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Showing 71 - 80 of 49833 pathways
SMPDB ID Pathway Chemical Compounds Proteins


Pw000456 View Pathway

DNA Replication Fork

DNA is composed of two long and complementary strands, with a backbone on the outside and nucleotides in the middle. During replication the two strands of DNA separate; the resulting structure is called the replication fork. The replication fork forms because enzymes called helicases surround the DNA strands and break the hydrogen bonds which hold them together. The result is that two long branches, almost like fork prongs, each of which is a DNA strand. Replication of DNA has two main different processes. Because DNA is replicated in the 5' to 3' direction, and because both DNA strands in the replication fork are negative mirror images of each other, and because the replication fork is created on only one direction down the length of the DNA, two types of replication strands are formed: the leading and the lagging strand. These strands are so named by the way in which DNA polymerase reads the original DNA strand and attaches the complementary nucleotides as it makes its way along the chain. Because the direction of the movement of the replication fork, and the direction of the addition of nucleotides in the leading strand is the same, the process is continuous.That is, a polymerase is able to read the DNA and add the matching nucleotide bases to it continuously. In prokaryotes DNA polymerase III is responsible for creating the leading strand. The lagging strand is oriented in the opposite direction to the leading strand. Thus, replication of the lagging strand occurs in the opposing direction to that of the leading strand and the replication fork. As a result, replication of the lagging strand is a slower and more complicated process than that of the leading strand. Thus it is seen to lag behind the leading strand (hence the name).


Pw000564 View Pathway

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.


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.


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.


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.


Pw000038 View Pathway

Taurine and Hypotaurine Metabolism

There is an organic acid known as Taurine, which is a derivative product of sulfhydryl amino acid (which contains sulfur), as well as cysteine. The synthesis or metabolism in mammalian systems of this acid transpires within the pancreas in such a fashion that it utilizes a pathway known as the cysteine sulfinic acid pathway. To put this process in context, its occurrence is often seen in vivo, in hepatocytes, and is fundamental in the cyclical process of recovering bile acids from the intenstine, turning them back into salts and returning them to the bile. In essence the cysteine pathway induces a sulfhydryl group to be oxidized, creating cysteine sulfinic acid, by utilizing the appropriate enzymes (ie cysteine dioxygenase). This new acid undergoes decarboxylation creating a new compound: hypotaurine. This process goes on as Taurine now is subjected to conjugation vis a vis its amino terminal group. This includes acids such as chenodeoxycholic acid and cholic acid, and in turn the formation of bile salts occurs. Moreover, this entire process can be catalyzed via bile acid and a special amino acid N-acetyltransferase.


Pw000040 View Pathway

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.


Pw000021 View Pathway

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.


Pw000026 View Pathway

Glycerol Phosphate Shuttle

The glycerol phosphate shuttle also known as the glycerophosphate shuttle. It shuttles electrons to mitochondrial carriers in the oxidative phosphorylation pathway from cytosolic NADH. This shuttle relies on mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH). This is also a common process for the cell to regenerate cytosolic NAD+ for other processes.


Pw000153 View Pathway

Lactose Degradation

Lactose degradation (Lactose metabolism) shows the breakdown of alpha lactose into its constituent sugars, which are then utilized by the body as an energy source. Alpha-Lactose is the major sugar present in milk and the main source of energy supplied to the newborn mammalian in its mother’s milk. Lactose is also an important osmotic regulator of lactation. It is digested by the intestinal lactase, an enzyme expressed in newborns. Its activity declines following weaning. Lactase hydrolyzes alpha lactose into D-glucose and D-galactose, which are actively transported into the intestinal epithelial cells via the SGLT1 (GLUT1) cotransporter. GLUT1 actively transports glucose and galactose with 2 sodium ions. A sodium/potassium ATPase makes ATP by moving three sodium ions to the blood per two potassium ions that cross into the epithelial cell, giving the GLUT1 transporter energy to work. D-glucose and D-galactose diffuse into the blood, facilitated by the SLC2A2 transporter on the basolateral membrane on the intestinal epithelial cells. The sugars are then transported to liver.
Showing 71 - 80 of 49833 pathways