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Showing 21 - 30 of 48701 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0121128

Pw122406 View Pathway
Physiological

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.

SMP0000059

Pw000162 View Pathway
Metabolic

Urea Cycle

Urea, also known as carbamide, is a waste product made by a large variety of living organisms and is the main component of urine. Urea is created in the liver, through a string of reactions that are called the Urea Cycle. This cycle is also called the Ornithine Cycle, as well as the Krebs-Henseleit Cycle. There are some essential compounds required for the completion of this cycle, such as arginine, citrulline and ornithine. Arginine cleaves and creates urea and ornithine, and the reactions that follow see urea residue build up on ornithine, which recreates arginine and keeps the cycle going. Ornithine is transported to the mitochondrial matrix, and once there, ornithine carbamoyltransferase uses carbamoyl phosphate to create citrulline. After this, citrulline is transported to the cytosol. Once here, citrulline and aspartate team up to create argininosuccinic acid. After this, argininosuccinate lyase creates l-arginine. L-arginine finally uses arginase-1 to create ornithine again, which will be transported to the mitochondrial matrix and restart the urea cycle once more.

SMP0014212

Pw015076 View Pathway
Metabolic

Phosphatidylcholine Biosynthesis

Phosphatidylcholines (PC) are a class of phospholipids that incorporate a phosphocholine headgroup into a diacylglycerol backbone. They are the most abundant phospholipid in eukaryotic cell membranes and has both structural and signalling roles. In eukaryotes, there exist two phosphatidylcholine biosynthesis pathways: the Kennedy pathway and the methylation pathway. The Kennedy pathway begins with the direct phosphorylation of free choline into phosphocholine followed by conversion into CDP-choline and subsequently phosphatidylcholine. It is the major synthesis route in animals. The methylation pathway involves the 3 successive methylations of phosphatidylethanolamine to form phosphatidylcholine. The first reaction of the Kennedy pathway involves the cytosol-localized enzyme choline/ethanolamine kinase catalyzing the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. A parallel Kennedy pathway forms phosphatidylethanolamine from ethanolamine - the only difference being a different enzyme, ethanolamine-phosphate cytidylyltransferase, catalyzing the second step. Phosphatidylethanolamine is also synthesized from phosphatidylserine in the mitochondrial membrane by phosphatidylserine decarboxylase. Phosphatidylethanolamine funnels into the methylation pathway in which phosphatidylethanolamine N-methyltransferase (PEMT) then catalyzes three sequential N-methylation steps to convert phosphatidylethanolamine to phosphatidylcholine. PEMT uses S-adenosyl-L-methionine as a methyl donor.

SMP0000031

Pw000055 View Pathway
Metabolic

Pentose Phosphate Pathway

The pentose phosphate pathway—also referred to in the literature as the phosphogluconate pathway, the hexose monophosphate shunt, or the pentose phosphate shunt—is involved in the generation of NADPH as well as pentose sugars. Of the total cytoplasmic NADPH used in biosynthetic reactions, a significant proportion of it is generated through the pentose phosphate pathway. Ribose 5-phosphate is also another essential product generated by this pathway which is employed in nucleotide synthesis. The pentose phosphate pathway is also involved in the digestive process as the products of nucleic acid catabolism can be metabolized through the pathway (pentose sugars are usually yielded in the breakdown) while the carbon backbones of dietary carbohydrates can be converted into glycolytic/gluconeogenic intermediates. The pentose phosphate pathway is interconnected to the glycolysis pathway through the shared use of three intermediates: glucose 6-phosphate, glyceraldehyde 3-phosphate, and fructose 6-phosphate. The pathway can be described as eight distinct reactions (see below) and is separated into an oxidative phase and a non-oxidative phase. Reactions 1-3 form the oxidative phase and generate NADPH and pentose 5-phosphate. Reactions 4-8 form the non-oxidative phase and converts pentose 5-phosphate into other pentose sugars such as ribose 5-phosphate, but generates no NADPH. The eight reactions are as follows: reaction 1 where glucose-6-phosphate 1-dehydrogenase converts glucose 6-phosphate into D-glucono-1,5-lactone 6-phosphate with NADPH formation; reaction 2 where 6-phosphogluconolactonase converts D-glucono-1,5-lactone 6-phosphate into 6-phospho-D-gluconate;reaction 3 where 6-phosophogluconate dehydrogenase converts 6-phospho-D-gluconate into ribulose 5-phosphate with NADPH formation; reaction 4 where ribulose-phosphate 3-epimerase converts ribulose 5-phosphate into xylulose 5-phosphate; reaction 5 where ribose-5-phosphate isomerase converts ribulose 5-phosphate into ribose 5-phosphate; reaction 6 where transketolase rearranges ribose 5-phosphate and xylulose 5-phosphate to form sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate; reaction 7 where transaldolase rearranges of sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate; and reaction 8 where transkelotase rearranges of xylulose 5-phosphate and erythrose 4-phosphate to form glyceraldehyde 3-phosphate and fructose-6-phosphate.

SMP0090879

Pw091899 View Pathway
Physiological

Hop Pathway in Cardiac Development

The transcription of DNA is aided in large part by something called "homeodomain transcription factors". They are a diverse group of DNA binding factors. In fact, genes which are created with the aid of homeodomain factors tend to conglomerate and are responsible for anterior-posterior patterning. There is much to be said as well regarding the development and growth of cardiac myocytes and homedomain transcription factors. Indeed, at the early stages of the cell differentiation of cardiac myoctes a delicate balance of joint expression of several factors is needed for correct development (namely: serum response factor (SRF), and GATA4) and a homeodomain factor known as Nkx2-5! The joint expression of the aforementioned factors is the critical in the development of myocytes as well as gene expression in the cardiac region. To underline the importance of the homeodomain transcription factors, note that an error in the Nkx2-5 gene has severe consequences, which include, though are not necessarily limited to, embryonic lethality, as well as severe problems in general heart development. To put all this in context of the pathway in question, Hop actually stands for (Homeodomain Only Protein). The Hop gene plays an important role in the cardiac development we have been describing, as it too encodes a homedomain factor which plays an important role at the onset stages of cardiac development. The Hop gene is downstream of the Mkx2-5 factor we discussed earlier, and similar to it, improper activation of Hop can lead to severe cardiac development issues. In mice for example, not have the Hop gene results in alterations to the cell cycle. In particular, cardiac cells are unable to exit the cycle at the correct stage and continue grow after normal developmental stage has finished. There exists an interesting symbiosis between Hop and SRF. First, Hop regulates gene expression by either binding to SRF or by preventing SRF binding to DNA. This occurs because Hop does not have anything to bind to DNA with, and as such must have different methods to regulate gene expression. Second, when Hop blocks normal SRF binding, the results is that the activation of genes in the heart is affected and normal development does not occur. In a nutshell, what can be said about this tango action of SRF and Hop is this: during the first stages of development, what is observed is that the Hop interaction is one which results in a cessation of the differentiation processes which are induced by SRF. In the later stages, it appears that Hop reduces cell proliferation which is normally caused by SRF.

SMP0000053

Pw000024 View Pathway
Metabolic

Folate Metabolism

Folate, or folic acid, is a very important B-vitamin involved in cell creation and preservation, as well as the protection of DNA from mutations that can cause cancer. It is commonly found in leafy green vegetables, but is also present in many other foods such as fruit, dairy products, eggs and meat. Folate is imperative during pregnancy as a deficiency will cause neural tube defects in the offspring. Many countries around the world now fortify foods with folic acid to prevent such defects. This pathway begins in the extracellular space, where folic acid is transported into the cell through a proton-coupled folate transporter. From there, dihydrofolate reductase converts folic acid into dihydrofolic acid. Dihydrofolic acid is then created into tetrahydrofolic acid through dihydrofolate reductase. Tetrahydrofolic acid then sparks the beginning of many reactions and subpathways including purine metabolism and histidine metabolism. There are two reactions that tetrahydrofolic acid undergoes, the first being the catalyzation into tetrahydrofolyl-[glu](2) through the enzyme folylpolyglutamate synthase in the mitochondria. Then, tetrahydrofolyl-[glu](2) becomes tetrahydrofolyl-[glu](n) through folylpolyglutamate synthase. The cycle ends with tetrahydrofolyl-[glu](n) reverting to tetrahydrofolyl-[glu](2) in the lysosome through the enzyme gamma-glutamyl hydrolase. The second reaction that begins with tetrahydrofolic acid sees tetrahydrofolic acid turned into 10-formyltetrahydrofolate through c-1-tetrahydrofolate synthase. This loop is completed by cytosolic 10-formyltetrahydrofolate dehydrogenase reverting 10-formyltetrahydrofolate back to tetrahydrofolic acid. Folate is not stored in the body for very long, as it is a water soluble vitamin and is excreted through urine, so it is important to ingest it continually, as your body’s level of folate will decline after a few weeks if the vitamin is avoided.

SMP0000076

Pw000036 View Pathway
Metabolic

Thiamine Metabolism

Thiamine, (Vitamin B1), is a compound found in many different foods such as beans, seafood, meats and yogurt. It is usually maintained by the consumption of whole grains. It is an essential part of energy metabolism. This means that thiamine helps convert carbohydrates into energy. Eating carbohydrates increases the need for this vitamin, as your body can only store about 30mg at a time due to the vitamins short half-life. Thiamine was first synthesized in 1936, which was very helpful in researching its properties in relation to beriberi, a vitamin b1 deficiency. This deficiency has been observed mainly in countries where rice is the staple food. Thiamine metabolism begins in the extracellular space, being transported by a thiamine transporter into the cell. Once in the intracellular space, thiamine is converted into thiamine pyrophosphate through the enzyme thiamin pyrophosphate kinase 1. Thiamine pyrophosphate is then converted into thiamine triphosphate, again using the enzyme thiamin pyrophosphatekinase 1. After this, thiamine triphosphate uses thiamine-triphosphatase to revert to thiamine pyrophosphate, which undergoes a reaction using cancer-related nuceloside-triphosphatase to become thiamine monophosphate. This phosphorylated form is a metabolically active form of thiamine, as are the two other compounds, derivatives of thiamine, mentioned previously. The enzymes used in this pathway both stem from the upper small intestine. Thiamine is passed mainly through urine. It is a water-soluble vitamin, which means it dissolves in water and is carried to different parts of the body but is not stored in the body.

SMP0000025

Pw000048 View Pathway
Metabolic

Phospholipid Biosynthesis

This pathway describes the synthesis of the common phospholipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and cardiolipins. Phospholipid synthesis is mediated by two possible mechanisms: (1) A CDP-activated polar head group for attaches to the phosphate of phosphatidic acid or (2) A CDP-activated 1,2-diacylglycerol and an inactivated polar head group. The ER membrane is the primary site of phospholipid synthesis using precursors imported into the ER from the cytosol. To initiate the process, phosphatidic acid is generated by the linkage of two fatty acids associated with coenzyme A (CoA) carriers to glycerol-3-phosphate. This new molecule is inserted into the membrane where a phosphatase converts it into diacylglycerol or alternatively it is formed into phosphatidylinositol before the conversion. If the conversion into diacylglycerol occurs, the molecule has three possible fates depending on the type of polar head group attached: phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine. At their inception, a phospholipid is composed of a saturated fatty acid and unsaturated fatty acid on the C1 and C2 carbon of the glycerol backbone respectively. With the continuous remodelling of the phospholipid bilayer, this fatty acid distribution at these carbons changes. For example, acyl group remodelling changes the presence of acyl groups on the glycerol backbone (which were initially placed there by acyl transferases) and moves it further into the membrane as a consequence of the action of phospholipase A1 (PLA1) and phospholipase A2 (PLA2). Another modifying group that is usually added are alcohol-containing groups such as serine, ethanol amine, and choline which contain positively-charged nitrogen.

SMP0000037

Pw000029 View Pathway
Metabolic

Lysine Degradation

The degradation of L-lysine happens in liver and it is consisted of seven reactions. L-Lysine is imported into liver through low affinity cationic amino acid transporter 2 (cationic amino acid transporter 2/SLC7A2). Afterwards, L-lysine is imported into mitochondria via mitochondrial ornithine transporter 2. L-Lysine can also be obtained from biotin metabolism. L-Lysine and oxoglutaric acid will be combined to form saccharopine by facilitation of mitochondrial alpha-aminoadipic semialdehyde synthase, and then, mitochondrial alpha-aminoadipic semialdehyde synthase will further breaks saccharopine down to allysine and glutamic acid. Allysine will be degraded to form aminoadipic acid through alpha-aminoadipic semialdehyde dehydrogenase. Oxoadipic acid is formed from catalyzation of mitochondrial kynurenine/alpha-aminoadipate aminotransferase on aminoadipic acid. Oxoadipic acid will be further catalyzed to form glutaryl-CoA, and glutaryl-CoA converts to crotonoyl-CoA, and crotonoyl-CoA transformed to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA will form Acetyl-CoA as the final product through the intermediate compound: acetoacetyl-CoA. Acetyl-CoA will undergo citric acid cycle metabolism. Carnitine is another key byproduct of lysine metabolism (not shown in this pathway).

SMP0000044

Pw000043 View Pathway
Metabolic

Histidine Metabolism

Histidine, an amino acid, plays an important role in the creation of proteins. It is unique as an amino acid as it is needed for nucleotide formation. The biosynthesis of histidine in adults begins with the condensation of ATP and PRPP (phosphoribosyl pyrophosphate) to form n-5-phosphoribosyl 1-pyrophosphate (phosphoribosyl-ATP). It is also worth noting that PRPP is the beginning compound for purine and pyrimidine creation. Subsequent histidine biosynthetic steps (from phosphoribosyl-ATP onwards) are likely to occur in the intestinal microflora. Elimination of the phosphate and the opening of the ring in phosphoribosyl-ATP forms phosphoribosyl-forminino-5-aminoimidazole-4-carboxamide ribonucleotide(phosphoribosyl-forminino-AICAR-phosphate). This is subsequently converted to 5-phosphoribulosyl-forminino-5-aminoimidazole-4-carboxamide ribonucleotide. Cleavage of this compound creates imidazole glycerol phosphate and AICAR (aminoimidazolecarboxamide ribonucleotide) with glutamine being involved as an amino group donor. AICAR is used again through the purine pathway while the imidazole glycerol phosphate is converted to imidazole acetal phosphate. Transamination yields histidinol phosphate which is then turned into histidinol, and then, finally, to histidine. L-histidine is catalyzed by histidine ammonia-lyase into urocanic acid. This acid is then converted to 4-imidazolone-5-propionic acid by urocanate hydratase. 4-imidazolone-5-propionic acid is then converted to formiminoglutamic acid, using the enzyme probable imidazolonepropionase. One last reaction occurs to allow for glutamate metabolism, as formiminoglutamic acid is converted to l-glutamic acid through the use of formimidoyltransferase-cyclodeaminase. Histidine is also a precursor for carnosine biosynthesis(via carnosine synthase), with beta-alanine being the rate limiting precursor. Anserine can be synthesized either from carnosine via carnosine N-methyltransferase or from 1-methylhistidine via carnosine synthase. Inversely, cytosolic non-specific dipeptidase catalyzes the synthesis of 1-methylhistidine from anserine. Histidine is found in meat, seeds, nuts and whole grains. It is a very important amino acid in keeping a pH of 7 in the body, as it acts as a shuttle for protons to maintain a balance of acids and bases in the blood and different tissues.
Showing 21 - 30 of 48701 pathways