Pathways

PathWhiz ID Pathway Meta Data

PW122333

Pw122333 View Pathway
metabolic

Drosopterin and Aurodrosopterin Biosynthesis

Drosophila melanogaster
Drosopterin and aurodrosopterin are two of the 5 or more red pigment components involved in Drosophila eye color. Both are similar compounds, with aurodrosopterin lacking an amino group compared to drosopterin. Their synthesis starts with GTP, which is hydrolyzed by GTP cyclohydrolase to form 7,8-dihydroneopterin 3'-triphosphate. 7,8-dihydroneopterin 3'-triphosphate then has its triphosphate group cleaved by 6-pyruvoyl-tetrahydropterin synthase to form (6R)-6-pyruvoyl-5,6,7,8-tetrahydropterin (dyspropterin). A currently unknown reaction occurs to convert dyspropterin to 7,8-dihydropterin during which a side-chain is removed. This reaction could be spontaneous or enzyme catalyzed. From there, 7,8-dihydropterin is deaminated by 7,8-dihydropterin deaminase, forming 7,8-dihydrolymazine. Dyspropterin is also catalyzed by pyrimidodiazepine synthase to form 2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido[4,5-b][1,4]diazepin-4-one (pyrimidodiazepine). Pyrimidodiazepine can spontaneously react with either 7,8-dihydropterin to form drosopterin, or 7,8-dihydrolymazine to form aurodrosopterin, which is the final product of this pathway.

PW122332

Pw122332 View Pathway
metabolic

Juvenile Hormone Synthesis

Drosophila melanogaster
Juvenile hormones in insects are important for their growth before their adulthood, preventing metamorphosis if they undergo one. In Drosophila, only Juvenile Hormone III has been identified, while others exist in butterflies and moths. Synthesis of various forms of Juvenile Hormone III (JH III) start with farnesyl diphosphate interacting with an uncharacterized phosphatase protein, forming farnesol. Farnesol then interacts with NADP+ dependent farensol dehydrogenase, which removes a hydrogen ion from the hydroxyl group in order to form farnesal. Farnesal then enters the mitochondria and interacts with another uncharacterized aldehyde dehydrogenase which allows it to form farnesoic acid. Farnesoic acid can then interact with an unknown protein, similar to farnesoate epoxidase in Bombyx mori, in order to form Juvenile Hormone III acid (JH III acid). JH III acid can then itneract with epoxide hydrolase in the membrane of the endoplasmic reticulum, forming the final product of this pathway, Juvenile Hormone III acid diol (JH III acid diol). It can also interact with Juvenile Hormone acid O-methyltransferase in order to form Juvenile Hormone III (JH III), which is used in another set of reactions in this pathway. If farnesoic acid does not interact with the unknown protein, it may interact with Juvenile Hormone acid O-methyltransferase to form methyl farnesoate. Methyl farnesoate can then interact with a different unknown protein similar, to methyl farnesoate epoxidase in Diploptera punctata, in order to form JH III. In the mitochondria, JH III can interact with carboxylic ester hydrolase in order to form JH III acid, which then can form the final product, or form JH III again. Alternately, JH III can interact with epoxide hydrolase in the membrane of the endoplasmic reticulum, forming Juvenile Hormone III diol (JH III diol). This product then interacts with carboxylic ester hydrolase in the mitochondria, forming JH III acid diol, again, the end product of this pathway.

PW122329

Pw122329 View Pathway
metabolic

Molting Hormone Biosynthesis

Drosophila melanogaster
20-hydroxyecdysone is a steroid hormone that controls the ecdysis or molting of insects. It is formed from the modification of cholesterol by various p450 enzymes. Initially, cholesterol is modified by a cholesterol 7-desaturase, forming 7-dehydrocholesterol. In the endoplasmic reticulum, 7-dehydrocholesterol is modified by cytochrome p450 307a1 to form diketol. Diketol can interact with the cytochrome p450 306a1 enzyme, ecdysteroid 25-hydroxylase, forming 2,22-dideoxy-3-dehydroecdysone. In the mitochondria, 2,22-dideoxy-3-dehydroecdysone can be modified by cytochrome p450 302a1, also known as ecdysteroid 22-hydroxylase, which forms 3-dehydro-2-deoxyecdysone, which in turn can be modified by cytochrome p450 315a1, ecdysteroid 2-hydroxylase, to form 3-dehydroecdysone, one of the final products of this pathway. Diketol can also spontaneously form 3β,5β-ketodiol, which then interacts with the same enzymes as diketol. First, it is modified in the endoplasmic reticulum by cytochrome p450 306a1, ecdysteroid 25-hydroxylase to form 3β,5β-ketotriol. In the mitochondria, 3β,5β-ketotriol is then modified by cytochrome p450 302a1, ecdysteroid 22-hydroxylase, to form 2-deoxyecdysone, and then cytochrome 315a1, ecdysteroid 2-hydroxylase, to form ecdysone. From this point, ecdysone can interact with ecdysone oxidase to form 3-dehydroecdysone, the same product as in the first half of this pathway. In addition to this reaction, ecdysone can also interact with ecdysone 20-monooxygenase in the mitochondria to form 20-hydroxyecdysone (crustecdysone), which is the main molting hormone. Finally, 20-hydroxyecdysone can interact with cytochrome p450 18a1, 26-hydroxylase, in order to form 20,26-dihydroxyecdysone, the final product of this branch of the pathway.

PW122328

Pw122328 View Pathway
metabolic

Kandutsch-Russell Pathway (Cholesterol Biosynthesis)

Homo sapiens
The Kandutsch-Russell pathway is the alternative pathway stemming from the mevalonate pathway completing cholesterol biosynthesis. The Bloch pathway and the Kandutsch-Russell pathway are both key to a functioning human body as cholesterol aids in the development of many important nutrients and hormones, such as vitamin D. Starting in the endoplasmic reticulum, lanosterol is the first compound used in this pathway, and when catalyzed by delta(24)-sterol-reductase, becomes 24,25-dihydrolanosterol. 24,25-Dihydrolanosterol is quickly converted to 4,4-dimethyl-14a-hydroxymethyl-5a-cholesta-8-en-3b-ol with the help of the enzyme lanosterol 14-alpha demethylase. This same enzyme, lanosterol 14-alpha demethylase, is also responsible for the conversion of 4,4-dimethyl-14a-hydroxymethyl-5a-cholesta-8-en-3b-ol into 4,4-dimethyl-14a-formyl-5a-cholest-8-en-3b-ol. Lanosterol 14alpha demethylase is used once more here, to push the pathway into the inner nuclear membrane, converting 4,4-dimethyl-14a-formyl-5a-cholest-8-en-3b-ol into 4,4-dimethyl-5a-cholesta-8,14-dien-3b-ol. Now located in the inner nuclear membrane, 4,4-dimethyl-5a-cholesta-8,14-dien-3b-ol is converted into 4,4-dimethyl-5a-cholesta-8-en-3b-ol through the help of a lamin-b receptor. Entering the endoplasmic reticulum membrane, methylsterol monooxygenase 1 is used to convert 4,4-dimethyl-5a-cholesta-8-en-3b-ol into 4a-hydroxymethyl-4b-methyl-5a-cholesta-8-en-3b-ol. 4a-Hydroxymethyl-4b-methyl-5a-cholesta-8-en-3b-ol then uses methylsterol monooxygenase 1 to become 4a-formyl-4b-methyl-5a-cholesta-8-en-3b-ol. Once again, methylsterol monooxygenase 1 is used to convert 4a-formyl-4b-methyl-5a-cholesta-8-en-3b-ol into 4a-carboxy-4b-methyl-5a-cholesta-8-en-3b-ol. Now using sterol-4-alpha-carboxylate 3-dehydrogenase, 4a-carboxy-4b-methyl-5a-cholesta-8-en-3b-ol is turned into 4a-methyl-5a-cholesta-8-en-3-one. This puts the pathway in the cell membrane, where a 3-keto-steroid reductase is used to convert 4a-methyl-5a-cholesta-8-en-3b-one into 4a-methyl-5a-cholesta-8-en-3-ol. Moving back into the endoplasmic reticulum membrane, methylsterol monooxygenase 1 converts 4a-methyl-5a-cholesta-8-en-3-ol into 4a-hydroxymethyl-5a-cholesta-8-en-3b-ol. Methylsterol monooxygenase is used twice more in this pathway, first converting 4a-hydroxymethyl-5a-cholesta-8-en-3b-ol into 4a-formyl-5a-cholesta-8-en-3b-ol, then converting 4a-formyl-5a-cholesta-8-en-3b-ol into 4a-carboxy-5a-cholesta-8-en-3b-ol. Now using sterol-4-alpha-carboxylate 3 dehydrogenase, 4a-carboxy-5a-cholesta-8-en-3b-ol becomes 5a-cholesta-8-en-3-one and brings the pathway back to the cell membrane. 5a-Cholesta-8-en-3-one teams up with a 3-keto-steroid reductase to create 5a-cholest-8-en-3b-ol. Then, stepping back into the endoplasmic reticulum membrane, 5a-cholest-8-en-3b-ol enlists the help of 3-beta-hydroxysteroid-delta(8),delta(7)-isomerase to produce lathosterol. Lathosterol and lathosterol oxidase work together to make 7-dehydrocholesterol . Finally, 7-dehydrocholesterol partners with 7-dehydrocholesterol reductase to create cholesterol, completing the final step in cholesterol biosynthesis.

PW122326

Pw122326 View Pathway
drug action

Piroxicam Action Action Pathway Xuan (Demo Purpose) 2

Homo sapiens

PW122325

Pw122325 View Pathway
metabolic

Bloch Pathway (Cholesterol Biosynthesis)

Homo sapiens
The Bloch pathway, named after Konrad Bloch, is the pathway following the mevalonate pathway occurring within the cell to complete cholesterol biosynthesis. Cholesterol is a necessary metabolite that helps create many essential hormones within the human body. This pathway, combined with the mevalonate pathway is one of two ways to biosynthesize cholesterol; the Kandutsch-Russell pathway is an alternative pathway that uses different compounds than the Bloch Pathway beginning after lanosterol. The first three reactions occur in the endoplasmic reticulum. Lanosterol, a compound created through the mevalonate pathway, binds with the enzyme lanosterol 14-alpha demethylase to become 4,4-dimethyl-14a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol. Moving to the next reaction, 4,4-dimethyl-14a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol utilizes the enzyme lanosterol 14-alpha demethylase to create 4,4-dimethyl-14α-formyl-5α-cholesta-8,24-dien-3β-ol. Lanosterol 14-alpha demethylase is used one last time in this pathway, converting 4,4-dimethyl-14α-formyl-5α-cholesta-8,24-dien-3β-ol into 4,4-dimethyl-5a-cholesta-8,14,24-trien-3b-ol. Entering the inner nuclear membrane, 4,4-dimethyl-5a-cholesta-8,14,24-trien-3b-ol is catalyzed by a lamin B receptor to create 4,4-dimethyl-5a-cholesta-8,24-dien-3-b-ol. Entering the endoplasmic reticulum membrane, 4,4-dimethyl-5a-cholesta-8,24-dien-3-b-ol, with the help of methyl monooxygenase 1 is converted to 4a-hydroxymethyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol. The enzyme methyl monooxygenase 1 uses 4a-hydroxymethyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol to produce 4a-formyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol. This reaction is repeated once more, using 4a-formyl-4b-methyl-5a-cholesta-8,24-dien-3b-ol and methyl monooxygenase 1 to create 4a-carboxy-4b-methyl-5a-cholesta-8,24-dien-3b-ol. Briefly entering the endoplasmic reticulum, 4a-carboxy-4b-methyl-5a-cholesta-8,24-dien-3b-ol then uses sterol-4-alpha-carboxylate-3-dehyrogenase to catalyze into 3-keto-4-methylzymosterol. Back in the endoplasmic reticulum membrane, where the pathway will continue on for the remaining reactions, 3-keto-4-methylzymosterol combines with 3-keto-steroid reductase to create 4a-methylzymosterol. 4a-Methylzymosterol joins the enzyme methylsterol monooxgenase 1 to result in 4a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol. 4a-Hydroxymethyl-5a-cholesta-8,24-dien-3b-ol uses methylsterol monooxygenase 1 to convert to 4a-formyl-5a-cholesta-8,24-dien-3b-ol. 4a-Formyl-5a-cholesta-8,24-dien-3b-ol proceeds to use the same enzyme used in the previous reaction: methylsterol monooxygenase 1, to catalyze into 4a-carboxy-5a-cholesta-8,24-dien-3b-ol. Sterol-4-alpha-carboxylate-3-dehydrogenase is used alongside 4a-carboxy-5a-cholesta-8,24-dien-3b-ol to produce 5a-cholesta-8,24-dien-3-one (also known as zymosterone). Zymosterone (5a-cholesta-8,24-dien-3-one) teams up with 3-keto-steroid reductase to create zymosterol. Zymosterol proceeds to use the enzyme 3-beta-hydroxysteroid-delta(8),delta(7)-isomerase to catalyze into 5a-cholesta-7,24-dien-3b-ol. The compound 5a-cholesta-7,24-dien-3b-ol then joins lathosterol oxidase to convert to 7-dehydrodesmosterol. 7-Dehydrodesmosterol and the enzyme 7-dehydrocholesterol reductase come together to create desmosterol. This brings the pathway to the final reaction, where desmosterol combines with delta(24)-sterol reductase to finally convert to cholesterol.

PW122323

Pw122323 View Pathway
metabolic

Mevalonate Pathway

Homo sapiens
The Mevalonate Pathway is a necessary pathway that occurs in archaea, eukaryotes and select bacteria. It has mainly been studied with regard to cholesterol biosynthesis and how it relates to cardiovascular disease in humans, but has recently garnered attention for its many other essential roles within human pathology. The pathway begins in the cytoplasm with acetyl-CoA and acetoacetyl-CoA, which interact with acetyl-CoA acetyltransferase, coenzyme A and water to synthesize hydroxymethylglutaryl-CoA synthase. In turn, this synthase teams up with coenzyme A and a hydrogen ion in the endoplasmic reticulum to create 3-hydroxy-3-methylglutaryl-CoA. 3-Hydroxy-3-methylglutaryl-CoA then pairs with 2NADPH, 2 hydrogen ions and is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase to produce (R)-mevalonate, also producing byproducts CoA and NADP. Exiting the endoplasmic reticulum, and entering the peroxisome, (R)-mevalonate uses the help of ATP and mevalonate kinase to create mevalonic acid (5P). This piece is especially important to the human species as decreased activity of the enzyme mevalonate kinase has been found to be a direct link to two auto-inflammatory disorders: MVA and HIDS. Using phosphomevalonate kinase and ATP, the pathway re-enters the cytoplasm and mevalonic acid (5P) converts to (R)-mevalonic acid-5-pyrophosphate and ADP. (R)-mevalonic acid-5-pyrophosphate, ATP and diphosphomevalonate decarboxylase work together to create phosphate, carbon dioxide, ADP and isopentenyl pyrophosphate. Re-entering the peroxisome, isopentenyl diphosphate delta isomerase 1 is waiting to propel isopentenyl pyrophosphate into dimethylallylpyrophosphate. This pushes the pathway back into the cytoplasm, where another isopentenyl pyrophosphate molecule and the enzyme farnesyl pyrophosphate synthase create pyrophosphate and geranyl-PP. Yet another isopentenyl pyrophosphate molecules works with farnesyl pyrophosphate synthase to produce pyrophosphate and farnesyl pyrophosphate. Now in the endoplasmic reticulum membrane, 2 farnesyl pyrophosphate molecules with the help of NADPH and a hydrogen ion catalyze with squalene synthase and create squalene. This is an important first step in the specific hepatic cholesterol pathway. Remaining in the endoplasmic reticulum membrane, squalene, FMNH, oxygen and squalene monooxygenase synthesize (S)-2,3-epoxysqualene. This comes along with the byproducts of flavin mononucleotide, a hydrogen ion and water. In the final reaction within this pathway, lanesterol synthase converts (S)-2,3-epoxysqualene to lanosterin. Not pictured in this pathway, lanosterin will eventually be converted to cholesterol, an important part of many functions in the human body.

PW122313

Pw122313 View Pathway
metabolic

try

Escherichia coli (strain K12)

PW122312

Pw122312 View Pathway
metabolic

Biosynthesis of siderophore group nonribosomal peptide

Lysinibacillus xylanilyticus t26
Siderophores are an important group of structurally diverse natural products that play key roles in ferric iron acquisition in most microorganisms. Two major pathways exist for siderophore biosynthesis. One is dependent on nonribosomal peptide synthetase (NRPS) multienzymes. The enzymology of several NRPS-dependent pathways to structurally diverse siderophores has been intensively studied for more than 10 years and is generally well understood. The other major pathway is NRPS-independent. It relies on a novel family of synthetase enzymes that until recently has received very little attention.

PW122311

Pw122311 View Pathway
metabolic

Beta-oxidation

Homo sapiens