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 101 - 110 of 48700 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0000065

Pw000039 View Pathway
Metabolic

Ubiquinone Biosynthesis

Ubiquinone is also known as coenzyme Q10. It is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits. Ubiquinone is a carrier of hydrogen atoms (protons plus electrons) and functions as an ubiquitous coenzyme in redox reactions, where it is first reduced to the enzyme-bound intermediate radical semiquinone and in a second reduction to ubiquinol (Dihydroquinone; CoQH2). Ubiquinone is not tightly bound or covalently linked to any known protein complex but is very mobile. In eukaryotes ubiquinones were found in the inner mito-chondrial membrane and in other membranes such as the endoplasmic reticulum, Golgi vesicles, lysosomes and peroxisomes. The benzoquinone portion of Coenzyme Q10 is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is also used for the first steps of cholesterol biosynthesis. The enzyme para-hydroxybenzoate polyprenyltransferase catalyzes the condensation of p-hydroxybenzoate with polyprenyl diphosphate to generate ubiquinone.

SMP0000466

Pw000154 View Pathway
Metabolic

Transfer of Acetyl Groups into Mitochondria

Acetyl-CoA is an important molecule, which is precursor to HMG CoA, which is a vital component in cholesterol and ketone synthesis. Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Acetyl-CoA is made in the mitochondria by metabolizing fatty acids, and the oxidation of pyruvate of acetyl-CoA. When the body has an excess of ATP, the energy in acetyl-Coa can be stored in the form of fatty acids. Acetyl-CoA must cross the mitochondrial membrane to the cytosol, where fatty acid synthesis takes place. Acetyl-CoA is combined with oxalacetic acid by the enzyme citrate synthase, creating citric acid. Citric acid is then transported out of the mitochondria, to the cytosol, where the enzyme citrate lyase converts citric acid back into acetyl-CoA and oxalacetic acid. Malate dehydrogenase reduces oxalacetic acid to malate, which then is either transported back into the mitochondria by the malate-alpha ketoglutarate transporter or oxidized to pyruvate by malic enzyme. Pyruvate can then be transported back into the mitochondria and undergo decarboxylation into oxalacetic acid. Malate can also be used to create NADH by the conversion of malate to oxalacetic acid by malate dehydrogenase.

SMP0000654

Pw000630 View Pathway
Metabolic

Warburg Effect

The Warburg Effect refers to the phenomenon that occurs in most cancer cells where instead of generating energy with a low rate of glycolysis followed by oxidizing pyruvate via the Krebs cycle in the mitochondria, the pyruvate from a high rate of glycolysis undergoes lactic acid fermentation in the cytosol. As the Krebs cycle is an aerobic process, in normal cells lactate production is reserved for anaerobic conditions. However, cancer cells preferentially utilize glucose for lactate production via this “aerobic glycolysis”, even when oxygen is plentiful. The Warburg Effect is thought to be the result of mutations to oncogenes and tumour suppressor genes. It may be an adaptation to low-oxygen environments within tumors, the result of cancer genes shutting down the mitochondria, or a mechanism to aid cell proliferation via increased glycolysis. The Warburg Effect involves numerous pathways, including growth factor stimulation, transcriptional activation, and glycolysis promotion.

SMP0000478

Pw000457 View Pathway
Metabolic

Nucleotide Excision Repair

In order to pass genetic information from one generation to the next, all organisms must accurately replicate their genomes during each cell division. This includes the nuclear genome and mitochondrial and chloroplast genomes. These are normally replicated with high fidelity that is achieved through the action of accurate DNA repair. Nucleotide Excision Repair is one os several mechanisms of DNA repair. Nucleotide excision repair (NER) operates on base damage caused by exogenous agents (such as mutagenic and carcinogenic chemicals and photoproducts generated by sunlight exposure) that cause alterations in the chemistry and structure of the DNA duplex . Such damage is recognized by a protein called XPC, which is stably bound to another protein called HHRAD23B (R23). The binding of the XPC–HHRAD23 heterodimeric subcomplex is followed by the binding of several other proteins (XPA, RPA, TFIIH and XPG). Of these, XPA and RPA are believed to facilitate specific recognition of base damage. TFIIH is a subcomplex of the RNA polymerase II transcription initiation machinery which also operates during NER. It consists of six subunits and contains two DNA helicase activities (XPB and XPD) that unwind the DNA duplex in the immediate vicinity of the base damage. This local denaturation generates a bubble in the DNA, the ends of which comprise junctions between duplex and single-stranded DNA. The subsequent binding of the ERCC1–XPF heterodimeric subcomplex generates a completely assembled NER multiprotein complex. XPG is a duplex/single-stranded DNA endonuclease that cuts the damaged strand at such junctions 3’ to the site of base damage. Conversely, the ERCC1–XPF heterodimeric protein is a duplex/single-stranded DNA endonuclease that cuts the damaged strand at such junctions 5’ to the site of base damage. This bimodal incision generates an oligonucleotide fragment 27–30 nucleotides in length which includes the damaged base. This fragment is excised from the genome, concomitant with restoring the potential 27–30 nucleotide gap by repair synthesis. Repair synthesis requires DNA polymerases or , as well as the accessory replication proteins PCNA, RPA and RFC. The covalent integrity of the damaged strand is then restored by DNA ligase. Collectively, these biochemical events return the damaged DNA to its native chemistry and configuration. ERCC1, excision repair cross-complementing 1; PCNA, proliferating cell nuclear antigen; POL, polymerase; RFC, replication factor C; RPA, replication protein A; TFIIH, transcription factor IIH; XP, xeroderma pigmentosum.

SMP0000589

Pw000565 View Pathway
Physiological

Gastric Acid Production

Gastric acid plays a key role in the digestion of proteins by activating digestive enzymes to break down long chains of amino acids. In addition, it aids in the absorption of certain vitamins and minerals and also acts as one of the body's first line of defence by killing ingested micro-organisms. This digestive fluid is formed in the stomach (specifically by the parietal cells) and is mainly composed of hydrochloric acid (HCl). However, it is also constituted of potassium chloride (KCl) and sodium chloride (NaCl). The main stimulants of acid secretion are histamine, gastrin, and acetylcholine which all, after binding to their respective receptors on the parietal cell membrane, trigger a G-protein signalling cascade that causes the activation of the H+/K+ ATPase proton pump. As a result, hydrogen ions are able to be pumped out of the parietal cell and into the lumen of the stomach. The hydrogen ions are available inside the parietal cell after water and carbon dioxide combine to form carbonic acid(the reaction is catalyzed by the carbonic anhydrase enzyme) which dissociates into a bicarbonate ion and a hydrogen ion. Moreover, the chloride and potassium ions are transported into the stomach lumen through their own channels so that hydrogen ions and/or potassium ions can form an ionic bond with chloride ions to form HCl and/or KCl, which are both constituents of stomach acid. In addition, the peptide hormone somatostatin is the main inhibitor to gastric acid secretion. Not only does it inhibit the G-protein signalling cascade that leads to proton pump activation, but it also directly acts on the enterochromaffin-like cells and G cells to inhibit histamine and gastrin release, respectively.

SMP0000452

Pw000166 View Pathway
Metabolic

Threonine and 2-Oxobutanoate Degradation

2-oxobutanoate, also known as 2-Ketobutyric acid, is a 2-keto acid that is commonly produced in the metabolism of amino acids such as methionine and threonine. Like other 2-keto acids, degradation of 2-oxobutanoate occurs in the mitochondrial matrix and begins with oxidative decarboxylation to its acyl coenzyme A derivative, propionyl-CoA. This reaction is mediated by a class of large, multienzyme complexes called 2-oxo acid dehydrogenase complexes. While no 2-oxo acid dehydrogenase complex is specific to 2-oxobutanoate, numerous complexes can catalyze its reaction. In this pathway the branched-chain alpha-keto acid dehydrogenase complex is depicted. All 2-oxo acid dehydrogenase complexes consist of three main components: a 2-oxo acid dehydrogenase (E1) with a thiamine pyrophosphate cofactor, a dihydrolipoamide acyltransferase (E2) with a lipoate cofactor, and a dihydrolipoamide dehydrogenase (E3) with a flavin cofactor. E1 binds the 2-oxobutanoate to the lipoate on E2, which then transfers the propionyl group to coenzyme A, producing propionyl-CoA and reducing the lipoate. E3 then transfers protons to NAD in order to restore the lipoate. Propionyl-CoA carboxylase transforms the propionyl-CoA to S-methylmalonyl-CoA, which is then converted to R-methylmalonyl-CoA via methylmalonyl-CoA epimerase. In the final step, methylmalonyl-CoA mutase acts on the R-methylmalonyl-CoA to produce succinyl-CoA.

SMP0121011

Pw122278 View Pathway
Physiological

Kidney Function - Collecting Duct

The collecting duct of the nephron is the last segment of the functioning nephron and is connected to minor calyces and the ensuing renal pelvis of the kidney where urine continues before it is stored in the bladder. The collecting duct is mainly responsible for the excretion and reabsorption of water and ions. It is composed of two important cell types: intercalated cells that are responsible for maintaining acid-base homeostasis, and principal cells that help maintain the body's water and salt balance. When renin is released from the kidneys, it causes the activation of angiotensin I in the blood circulation which is cleaved to become angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal cortex and release of vasopressin from the posterior pituitary gland. When in the circulation, vasopressin eventually binds to receptors on epithelial cells in the collecting ducts. This causes vesicles that contain aquaporins to fuse with the plasma membrane. Aquaporins are proteins that act as water channels once they have bound to the plasma membrane. As a result, the permeability of the collecting duct changes to allow for water reabsorption back into the blood circulation. In addition, sodium and potassium are also reabsorbed back into the systemic circulation at the collecting duct via potassium and sodium channels. However, aldosterone is a major regulator of the reabsorption of these ions as well, as it changes the permeability of the collective duct to these ions. As a result, a high concentration of sodium and potassium in the blood vessels occurs. Some urea and other ions may be reabsorbed as well. The reabsorption of ions and water increases blood fluid volume and blood pressure.

SMP0030880

Pw031778 View Pathway
Metabolic

Estrone Metabolism

Estrone (also known as oestrone) is a weak endogenous estrogen, a steroid and minor female sex hormone. Estrone is synthesized from cholesterol and secreted from gonads. Endoplasmic reticulum (ER) is the place that estrone undergoes primary metabolism. Estrone sulfate and estrone glucuronide are the conjugated product of estrone; and CYP450 can hydroxylate estrone into catechol estrogens. The enzyme catechol O-methyltransferase catalyzes the conversion of 2-hydroxyestrone into 2-methoxyestrone which is used to synthesize 2-methoxyestrone 3-glucuronide via the membrane-associated massive multimer UDP-glucuronosyltransferase 1-1. Estrone can also be reversibly converted into estradiol by estradiol 17-beta-dehydrogenase 1. This same enzyme can reversibly convert 16a-hydroxyestrone (synthesized from estrone via cytochrome P450 3A5) into estriol. Estriol is alternatively synthesized from estradiol via cytochrome P450 3A5.

SMP0000482

Pw000173 View Pathway
Metabolic

Mitochondrial Beta-Oxidation of Long Chain Saturated Fatty Acids

Fatty acids and their CoA byproducts can be found in many places in the body, playing major roles in many basic functions of the body. These include signalling roles, energy creation roles and enzyme regulation. Beta-oxidation is a process that occurs in the peroxisomes and in the mitochondria, although this pathway is focused on the mitochondrial piece of that process. Depending on the length of the fatty acid, beta-oxidation will either begin in the peroxisomes or the mitochondria. Very long chain fatty acids, fatty acids that consist of more than 22 carbons, can be reduced in the peroxisome where they become octanyl-CoA before moving to the mitochondria for the rest of the oxidation process. Stearoylcarnitine is transported by a mitochondrial carnitine/acylcarnitine carrier protein into the mitochondrial matrix, where it is converted to stearoyl-CoA through the enzyme carnitine o-palmitoyltransferase 2. Stearoyl-CoA then is catalyzed into (2E)-octadecenoyl-CoA by the enzyme long-chain specific acyl-CoA dehydrogenase. Then, enoyl-CoA hydratase converts (2E)-octadecenoyl-CoA into (s)-hydroxyoctadecanoyl-CoA. The pathway continues as hydroxyacyl-coenzyme A dehydrogenase cleaves (s)-hydroxyoctadecanoyl-CoA into 3-oxooctadecanoyl-CoA. 3-oxooctadecanoyl-CoA then uses 3-ketoacyl-CoA thiolase to create acetyl-CoA (necessary for the citric acid cycle) and uses trifunctional enzyme subunits alpha and beta to create palmityl-CoA. This palmityl-CoA is then converted by long-chain specific acyl-CoA dehydrogenase to (2E)-hexadecenoyl-CoA. Enoyl-CoA then converts (2E)-hexadecenoyl-CoA to 3-hydroxyhexadecanoyl-CoA, which is then turned into 3-oxohexadecanoyl-CoA by the enzyme hydroxyacyl-coenzyme A dehydrogenase. 3-ketoacyl-CoA thiolase then creates acetyl-CoA with the help of trifunctional enzyme subunits alpha and beta, which also produce tetradecanoyl-CoA from 3-oxohexadecanoyl-CoA. Long-chain specific acyl-CoA dehydrogenase then converts tetradecanoyl-CoA to (2E)-tetradecenoyl-CoA. (2E)-tetradecenoyl-CoA is then converted by the enzyme enoyl-CoA hydratase into 3-hydroxytetradecanoyl-CoA, which then creates 3-oxotetradecanoyl-CoA through the enzyme hydroxyacyl-coenzyme A dehydrogenase. Finally, the 3 enzymes 3-ketoacyl-coA thiolase, trifunctional enzyme subunit alpha and trifunctional enzyme subunit beta convert 3-oxotetradecanoyl-CoA into acetyl-CoA and lauroyl-CoA which can then be beta-oxidized as medium chain saturated fatty acids.

SMP0000020

Pw000010 View Pathway
Metabolic

Arginine and Proline Metabolism

The arginine and proline metabolism pathway illustrates the biosynthesis and metabolism of several amino acids including arginine, ornithine, proline, citrulline, and glutamate in mammals. In adult mammals, the synthesis of arginine takes place primarily through the intestinal-renal axis (PMID: 19030957). In particular, the amino acid citrulline is first synthesized from several other amino acids (glutamine, glutamate, and proline) in the mitochondria of the intestinal enterocytes (PMID: 9806879). The mitochondrial synthesis of citrulline starts with the deamination of glutamine to glutamate via mitochondrial glutaminase. The resulting mitochondrial glutamate is converted into 1-pyrroline-5-carboxylate via pyrroline-5-carboxylate synthase (P5CS). Alternately, the 1-pyrroline-5-carboxylate can be generated from mitochondrial proline via proline oxidase (PO). Ornithine aminotransferase (OAT) then converts the mitochondrial 1-pyrroline-5-carboxylate into ornithine and the enzyme ornithine carbamoyltransferase (OCT -- using carbamoyl phosphate) converts the ornithine to citrulline (PMID: 19030957). After this, the mitochondrial citrulline is released from the small intestine enterocytes and into the bloodstream where it is taken up by the kidneys for arginine production. Once the citrulline enters the kidney cells, the cytosolic enzyme argininosuccinate synthetase (ASS) will combine citrulline with aspartic acid to generate argininosuccinic acid. After this step, the enzyme argininosuccinate lyase (ASL) will remove fumarate from argininosuccinic acid to generate arginine. The resulting arginine can either stay in the cytosol where it is converted to ornithine via arginase I (resulting in the production of urea) or it can be transported into the mitochondria where it is decomposed into ornithine and urea via arginase II. The resulting mitochondrial ornithine can then be acted on by the enzyme ornithine amino transferase (OAT), which combines alpha-ketoglutarate with ornithine to produce glutamate and 1-pyrroline-5-carboxylate. The mitochondrial enzyme pyrroline-5-carboxylate dehydrogenase (P5CD) acts on the resulting 1-pyrroline-5-carboxylate (using NADPH as a cofactor) to generate glutamate. Alternately, the mitochondrial 1-pyrroline-5-carboxylate can be exported into the kidney cell’s cytosol where the enzyme pyrroline-5-carboxylate reductase (P5CR) can convert it to proline. While citrulline-to-arginine production primarily occurs in the kidney, citrulline is readily converted into arginine in other cell types, including adipocytes, endothelial cells, myocytes, macrophages, and neurons. Interestingly, chickens and cats cannot produce citrulline via glutamine/glutamate due to a lack of a functional pyrroline-5-carboxylate synthase (P5CS) in their enterocytes (PMID: 19030957).
Showing 101 - 110 of 48700 pathways