Genes altered in major depressive disorder
Genes altered in major depressive disorder
Positive relationships between CYP19A1 and other components at different levels (count: 0)
Positive relationship network of CYP19A1 in MK4MDD
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1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
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Negative relationships between CYP19A1 and MDD (count: 0)
Negative relationships between CYP19A1 and other components at different levels (count: 0)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Steroid hormones derived from cholesterol are a class of bio......
Steroid hormones derived from cholesterol are a class of biologically active compounds in vertebrates. The cholesterol side-chain cleavage enzyme CYP11A1 catalyzes conversion of cholesterol, a C27 compound, to the first C21 steroid, pregnenolone, which is converted by a bifunctional enzyme complex to the gestagen hormone, progesterone. Pregnenolone and progesterone are the starting materials for the three groups of steroids: C21 steroids of glucocorticoids and mineralocorticoids, C19 steroids of androgens, and C18 steroids of estrogens. (i) Progesterone is converted by hydroxylations at carbons 21 and 11 to corticosterone, which is further modified by hydroxylation and oxydoreduction at carbon 18 to yield aldosterone, a mineralcorticoid. Cortisol, the main glucocorticoid, is formed from 17alpha-hydroxyprogesterone with 11-deoxycortisol as an intermediate. (ii) Male hormone testosterone is formed from pregnenolone by two pathways, delta5 pathway via dehydroepiandrosterone and delta4 pathway via androstenedione. The enzyme CYP17A1 is responsible for the 17,20 lyase and 17alpha-hydroxylase activities in respective pathways. (iii) Female hormones estrone and estradiol are formed from testosterone and 4-androstene-3,17-dione by oxidative removal of the C19 methyl group and subsequent aromatization of ring A. In addition to these three groups, recent studies show that there is another group, termed neurosteroids, synthesized in the brain rather than the peripheral endocrine gland.More...
Phase 1 of metabolism is concerned with functionalization, t......
Phase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conjugating species with which to react with. Many xenobiotics are lipophilic and almost chemically inert (e.g. PAHs) so would not necessarily undergo a phase 2 reaction. Making them more chemically reactive would facilitate their excretion but also increases their chance of reacting with cellular macromolecules (e.g. proteins, DNA). There is a fine balance between producing a more reactive metabolite and conjugation reactions. There are two groups of enzymes in phase 1 - oxidoreductases and hydrolases. Oxidoreductases introduce an oxygen atom into or remove electrons from their substrates. The major oxidoreductase enzyme system is called the P450 monooxygenases. Other systems include flavin-containing monooxygenases (FMO), cyclooxygenases (COX) and monoamine oxidases (MAO). Hydrolases hydrolyse esters, amides, epoxides and glucuronides.More...
A number of CYPs take part in cholesterol biosynthesis and e......
A number of CYPs take part in cholesterol biosynthesis and elimination, thus playing an important role in maintaining cholesterol homeostasis. Under normal physiological conditions, cholesterol intake (diet or synthesized de novo from acetyl CoA) equals cholesterol elimination (degraded to bile salts, secreted in bile and used in steroid hormone synthesis). These processes are under tight regulatory control and any disruption leads to increased cholesterol levels resulting in cardiovacular disease. The CYPs involved in cholesterol homeostasis could serve as potential targets for cholesterol-lowering drugs.More...
Steroid hormones are synthesized primarily in the adrenal gl......
Steroid hormones are synthesized primarily in the adrenal gland and gonads. They regulate energy metabolism and stress responses (glucocorticoids), salt balance (mineralocorticoids), and sexual development and function (androgens and estrogens). All steroids are synthesized from cholesterol. Steroid hormone synthesis is largely regulated at the initial steps of cholesterol mobilization and transport into the mitochondrial matrix for conversion to pregnenolone. In the body, the fate of pregnenolone is tissue-specific: in the zona fasciculata of the adrenal cortex it is converted to cortisol, in the zona glomerulosa to aldosterone, and in the gonads to testosterone and then to estrone and estradiol. These pathways are outlined in the figure below, which also diagrams the sites on the cholesterol molecule that undergo modification in the course of these reactions.More...
Lipids are hydrophobic but otherwise chemically diverse mole......
Lipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphingolipids, eicosanoids, cholesterol, bile salts, steroid hormones, and fat-soluble vitamins, and function as a major source of energy (fatty acids, triacylglycerols, and ketone bodies), are major constituents of cell membranes (cholesterol and phospholipids), play a major role in their own digestion and uptake (bile salts), and participate in numerous signaling and regulatory processes (steroid hormones, eicosanoids, and sphingolipids). Because of their poor solubility in water, most lipids in extracellular spaces in the human body are found as complexes with specific carrier proteins. Regulation of the formation and movement of these lipoprotein complexes is a critical aspect of human lipid metabolism, and lipoprotein abnormalities are associated with major human disease processes including atherosclerosis and diabetes. Aspects of lipid metabolism currently annotated in Reactome include lipid digestion, trafficking of dietary sterols, triacylglycerol synthesis (fatty acid synthesis and triacylglycerol assembly), hormone-sensitive lipase-mediated triacylglycerol breakdown, and beta-oxidation of fatty acids, ketone body metabolism (synthesis and utilization), the synthesis of cholesterol, bile salts, and steroid hormones, and sphingolipid metabolism. Three aspects of lipoprotein function are currently annotated: chylomicron-mediated lipid transport, HDL (high density lipoprotein)-mediated lipid transport, and LDL (low density lipoprotein) endocytosis and degradation.More...
Active steroid hormones are produced from the precursor chol......
Active steroid hormones are produced from the precursor cholesterol.The steps involved in the biosynthesis of the adrenal steroid hormones, corticosterone, cortisol, and aldosterone; and the gonadal steroid hormones, progesterone, estradiol, and testosterone are annotated here. The enzymes that catalyze these reactions fall into two major classes of proteins: the cytochrome P450 heme-containing proteins and the hydroxysteroid dehydrogenases.More...
Hormones are chemicals released in very small quantities by ......
Hormones are chemicals released in very small quantities by cells that affect cellular metabolism in other parts of the body. They can also act as chemical messengers that transport signals from one cell to another. All multicellular organisms produce hormones; these are often transported in the blood. Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses. The events annotated here describe the biosynthesis of many types of hormones.More...
Steroids are a class of lipids characterized by the structur......
Steroids are a class of lipids characterized by the structure of four fused rings shown in the figure below. The central steroid in human biology is cholesterol, obtained from animal fats consumed in the diet or synthesized de novo from acetyl-coenzyme A. (Vegetable fats contain various sterols but no cholesterol.) Cholesterol is an essential constituent of lipid bilayer membranes and is the starting point for the biosyntheses of bile acids and salts, steroid hormones, and vitamin D. Bile acids and salts, e.g., taurocholate, are mostly synthesized in the liver. They are released into the intestine and function as detergents to solubilize dietary fats. Steroid hormones are mostly synthesized in the adrenal gland and gonads. They regulate energy metabolism and stress responses (glucocorticoids such as cortisol), salt balance (mineralocorticoids such as aldosterone), and sexual development and function (androgens and estrogens such as estradiol). At the same time, chronically elevated cholesterol levels in the body are associated with the formation of atherosclerotic lesions and hence increased risk of heart attacks and strokes. Pathways of steroid metabolism annotated in Reactome are cholesterol biosynthesis, the synthesis and recycling of bile acids and salts, and the synthesis of steroid hormones. The human body lacks a mechanism for degrading excess cholesterol, although an appreciable amount is lost daily in the form of bile salts and acids that escape recycling.More...
All organisms are constantly exposed to foreign chemicals ev......
All organisms are constantly exposed to foreign chemicals every day. These can be man-made. Once chemicals undergo functionalization, the electrophilic or nucleophilic species can be detrimental to biological systems. Electrophiles can react with electron-rich macromolecules such as proteins, DNA and RNA by covalent interaction whilst nucleophiles have the potential to interact with biological receptors. That's why conjugation is so important as it mops up these potentially reactive species. Many chemicals, when exposed to certain metabolizing enzymes can induce those enzymes, a process called enzyme induction. The effect of this is that these chemicals accelerate their own biotransformation and excretion. The reverse is also true where some chemicals cause enzyme inhibition. Some other factors that alter enzyme levels are sex, age and genetic predisposition. Between species, there can be considerable differences in biotransformation ability which is a problem faced by drug researchers interpreting toxicological results to humans.More...
The P450 isozyme system is the major phase 1 biotransforming......
The P450 isozyme system is the major phase 1 biotransforming system in man, accounting for more than 90% of drug biotransformations. This system has huge catalytic versatility and a broad substrate specificity, acting upon xenobiotica and endogenous compounds. It is also called the mixed-function oxidase system, the P450 monooxygenases and the heme-thiolate protein system. All P450 enzymes are a group of heme-containing isozymes which are located on the membrane of the smooth endoplasmic reticulum. They can be found in all tissues of the human body but are most concentrated in the liver. The name cytochrome P450. CYPs are grouped into 14 families according to their sequence similarity. Generally, enzymes in the same family share 40% sequence similarity and 55% within a subfamily. Nomenclature of P450s is as follows. CYP (to represent cytochrome P450 superfamily), followed by an arabic number for the family, a capital letter for the subfamily and finally a second arabic number to denote the isoenzyme. An example is CYP1A1 which is the first enzyme in subfamily A of cytochrome P450 family 1. The majority of the enzymes are present in the CYP1-4 families. CYP1-3 are primarily concerned with xenobiotic biotransformation whereas the other CYPs deal primarily with endogenous compounds. The CYP section is structured by the typical substrate they act upon. Of the 57 human CYPs, 7 encode mitochondrial enzymes, all involved in sterol biosynthesis. Of the remaining 50 microsomal enzymes, 20 act upon endogenous compounds, 15 on xenobiotics and 15 are the so-called orphan enzymes with no substrate identified. The P450 catalytic cycle (picture) shows the steps involved when a substrate binds to the enzyme. (1) The normal state of a P450 with the iron in its ferric state. (2) The substrate binds to the enzyme. (3) The enzyme is reduced to the ferrous state by the addition of an electron from NADPH cytochrome P450 reductase. The bound substrate facilitates this process. (4,5) Molecular oxygen binds and forms an Fe2+OOH complex with the addition of a proton and a second donation of an electron from either NADPH cytochrome P450 reductase or cytochrome b5. A second proton cleaves the Fe2+OOH complex to form water. (6) An unstable 3+ complex donates its oxygen to the substrate (7). The oxidised substrate is released and the enzyme returns to its initial state (1).More...
CYP19A1 related interactors from protein-protein interaction data in HPRD (count: 1)
Basic Information
Positive relationships between CYP19A1 and other components at different levels (count: 0)
