATP in the process. This diphosphate compound is then further broken down into thiamine monophosphate by reacting with a number of complex compounds, two of which are derived from reactions using Glycine and 5-(2-hydroxymethyl)-4-methylthiazole, respectively. The thiamine monophosphate is then transported out of the chloroplast into the cytoplasm, where it is hydrolysed to form thiamine. Thiamine is now phosphorylated through a pair of reactions to form thiamine triphosphate. Alternatively, thiamine undergoes unknown reaction(s) to form N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine, which, after being hydrolysed twice, is transported back into the chloroplast and reacts to form the earlier compound 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate. Notedly, many of the compounds used in thiamine metabolism are modified products of other crucial metabolic pathways, including glycine metabolism, cysteine metabolism, and glycolysis.

Zeatin encourages lateral bud growth, resulting in bushier plants. It stimulates cell division when sprayed on meristems. Terpenoid backbone biosynthesis produces dimethylallyl diphosphate which, with different reactants, can result in different products with a byproduct of diphosphate. When reacted with tRNA adenine via tRNA dimethylallyltransferase, it results in the formation of tRNA containing 6-isopentenyl adenosine. When reacted via adenylate isopentenyltransferase 1, chloroplastic with either ATP, ADP, or AMP, it results in the formation of the corresponding isopentenyl, which in turn reacts with oxygen and reduced NADPH hemoprotein reductase via cytokinin hydroxylase, resulting in the formation of trans-zeatin riboside with the corresponding phosphates and byproducts of water and oxidized NADPH hemoprotein reductase.

Xylene is a common aromatic hydrocarbon used in the medical industry as a solvent. This pathway describes a part of how xylene is degraded in certain bacterial species. Xylene exists in different percentages in a laboratory-grade level and is of a few common kinds: m-xylene (40–65%), p-xylene (20%), o-xylene (20%) and ethylbenzene (6-20%) and traces of toluene, trimethyl benzene, phenol, thiophene, pyridine, and hydrogen sulfide. In the bigger picture of this pathway, m-xylene, p-xylene, o-xylene as well as toluene are considered, where part of the degradation processes for each of these xylene types have been illustrated. All degradation reactions here are taking place in the cytoplasm. One part of this pathway starts with 4-methylbenzoic acid / p-methylbenzoate which is a product downstream of the p-xylene degradation and forms other intermediates: cis-1,2-dihydroxy-4-methylcyclohexa-3,5-diene-1-carboxylate, 4-methylcatechol, 3-methyl-cis,cis-muconate, 4-methylmuconolactone and 3-methylmuconolactone aided by the proteins and protein complexes: toluate-1,2-deoxygenase alpha and beta subunit, cis-1,2-dihydroxycyclohexa-3,4-diene carboxylate dehydrogenase, catechol 1,2-dioxygenase, and muconate cycloisomerase I. It must be noted that the intermediate 3-methyl-cis,cis-muconate gives rise to two products in this pathway via two different reactions using the same protein muconate cycloisomerase I. The other section of this pathway demonstrates the degradation of o-methylbenzoate and m-methylbenzoate. o-Methylbenzoae degrades down to the intermediate 1,2-dihydroxy-6-methylcyclohexa-3,5-dienecarboxylate and m-methylbenzoate degrades down to the intermediate 1,2-dihydroxy-3-methylcyclohexa-3,5-dienecarboxylate. They both then degrade to the same product/intermediate 3-methylcatechol. These reactions are both catalyzed by the proteins probable ring-hydroxylating dioxygenase subunit and cis-1,2-dihydroxycyclohexa-3,4-diene carboxylate dehydrogenase respectively.

Phenylalanine is reduced into different substrates like tyrosine, which can be further metabolized or substrates that feed into catabolic processes like the citric acid cycle and glycolysis. L-Phenylalanine is reduced to phenylethylamine via L-amino-acid decarboxylase releasing carbon dioxide. Phenylethylamine is further reduced into phenylacetaldehyde by monoamine oxidase on the hepatocyte plasma membrane to give phenylacetaldehyde. Phenylacetaldehyde can be metabolized further into phenylacetic acid through another hepatocyte membrane enzyme aldehyde dehydrogenase.

This pathway consists of two major interconversions, those of pentose and those of glucuronate. A pentose is an important monosaccharide involved in amino sugar and nucleotide sugar metabolism, the pentose phosphate pathway, and more biochemically relevant synthesis pathways. Glucuronate (D-glucuronic acid) is a carboxylic acid that is highly soluble in water and can link to many compounds in transport and elimination processes (glucuronidation). Its metabolic pathway begins with glucose 1-phosphate (G1P, a naturally occurring Cori ester consisting of a glucose molecule with a phosphate group on the 1'-carbon) from glycolysis. G1P is converted to uridine diphosphate glucose (UDP-glucose) via a reaction catalysed by a transferase enzyme. UDP-Glucose can also enter this pathway from galactose metabolism. An oxidoreductase then catalyses the conversion of UDP-glucose into UDP-glucuronate, which can form a glucuronide via a glucuronosyltransferase-catalysed reaction. In fruit fly glucuronate interconversion, there is one bidirectional enzyme characterized (EC 2.4.1.17, experimental evidence in UniProt) that converts UDP-glucuronate into beta-D-glucuronoside and two experimental enzymes that catalyse the reaction of UDP-glucuronate into D-glucuronate 1-phosphate (the latter two are not included in this pathway for brevity). A beta-glucuronidase then catalyses the conversion of beta-D-glucuronoside into glucuronic acid, which can either feed into inositol phosphate metabolism or be converted into L-gulonate in a reaction aided by NADP-dependent alcohol dehydrogenase. L-Gulonate is converted into 3-dehydro-L-gulonate via an oxideoreducatase-catalysed reaction, which can then form L-xylulose in a reaction involving an unknown enzyme. This ketose can feed into amino sugar and nucleotide sugar metabolism once converted into L-arabitol and subsequently into L-arabinose. Arabinose also feeds into ribulose formation. Pentose interconversion (via L-ribulose) is inferred but not yet characterized in Drosophila melanogaster (see KEGG for pathway details). Alternatively, xylulose, upon conversion into xylitol in a reaction catalysed by L-xylulose reductase, can feed into pentose interconversion, the pentose phosphate pathway, and pyruvate production. Currently, many enzymes involved in pentose interconversion have yet to be characterized in the common fruit fly, but its metabolites feed into the TCA Cycle, among other metabolic pathways, including those of glucuronate interconversion. One such compound is D-xylonolactone, which can both feed into the citrate cycle and produce pyruvate. Another enzyme to note is L-iditol 2-dehydrogenase, which is a widely-distributed enzyme that has been described in archaea, bacteria, yeast, plants and animals. It acts on a number of sugar alcohols, including (but not limited to) L-iditol, D-glucitol, D-xylitol, and D-galactitol. Enzymes from different organisms or tissues display different substrate specificity. The enzyme is specific to NAD+ and cannot use NADP+. In pentose and glucuronate interconversions, this enzyme catalyses the conversion of D-xylitol into D-xylulose. This ketopentose product is then phosphorylated (in a reaction catalysed by xylulokinase), forming xylulose 5-phosphate. The epimerase that converts xylulose 5-phosphate into ribulose 5-phosphate also catalyses the conversion of D-erythrose 4-phosphate into D-erythrulose 4-phosphate and D-threose 4-phosphate. D-Ribulose-5-phosphate feeds into the pentose phosphate pathway. This pathway contains many reversible enzyme-regulated reactions.