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Showing 91 - 100 of 49833 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0000068

Pw000045 View Pathway
Metabolic

Androgen and Estrogen Metabolism

This pathway describes the inactivation and catabolism of male (androgen) and female (estrogen) hormones. Many steroid hormones are transformed by sulfatases, dehydrogenases and glucuronide transferases to enhance their solubility and to facilitate their elimination. Inactivation means to convert an active compound into an inactive compound. Peripheral inactivation, which is inactivation caused by outside enzymes such as liver enzymes for example, is needed to maintain a steady-state level of plasma. This means that if either of these hormones are to be “chemical signals”, their half-life in the bloodstream has to be limited so that a variation in secretion rate can be emulated in the plasma. A large part of inactivation/catabolism occurs in the liver, although a little bit of catabolic activity does happen in the kidneys. Inactive androgens and estrogens are mostly eliminated in the urine. For this to happen, androgen and estrogen need to be converted to compounds that are less hydrophobic so that they are more soluble at higher concentrations. In this pathway, the conversion to a hydrophilic compound is an oxidation of a 17b-hydroxyl group. These hormones are needed for sexual development in both males and females.

SMP0000073

Pw000014 View Pathway
Metabolic

Butyrate Metabolism

Butyrate metabolism (Butanoate metabolism) describes the metabolic fate of a number of short chain fatty acids or short chain alcohols that are typically produced by intestinal fermentation. Many of these molecules are eventually used in the production of ketone bodies, the creation of short-chain lipids or as precursors to the citrate cycle, glycolysis or glutamate synthesis. The molecule for which this pathway is named, butyric acid, is a four-carbon fatty acid that is formed in the human colon by bacterial fermentation of carbohydrates (including dietary fiber). It is found in rancid butter, parmesan cheese, and vomit, and has an unpleasant odor and acrid taste, with a sweet aftertaste (similar to ether).

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.

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.

SMP0000040

Pw000146 View Pathway
Metabolic

Glycolysis

Glycolysis is a metabolic pathway with sequence of ten reactions involving ten intermediate compounds that converts glucose to pyruvate. Glycolysis release free energy for forming high energy compound such as ATP and NADH. Glycolysis is consisted of two phases, which one of them is chemical priming phase and second phase is energy-yielding phase. As the starting compound of chemical priming phase, D-glucose can be obtained from galactose metabolism or imported by monosaccharide-sensing protein 1 from outside of cell. D-Glucose is catalyzed by probable hexokinase-like 2 protein to form glucose 6-phosphate which is powered by ATP. Glucose 6-phosphate transformed to fructose 6-phosphate by glucose-6-phosphate isomerase, which the later compound will be converted to fructose 1,6-bisphosphate, which is the last reaction of chemical priming phase by 6-phosphofructokinase with cofactor magnesium, and it is also powered by ATP. Before entering the second phase, aldolase catalyzing the hydrolysis of F1,6BP into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Dihydroxyacetone phosphate and glyceraldehyde 3-phosphate can convert to each other bidirectionally by facilitation of triosephosphate isomerase. The second phase of glycolysis is yielding-energy phase that produce ATP and NADH. At the first step, D-glyceraldehyde 3-phosphate is catalyzed to glyceric acid 1,3-biphosphate by glyceraldehyde-3-phosphate dehydrogenase with NAD, which also generate NADH. ATP is generated through the reaction that convert glyceric acid 1,3-biphosphate to 3-phosphoglyceric acid. Phosphoglycerate mutase 2 catalyze 3-phosphoglyceric acid to 2-Phospho-D-glyceric acid, and alpha-enolase with cofactor magnesium catalyzes 2-Phospho-D-glyceric acid to phosphoenolpyruvic acid. Eventually, plastidial pyruvate kinase 4 converts phosphoenolpyruvic acid to pyruvate with cofactor magnesium and potassium and ADP. Pyruvate will undergo pyruvate metabolism, tyrosine metabolism and pantothenate and CoA biosynthesis.

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.

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.

SMP0121018

Pw122285 View Pathway
Physiological

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.

SMP0000715

Pw000692 View Pathway
Metabolic

Methylhistidine Metabolism

Methylhistidine is a modified amino acid that is produced in myocytes during the methylation of actin and myosin. It is also formed from the methylation of L-histidine, which takes the methyl group from S-adenosylmethionine and forms S-adenosylhomocysteine as a byproduct. After its formation in the myocytes, methylhistidine enters the blood stream and travels to the kidneys, where it is excreted in the urine. Methylhistidine is present in the blood and urine in higher concentrations after skeletal muscle protein breakdown, which can occur due to disease or injury. Because of this, it can be used to judge how much muscle breakdown is occurring. Methylhistidine levels are also affected by diet, and may differ between vegetarian diets and those containing meats.
Showing 91 - 100 of 49833 pathways