An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa.
A class of organic compounds known as STEROLS or STEROIDS derived from plants.
Sterol Regulatory Element Binding Protein 1
A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.
Sterol Regulatory Element Binding Protein 2
A sterol regulatory element binding protein that regulates GENES involved in CHOLESTEROL synthesis and uptake.
A triterpene that derives from the chair-boat-chair-boat folding of 2,3-oxidosqualene. It is metabolized to CHOLESTEROL and CUCURBITACINS.
An intermediate in the synthesis of cholesterol.
Sterol Regulatory Element Binding Proteins
Sterol regulatory element binding proteins are basic helix-loop-helix leucine zipper transcription factors that bind the sterol regulatory element TCACNCCAC. They are synthesized as precursors that are threaded into the MEMBRANES of the ENDOPLASMIC RETICULUM.
Hydroxymethylglutaryl CoA Reductases
Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.
A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.
An autosomal recessive lipid storage disorder due to mutation of the gene CYP27A1 encoding a CHOLESTANETRIOL 26-MONOOXYGENASE. It is characterized by large deposits of CHOLESTEROL and CHOLESTANOL in various tissues resulting in xanthomatous swelling of tendons, early CATARACT, and progressive neurological symptoms.
An autosomal recessive disorder of CHOLESTEROL metabolism. It is caused by a deficiency of 7-dehydrocholesterol reductase, the enzyme that converts 7-dehydrocholesterol to cholesterol, leading to an abnormally low plasma cholesterol. This syndrome is characterized by multiple CONGENITAL ABNORMALITIES, growth deficiency, and INTELLECTUAL DISABILITY.
Bile Acids and Salts
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.
A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
The first committed enzyme of the biosynthesis pathway that leads to the production of STEROLS. it catalyzes the synthesis of SQUALENE from farnesyl pyrophosphate via the intermediate PRESQUALENE PYROPHOSPHATE. This enzyme is also a critical branch point enzyme in the biosynthesis of ISOPRENOIDS that is thought to regulate the flux of isoprene intermediates through the sterol pathway.
A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)
A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.
Chromatography, Thin Layer
Oxidoreductases Acting on CH-CH Group Donors
The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes.
A complex of polyene antibiotics obtained from Streptomyces filipinensis. Filipin III alters membrane function by interfering with membrane sterols, inhibits mitochondrial respiration, and is proposed as an antifungal agent. Filipins I, II, and IV are less important.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
ATP-Binding Cassette Transporters
Substances used to lower plasma CHOLESTEROL levels.
Lipid Metabolism, Inborn Errors
Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.
Cytochrome P-450 Enzyme System
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Gas Chromatography-Mass Spectrometry
Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.
Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.
14-alpha Demethylase Inhibitors
Cholesterol substituted in any position by a keto moiety. The 7-keto isomer inhibits 3-hydroxy-3-methylglutaryl-CoA reductase activity and inhibits cholesterol uptake in the coronary arteries and aorta in vitro.
Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex are nystatin A1, A2, and A3.
Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.
A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.