Quantitative metabolomics services for biomarker discovery and validation.
Specializing in ready to use metabolomics kits.
Your source for quantitative metabolomics technologies and bioinformatics.

Filter by Pathway Type:

Showing 1 - 10 of 48701 pathways
SMPDB ID Pathway Chemical Compounds Proteins


Pw122411 View Pathway

2-Amino-3-Carboxymuconate Semialdehyde Degradation

This pathway is part of a major route of the degradation of L-tryptophan. It begins with 2-amino-3-carboxymuconate-6-semialdehyde which is generated from L-tryptophan degradation. The 2-amino-3-carboxymuconate-6-semialdehyde first is acted upon by a decarboxylase, forming 2-aminomuconic acid semialdehyde, which is then dehydrogenated by 2-aminomuconic semialdehyde dehydrogenase to form 2-aminomuconic acid. An unknown protein forms a 2-aminomuconate deaminase which forms (3E)-2-oxohex-3-enedioate, and a second unknown protein forms a 2-aminomuconate reductase, which forms oxoadipic acid from (3E)-2-oxohex-3-enedioate. Finally, within the mitochondria, oxoadipic acid is dehydrogenated and a coenzyme A is attached by the organelle’s oxoglutarate dehydrogenase complex, forming glutaryl-CoA. Glutaryl-CoA can then be further degraded.


Pw122406 View Pathway

Pancreas Function - Delta Cell

Pancreatic delta cells produce somatostatin which functions to inhibit glucagon, insulin, and itself. Somatostatin is stored in granules in the delta cell and is released in response to an increase in blood sugar, calcium, and blood amino acids during absorption of a meal. In the process of somatostatin secretion, glucose must first undergo glycolysis in the mitochondrion to increase ATP in the cell. The inside of the alpha cell then becomes electrically positive due to the closure of potassium channels that were inhibited by ATP. From this closure, the potassium is no longer being shuttled out of the cell, thus depolarizing the cell due to the extra intracellular potassium. The resulting action potential from the increased membrane potential causes the voltage gate calcium channels to open, creating an influx of calcium into the cell. This triggers the exocytosis of somatostatin granules from the delta cell.


Pw122401 View Pathway

Aldosterone from Steroidogenesis

Aldosterone is a hormone produced in the zona glomerulosa of the adrenal cortex. It's function is to act on the distal convoluted tubule and the collecting duct of the nephron to make them more permeable to sodium to allow for its reuptake (in addition to allowing potassium wasting). As a result, water follows the sodium back into the body. The water retention contributes to an increased blood volume. Angiotensin II from the circulation binds to receptors on the zona glomerulosa cell membrane, activating the G protein and triggering a signaling cascade. The end result is the activation of the steroidogenic acute regulatory (StAR) protein that permits cholesterol uptake into the mitochondria. From there, cholesterol undergoes a series of reactions in both the mitochondrion and the smooth endoplasmic reticulum (steroidogenesis) where it finally becomes aldosterone.


Pw122397 View Pathway

Eumelanin Biosynthesis

Melanin is the term used for multiple pigments found in many organisms, and specifically our skin, hair and iris tissues. There are three types of melanin, eumelanin, pheomelanin and neuromelanin. Eumelanin is the most common, and can be brown or black. Melanin is produced by melanocytes, and is a polymer made of smaller components, so there are many types with different polymerization patterns and proportions of components. To begin, this pathway takes L-dopachrome from the L-dopa and L-dopachrome biosynthesis pathways and, in the melanosome, it can either spontaneously form 5,6-dihydroxyindole, or can form 5,6-dihydroxyindole-2-carboxylic acid using L-dopachrome tautomerase as the catalyst. Both 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid use tyrosinase as a catalyst to form indole-5,6-quinone and indole-5,6-quinone-2-carboxylate respectively. Finally, some combination of 5,6-hydroxyindole, indole-5,6-quinone, 5,6-dihydroxyindole-2-carboxylic acid and indole-5,6-quinone-2-carboxylate combine to form melanochrome, an intermediate in the formation of eumelanin, and finally forms eumelanin, the final product of this pathway.


Pw122396 View Pathway

Arsenate Detoxification

Arsenate is a compound similar to phosphate, but containing an arsenic atom instead of the phosphorous. As such, it is treated similarly to a phosphate ion. However, if the arsenate replaces inorganic phosphates in glycolysis, it allows glycolysis to proceed, but does not generate ATP, uncoupling glycolysis. It can also bind to lipoic acid in the Krebs cycle, leading to a greater loss of ATP. Arsenate can enter into the cell via aquaporins 7 and 9, as well as facilitated glucose transporter members 1 and 4 of solute carrier family 2, and does so by diffusion. Once inside the cell, the arsenate can be converted to arsenite via the glutathione S-transferase omega-1 enzyme, or it can be converted to ribose-1-arsenate via the purine nucleoside phosphorylase. Ribose-1-arsenate then can spontaneously form arsenite through a reaction involving hydrogen and dihydrolipoate. After arsenite has been formed by either of these methods, arsenite methyltransferase catalyzes its formation into methylarsonate. From here, it forms methylarsonite via the glutathione S-transferase omega-1 enzyme again. The methylarsonite reacts with S-adenosylmethionine, catalyzed by arsenite methyltransferase, in order to become dimethylarsinate. Finally, the compound once again interacts with the glutathione S-transferase omega-1 enzyme to form dimethylarsinous acid, the final compound in this pathway.


Pw122328 View Pathway

Kandutsch-Russell Pathway (Cholesterol Biosynthesis)

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.


Pw122325 View Pathway

Bloch Pathway (Cholesterol Biosynthesis)

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 View Pathway

Mevalonate Pathway

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.


Pw122296 View Pathway

Pancreas Function - Alpha Cell

Alpha cells are a type of islet cell found in the pancreas that release glucagon. Glucagon counteracts insulin and functions to maintain glucose homeostasis when detected glucose levels are low. Glucagon is contained in granules in the cell as a reserve ready to be released. Extracellular glucose levels and ion channels regulate the secretion of glucagon. Glucose undergoes glycolysis to increase ATP in the cell. The moderate activity of potassium ATP channels causes the membrane potential to be around -70mV. The alpha cell then becomes electrically active due to the closure of potassium channels. The cell membrane becomes depolarized due to voltage dependent sodium, potassium and calcium channels. This causes an increase in action potentials and opens voltage gate calcium channels causing an increase of calcium into the cell. This triggers the exocytosis of glucagon from the cell. Conversely, an increase in extracellular glucose leads to an increase in ATP production and inhibition of potassium ATP channels. The membrane depolarizes to a membrane potential that inactivates voltage dependent calcium channels. This results in decreased intracellular calcium and inhibits exocytosis of glucagon.


Pw122285 View Pathway

Pancreas Function - Beta Cell

Beta cells are found in pancreatic islet cells and their main function is to release insulin. Insulin counteracts glucagon and functions to maintain glucose homeostasis when glucose levels are high. Insulin is contained in granules in the cell as a reserve ready to be released, which is dependent on extracellular glucose levels, and intracellular calcium levels and/or various proteins that activate the vesicle-associated membrane protein on the insulin granules' membranes. In the process of insulin secretion, glucose must first undergo glycolysis to increase ATP in the cell. The inside of the beta cell then becomes electrically positive due to the closure of potassium channels that were inhibited by ATP. From this closure, the potassium is no longer being shuttled out of the cell, thus depolarizing the cell due to the extra intracellular potassium. The resulting action potential from the increased membrane potential causes the voltage gate calcium channels to open, creating an influx of calcium into the cell. This triggers the vesicle-associated membrane protein on the outside of the insulin granule to tether, dock, and fuse with the beta cell membrane. Insulin is then exocytosed from the cell. However, the vesicle-associated membrane protein can be activated by other means in addition to calcium. Acetylcholine can bind to muscarinic acetylcholine receptors on the cell membrane and trigger a G protein cascade. This eventually leads to the activation of inositol trisphosphate to cause calcium release from the rough endoplasmic reticulum so that it can activate the calcium/calmodulin-dependent protein kinase to trigger the vesicle-associated membrane protein. The G protein cascade can also lead to the activation of diacylglycerol and subsequently protein kinase C to lead to the same outcome. Glucagon-like peptide can also trigger a similar G protein cascade when it binds to glucagon-like peptide receptors on the cell membrane of the beta cell. This process involves cAMP and a few other proteins in order to lead to the same eventual outcome of triggering the vesicle-associated membrane protein and the exocytosis of insulin from the beta cell.
Showing 1 - 10 of 48701 pathways