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Showing 81 - 90 of 49832 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0000449

Pw000021 View Pathway
Metabolic

Ethanol Degradation

Ethanol metabolism in humans occurs mainly in the liver, though degradation has also been shown in gastric, pancreatic, and lung tissue. Ethanol degradation occurs via four pathways, three of which are oxidative pathways and are depicted here. The fourth is a nonoxidative pathway which is less well studied but known to produce fatty acid ethyl esters. Each of the three oxidative pathways is differentiated by the mechanism utilized to oxidize ethanol to acetaldehyde in the first step. In the alcohol dehydrogenase mediated ethanol degradation pathway (I), cytoplasmic alcohol dehydrogenase produces the acetaldehyde from the ethanol. In the MEOS mediated ethanol degradation pathway (II), the ethanol enters the endoplasmic reticulum, where the Microsomal Ethanol Oxidising System (MEOS), also know as also known as cytochrome P-450 2E1, does the oxidizing and returns the acetaldehyde to the cytoplasm. In the catalase mediated ethanol degradation pathway (III), the oxidation occurs in the peroxisome via peroxisomal catalase, with the resulting acetaldehyde being released to the cytoplasm. In each of the three oxidative pathways the cytosolic acetaldehyde then enters the mitochondrial compartment, where it is converted to acetate by mitochondrial aldehyde dehydrogenase. The acetate leaves the mitochondria and moves to extra-hepatic tissues for further metabolism. In extra-hepatic cells the acetate is converted to acetyl-CoA via either cytoplasmic or mitochondrial acetyl-CoA synthetase. The alcohol dehydrogenase mediated ethanol degradation pathway (I) is the predominant mechanism of catabolism under conditions of acute alcohol consumption. However, under conditions of chronic ethanol consumption the MEOS mediated ethanol degradation pathway (II) and nonoxidative pathway are induced to assist with ethanol degradation.

SMP0000041

Pw000040 View Pathway
Metabolic

Sulfate/Sulfite Metabolism

This pathway illustrates the conversion of sulfite to sulfate (via sulfate oxidase) and subsequent generation of adenylylsulfate (APS) via 3'-phosphoadenosine 5'-phosphosulfate synthase 2. APS is converted to phosphoadenylyl-sulfate (PAPS) via adenylylsulfate kinase. APS can also be regenerated from PAPS by 3'(2'), 5'-bisphosphate nucleotidase 1. PAPS is eventually converted to adenosine bisophosphate (PAP) through the action of several different enzymes including aryl sulfotransferase, chondroitin 4-sulfotransferase 13 and estrone sulfotransferase. The metabolism pathway in question is important for many reasons. Recall, that the sulfite ion is in fact the conjugate base of sulfurous acid. Moreover, this ion is found naturally in one of the worlds most popular beverages, wines. Beyond its natural occurence, sulfite ion had the property of stopping fermentation. As such, the addition of it to products such as wine can be used either as a preservative or to stop the fermentation process at a moment which is of interest. Finally, this preservation property goes beyond merely wines, and finds utility in dried fruits, potatoes, etc.

SMP0000036

Pw000019 View Pathway
Metabolic

D-Arginine and D-Ornithine Metabolism

D-Amino acids have been show to be present in high concentrations in humans and play a role in biological functions. D-Amino may have negative effects as they can be found in some bacteria or form spontaneously in certain reactions. D-Amino acid oxidase (DAAO) is one of the main enzymes that metabolize D-Amino acids via deamination. DAAO is highly specific towards D-amino acids and favours free neutral D-amino acids or those with hydrophobic, polar or aromatic groups. Acidic amino acids are not catalyze by DAOO.

SMP0000024

Pw000158 View Pathway
Metabolic

Porphyrin Metabolism

This pathway depicts the synthesis and breakdown of porphyrin. The porphyrin ring is the framework for the heme molecule, the pigment in hemoglobin and red blood cells. The first reaction in porphyrin ring biosynthesis takes place in the mitochondria and involves the condensation of glycine and succinyl-CoA by delta-aminolevulinic acid synthase (ALAS). Delta-aminolevulinic acid (ALA) is also called 5-aminolevulinic acid. Following its synthesis, ALA is transported into the cytosol, where ALA dehydratase (also called porphobilinogen synthase) dimerizes 2 molecules of ALA to produce porphobilinogen. The next step in the pathway involves the condensation of 4 molecules of porphobilinogen to produce hydroxymethylbilane (also known as HMB). The enzyme that catalyzes this condensation is known as porphobilinogen deaminase (PBG deaminase). This enzyme is also called hydroxymethylbilane synthase or uroporphyrinogen I synthase. Hydroxymethylbilane (HMB) has two main fates. Most frequently it is enzymatically converted into uroporphyrinogen III, the next intermediate on the path to heme. This step is mediated by two enzymes: uroporphyrinogen synthase and uroporphyrinogen III cosynthase. Hydroxymethylbilane can also be non-enzymatically cyclized to form uroporphyrinogen I. In the cytosol, the uroporphyrinogens (uroporphyrinogen III or uroporphyrinogen I) are decarboxylated by the enzyme uroporphyrinogen decarboxylase. These new products have methyl groups in place of the original acetate groups and are known as coproporphyrinogens. Coproporphyrinogen III is the most important intermediate in heme synthesis. Coproporphyrinogen III is transported back from the cytosol into the interior of the mitochondria, where two propionate residues are decarboxylated (via coproporphyrinogen-III oxidase), which results in vinyl substituents on the 2 pyrrole rings. The resulting product is called protoporphyrinogen IX. The protoporphyrinogen IX is then converted into protoporphyrin IX by another enzyme called protoporphyrinogen IX oxidase. The final reaction in heme synthesis also takes place within the mitochondria and involves the insertion of the iron atom into the ring system generating the molecule known heme b. The enzyme catalyzing this reaction is known as ferrochelatase. The largest repository of heme in the body is in red blood cells (RBCs). RBCs have a life span of about 120 days. When the RBCs have reached the end of their useful lifespan, the cells are engulfed by macrophages and their constituents recycled or disposed of. Heme is broken down when the heme ring is opened by the enzyme known as heme oxygenase, which is found in the endoplasmic reticulum of the macrophages. The oxidation process produces the linear tetrapyrrole biliverdin, ferric iron (Fe3+), and carbon monoxide (CO). The carbon monoxide (which is toxic) is eventually discharged through the lungs. In the next reaction, a second methylene group (located between rings III and IV of the porphyrin ring) is reduced by the enzyme known as biliverdin reductase, producing bilirubin. Bilirubin is significantly less extensively conjugated than biliverdin. This reduction causes a change in the colour of the molecule from blue-green (biliverdin) to yellow-red (bilirubin). In hepatocytes, bilirubin-UDP-glucuronyltransferase (bilirubin-UGT) adds two additional glucuronic acid molecules to bilirubin to produce the more water-soluble version of the molecule known as bilirubin diglucuronide. In most individuals, intestinal bilirubin is acted on by the gut bacteria to produce the final porphyrin products, urobilinogens and stercobilins. These are excreted in the feces. The stercobilins oxidize to form brownish pigments which lead to the characteristic brown colour found in normal feces. Some of the urobilinogen produced by the gut bacteria is reabsorbed and re-enters the circulation. These urobilinogens are converted into urobilins that are then excreted in the urine which cause the yellowish colour in urine.

SMP0000029

Pw000007 View Pathway
Metabolic

Selenoamino Acid Metabolism

Phospholipids are membrane components in P. aeruginosa. The major phospholipids of P. aeruginosa are phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions. The reaction starts from a glycerone phosphate (dihydroxyacetone phosphate) produced in glycolysis. The glycerone phosphate is transformed into an sn-glycerol 3-phosphate (glycerol 3 phosphate) by NADPH-driven glycerol-3-phosphate dehydrogenase. sn-Glycerol 3-phosphate is transformed to a 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid). This can be achieved by an sn-glycerol-3-phosphate acyltransferase that interacts either with a long-chain acyl-CoA or with an acyl-[acp]. The 1-acyl-sn-glycerol 3-phosphate is transformed into a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) through a 1-acylglycerol-3-phosphate O-acyltransferase. This compound is then converted into a CPD-diacylglycerol through a CTP phosphatidate cytididyltransferase. CPD-diacylglycerol can be transformed either into an L-1-phosphatidylserine or an L-1-phosphatidylglycerol-phosphate through a phosphatidylserine synthase or a phosphatidylglycerophosphate synthase, respectively. The L-1-phosphatidylserine transforms into L-1-phosphatidylethanolamine through a phosphatidylserine decarboxylase. On the other hand, L-1-phosphatidylglycerol-phosphate gets transformed into an L-1-phosphatidyl-glycerol through a phosphatidylglycerophosphatase. These 2 products combine to produce a cardiolipin and an ethanolamine. The L-1 phosphatidyl-glycerol can also interact with cardiolipin synthase resulting in a glycerol and a cardiolipin.

SMP0000046

Pw000160 View Pathway
Metabolic

Pyrimidine Metabolism

A group of heterocyclic aromatic organic compound, pyrimidines are similar in structure to benzene and pyridine and count the nucleic acids cytosine, thymine, and uracil as structural derivatives. The following pathway illustrates a many pyrimidine-associated processes such as nucleotide biosynthesis, degradation, and salvage. This pathway depicts a number of pyrimidine-related processes such as nucleotide biosynthesis, degradation, and salvage. For pyrimidine nucleotide biosynthesis, carbamoyl phosphate derived from the action of carbamoyl phosphate synthetase II (CPS-II) on glutamine and bicarbonate is converted into carbamoyl aspartate by aspartate transcarbamoylase, ATCase. Dihydroorotic acid is subsequently generated by the action of carbamoyl aspartate dehydrogenase on carbamoyl aspartate. Dihydroorotate dehydrogenase then converts dihydroorotic acid to orotic acid. From this point, orotate phosphoribosyltransferase incorporates phosphoribosyl pyrophosphate into (PRPP) to produce orotidine monophosphate. Orotidine-5’-phosphate carboxylase subsequently converts orotidine monophosphate into uridine monophosphate (UMP). UMP is further phosphorylated twice to form UTP; the first instance by uridylate kinase and the second instance by ubiquitous nucleoside diphosphate kinase. UTP moves into the CTP synthesis pathway with the action of CTP synthase which aminates the molecule. The uridine nucleotides are also feedstock for the de novo thymine nucleotides synthesis pathway. DeoxyUMP which is derived from UDP or CDP metabolism is transformed by the action of thymidylate synthase into deoxyTMP of which the methyl group is sourced from N5,N10-methylene THF. THF is subsequently regenerated from DHF via dihydrofolate reductase (DHFR) which is essential for the continuation of thymidylate synthase activity. Serine hydroxymethyl transferase then acts on THF to regenerate N5,N10-THF. Pyrimidine synthesis is a comparatively simpler process than purine synthesis due to a couple of factors; pyrimidine ring structure is assembled as a free base rather being derived from PRPP and there is no branch in the pyrimidine synthesis pathway as opposed to the purine synthesis pathway. For thymidine, the action of thymidine kinase on it (or alternatively deoxyuridine) plays an important role in what is referred to as the salvage pathway to dTTP synthesis. However to form dTMP, the action of thymine phosphorylase and thymidine kinase is required. For deoxycytidine, deoxycytidine kinase is required (deoxycytidine also acts on deoxyadenosine and deoxyguanosine). For uracil, UMP can be formed by the action of uridine phosphorylase and uridine kinase on uracil. Pyrimidine catabolism ultimately results in the formation of the waste products of urea, H2O, and CO2. The product of cytosine breakdown, uracil, can be broken down to N-carbamoyl-β-alanine which can be catabolized into β-alanine. The product of thymine breakdown is β-aminoisobutyrate. The transamination of α-ketoglutarate to glutamate requires both of these breakdown products (β-alanine and β-aminoisobutyrate) to act as amine group donors. The products of this transamination can move through a further reaction that produces malonyl-CoA or methylmalonyl-CoA, a precursor for succinyl-CoA which is used in the Krebs cycle.

SMP0000588

Pw000564 View Pathway
Physiological

Striated Muscle Contraction

Tubular striated muscle cells (i.e. skeletal and cardiac myocytes) are composed of bundles of rod-like myofibrils. Each individual myofibril consists of many repeating units called sarcomeres. These functional units, in turn, are composed of many alternating actin and mysoin protein filaments that produce muscle contraction. The muscle contraction process is initiated when the muscle cell is depolarized enough for an action potential to occur. When acetylcholine is released from the motor neuron axon terminals that are adjacent to the muscle cells, it binds to receptors on the sarcolemma (muscle cell membrane), causing nicotinic acetylcholine receptors to be activated and the sodium/potassium channels to be opened. The fast influx of sodium and slow efflux of potassium through the channel causes depolarization. The resulting action potential that is generated travels along the sarcolemma and down the T-tubule, activating the L-type voltage-dependent calcium channels on the sarcolemma and ryanodine receptors on the sarcoplasmic reticulum. When these are activated, it triggers the release of calcium ions from the sarcoplasmic reticulum into the cytosol. From there, the calcium ions bind to the protein troponin which displaces the tropomysoin filaments from the binding sites on the actin filaments. This allows for myosin filaments to be able to bind to the actin. According to the Sliding Filament Theory, the myosin heads that have an ADP and phosphate attached binds to the actin, forming a cross-bridge. Once attached, the myosin performs a powerstroke which slides the actin filaments together. The ATP and phosphate are dislodged during this process. However, ATP now binds to the myosin head, which causes the myosin to detach from the actin. The cycle repeats once the attached ATP dissociates into ADP and phosphate, and the myosin performs another powerstroke, bringing the actin filaments even closer together. Numerous actin filaments being pulled together simultaneously across many muscles cells triggers muscle contraction.

SMP0121124

Pw122397 View Pathway
Metabolic

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.

SMP0121055

Pw122323 View Pathway
Metabolic

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.

SMP0000067

Pw000002 View Pathway
Metabolic

Aspartate Metabolism

Aspartate is synthesized by transamination of oxaloacetate by aspartate aminotransferase or amino acid oxidase. Aspartyl-tRNA synthetase can then couple aspartate to aspartyl tRNA for protein synthesis. The aspartate content in human proteins is about 7%. Asparagine synthase can convert aspartate to the polar amino acid asparagine. Aspartate is also a precursor for cellular signaling compounds such as, N-acetyl-aspartate, beta-alanine, adenylsuccinate, arginino-succinate and N-carbamoylaspartate. Aspartate is also a metabolite in the urea cycle and involved in gluconeogenesis. Additionally, aspartate carries the reducing equivalents in the mitochondrial malate-aspartate shuttle, which utilizes the ready interconversion of aspartate and oxaloacetate. The conjugate base of L-aspartic acid, aspartate, also acts as an excitatory neurotransmitter in the brain which activates NMDA receptors.
Showing 81 - 90 of 49832 pathways