Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.Geranyltranstransferase: An enzyme involved in the MEVALONATE pathway, it catalyses the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate.Polyisoprenyl Phosphates: Phosphoric or pyrophosphoric acid esters of polyisoprenoids.Heme Oxygenase (Decyclizing): A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. EC 1.14.99.3.Heme Oxygenase-1: A ubiquitous stress-responsive enzyme that catalyzes the oxidative cleavage of HEME to yield IRON; CARBON MONOXIDE; and BILIVERDIN.Dimethylallyltranstransferase: An enzyme that, in the pathway of cholesterol biosynthesis, catalyzes the condensation of isopentenyl pyrophosphate and dimethylallylpyrophosphate to yield pyrophosphate and geranylpyrophosphate. The enzyme then catalyzes the condensation of the latter compound with another molecule of isopentenyl pyrophosphate to yield pyrophosphate and farnesylpyrophosphate. EC 2.5.1.1.Farnesol: A colorless liquid extracted from oils of plants such as citronella, neroli, cyclamen, and tuberose. It is an intermediate step in the biological synthesis of cholesterol from mevalonic acid in vertebrates. It has a delicate odor and is used in perfumery. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)SesquiterpenesTransferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2.Hemiterpenes: The five-carbon building blocks of TERPENES that derive from MEVALONIC ACID or deoxyxylulose phosphate.Mevalonic AcidFarnesyl-Diphosphate Farnesyltransferase: 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.Hemeproteins: Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)Prenylation: Attachment of isoprenoids (TERPENES) to other compounds, especially PROTEINS and FLAVONOIDS.Carbon-Carbon Lyases: Enzymes that catalyze the cleavage of a carbon-carbon bond by means other than hydrolysis or oxidation. This subclass contains the DECARBOXYLASES, the ALDEHYDE-LYASES, and the OXO-ACID-LYASES. EC 4.1.Protoporphyrins: Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.Carbon Monoxide: Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Terpenes: A class of compounds composed of repeating 5-carbon units of HEMITERPENES.Organophosphorus Compounds: Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.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.Lovastatin: 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.SqualeneAmino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Diterpenes: Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.Geranylgeranyl-Diphosphate Geranylgeranyltransferase: An enzyme that catalyzes the condensation of two molecules of geranylgeranyl diphosphate to give prephytoene diphosphate. The prephytoene diphosphate molecule is a precursor for CAROTENOIDS and other tetraterpenes.Kinetics: The rate dynamics in chemical or physical systems.Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group.Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Diphosphonates: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.Sesquiterpenes, Germacrane: SESQUITERPENES cyclized to one 10-carbon ring.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Spectrum Analysis, Raman: Analysis of the intensity of Raman scattering of monochromatic light as a function of frequency of the scattered light.Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.Piperidines: A family of hexahydropyridines.Carbon-Carbon Double Bond Isomerases: Enzymes that catalyze the shifting of a carbon-carbon double bond from one position to another within the same molecule. EC 5.3.3.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Tricarboxylic Acids: Organic compounds that are acyclic and contain three acid groups. A member of this class is citric acid which is the first product formed by reaction of pyruvate and oxaloacetate. (From Lehninger, Principles of Biochemistry, 1982, p443)Ferrochelatase: A mitochondrial enzyme found in a wide variety of cells and tissues. It is the final enzyme in the 8-enzyme biosynthetic pathway of HEME. Ferrochelatase catalyzes ferrous insertion into protoporphyrin IX to form protoheme or heme. Deficiency in this enzyme results in ERYTHROPOIETIC PROTOPORPHYRIA.Heptanoates: Salts and esters of the 7-carbon saturated monocarboxylic acid heptanoic acid.Metalloporphyrins: Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds.Diphosphates: Inorganic salts of phosphoric acid that contain two phosphate groups.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Proto-Oncogene Proteins p21(ras): Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)Dolichol: Eicosamethyl octacontanonadecasen-1-o1. Polyprenol found in animal tissues that contains about 20 isoprene residues, the one carrying the alcohol group being saturated.Hydroxymethylglutaryl-CoA Synthase: An enzyme that catalyzes the synthesis of hydroxymethylglutaryl-CoA from acetyl-CoA and acetoacetyl-CoA. This is a key enzyme in steroid biosynthesis. This enzyme was formerly listed as EC 4.1.3.5.Salicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.Progeria: An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.Artemisia: A plant genus of the family ASTERACEAE with strong-smelling foliage. It is a source of SANTONIN and other cytotoxic TERPENES.HemopexinHemoglobins: The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.Aminolevulinic Acid: A compound produced from succinyl-CoA and GLYCINE as an intermediate in heme synthesis. It is used as a PHOTOCHEMOTHERAPY for actinic KERATOSIS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Micrococcus luteus: A species of gram-positive, spherical bacteria whose organisms occur in tetrads and in irregular clusters of tetrads. The primary habitat is mammalian skin.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cytochrome b Group: Cytochromes (electron-transporting proteins) with protoheme (HEME B) as the prosthetic group.Mentha: Mentha is a genus of the mint family (LAMIACEAE). It is known for species having characteristic flavor and aroma.Cytochromes: Hemeproteins whose characteristic mode of action involves transfer of reducing equivalents which are associated with a reversible change in oxidation state of the prosthetic group. Formally, this redox change involves a single-electron, reversible equilibrium between the Fe(II) and Fe(III) states of the central iron atom (From Enzyme Nomenclature, 1992, p539). The various cytochrome subclasses are organized by the type of HEME and by the wavelength range of their reduced alpha-absorption bands.Whales: Large marine mammals of the order CETACEA. In the past, they were commercially valued for whale oil, for their flesh as human food and in ANIMAL FEED and FERTILIZERS, and for baleen. Today, there is a moratorium on most commercial whaling, as all species are either listed as endangered or threatened.Nitrogen Compounds: Inorganic compounds that contain nitrogen as an integral part of the molecule.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Hydroxymethylglutaryl-CoA Reductase Inhibitors: Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Electron Transport Complex IV: A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane.Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (LATEX) of HEVEA brasiliensis and other trees and plants. It is a substance that can be stretched at room temperature to at least twice its original length and after releasing the stress, retract rapidly, and recover its original dimensions fully.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Bacterial Proteins: Proteins found in any species of bacterium.Oxidoreductases: 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)Centella: A plant of the family APIACEAE which is the source of asiatic acid and asiaticoside. Centella asiatica (L.) Urb. = Hydrocotyle asiatica L. is known for effect on peripheral circulation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Oncogene Protein p21(ras): Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.Histidine: An essential amino acid that is required for the production of HISTAMINE.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Cyclization: Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Simvastatin: A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.Hevea: A plant genus of the family EUPHORBIACEAE, order Euphorbiales, subclass Rosidae. Commercial natural RUBBER is mainly obtained from Hevea brasiliensis but also from some other plants.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Apoproteins: The protein components of a number of complexes, such as enzymes (APOENZYMES), ferritin (APOFERRITINS), or lipoproteins (APOLIPOPROTEINS).Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Deuteroporphyrins: Porphyrins with four methyl and two propionic acid side chains attached to the pyrrole rings.Porphobilinogen Synthase: An enzyme that catalyzes the formation of porphobilinogen from two molecules of 5-aminolevulinic acid. EC 4.2.1.24.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Pentanes: Five-carbon saturated hydrocarbon group of the methane series. Include isomers and derivatives.Sterols: Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)Dolichol Phosphates: Phosphoric acid esters of dolichol.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Drug Antagonism: Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy.Levulinic Acids: Keto acids that are derivatives of 4-oxopentanoic acids (levulinic acid).Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Oxygen: An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.PeroxidasesEnzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Etidronic Acid: A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Protein Methyltransferases: Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.Artemisia annua: A plant species of the genus ARTEMISIA, family ASTERACEAE. It is the source of the antimalarial artemisinin (ANTIMALARIALS).Monoterpenes: Compounds with a core of 10 carbons generally formed via the mevalonate pathway from the combination of 3,3-dimethylallyl pyrophosphate and isopentenyl pyrophosphate. They are cyclized and oxidized in a variety of ways. Due to the low molecular weight many of them exist in the form of essential oils (OILS, VOLATILE).Metmyoglobin: Myoglobin which is in the oxidized ferric or hemin form. The oxidation causes a change in color from red to brown.Bilirubin: A bile pigment that is a degradation product of HEME.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Mesoporphyrins: Porphyrins with four methyl, two ethyl, and two propionic acid side chains attached to the pyrrole rings.Monomeric GTP-Binding Proteins: A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 3.6.1.47Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Sodium Benzoate: The sodium salt of BENZOIC ACID. It is used as an antifungal preservative in pharmaceutical preparations and foods. It may also be used as a test for liver function.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Electron Transport: The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent: Specific hydroxymethylglutaryl CoA reductases that utilize the cofactor NAD. In liver enzymes of this class are involved in cholesterol biosynthesis.Intramolecular Lyases: Enzymes of the isomerase class that catalyze reactions in which a group can be regarded as eliminated from one part of a molecule, leaving a double bond, while remaining covalently attached to the molecule. (From Enzyme Nomenclature, 1992) EC 5.5.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.Cyanides: Inorganic salts of HYDROGEN CYANIDE containing the -CN radical. The concept also includes isocyanides. It is distinguished from NITRILES, which denotes organic compounds containing the -CN radical.Cytochrome-c Peroxidase: A hemeprotein which catalyzes the oxidation of ferrocytochrome c to ferricytochrome c in the presence of hydrogen peroxide. EC 1.11.1.5.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Tetrapyrroles: Four PYRROLES joined by one-carbon units linking position 2 of one to position 5 of the next. The conjugated bond system results in PIGMENTATION.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Ferric Compounds: Inorganic or organic compounds containing trivalent iron.Biosynthetic Pathways: Sets of enzymatic reactions occurring in organisms and that form biochemicals by making new covalent bonds.Benzodiazepines: A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.Porphyrias: A diverse group of metabolic diseases characterized by errors in the biosynthetic pathway of HEME in the LIVER, the BONE MARROW, or both. They are classified by the deficiency of specific enzymes, the tissue site of enzyme defect, or the clinical features that include neurological (acute) or cutaneous (skin lesions). Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Bicyclo Compounds, Heterocyclic: A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)Naphthols: Naphthalene derivatives carrying one or more hydroxyl (-OH) groups at any ring position. They are often used in dyes and pigments, as antioxidants for rubber, fats, and oils, as insecticides, in pharmaceuticals, and in numerous other applications.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Lamin Type A: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.Ferrous Compounds: Inorganic or organic compounds that contain divalent iron.Horses: Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest.Receptors, Epoprostenol: Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.
  • Furthermore, inactivation of Ras by farnesyl transferase inhibitor or K-Ras small interfering RNA attenuated NO-induced increase in proliferation signaling and cyclin D1 and ODC translation, further confirming the involvement of Ras activation during NO-induced cell proliferation. (aacrjournals.org)
  • Although increasing evidence suggests that exchange of intermediates occurs between these compartments, the cytoplasmic mevalonate pathway is generally considered to supply the precursors for the production of sesquiterpenes and triterpenes (including sterols) and to provide precursors for protein prenylation and for ubiquinone and heme-A production in mitochondria. (schoolbag.info)
  • Statins block production of Farnesyl PPi by blocking HMG CoA reductase in the synthesis of lipid pathway. (epomedicine.com)
  • Farnesol (FOH) is an isoprenoid alcohol that may be endogenously generated within the cells by enzymatic dephosphorylation of farnesyl pyrophosphate (FPP), an intermediate of the metabolic pathway yielding sterols and other isoprenoid compounds from mevalonate ( 4 ). (asm.org)
  • Biochemical analyses in various Cercospora species provide evidence that these fungi synthesize ABA directly from farnesyl diphosphate, via different oxidative steps, with either 1′-4′-dihydroxy-γ-ionylidene acetate, 1′-deoxy-ABA, or 1′-4′-trans-diol ABA as intermediates, and not via the carotenoid pathway used by higher plants ( 1 , 20 - 22 ). (asm.org)
  • As may be seen in the figure, the left shows representations of electron-density clouds of the de-oxygenated heme group, depicted in pink, and the attached histidine residue which may be seen in light blue . (wikibooks.org)
  • How might an electron be "transported" the 20 � distance from the dinuclear CuA cluster to the Fe in heme a and ultimately on to dioxygen? (libretexts.org)
  • Another consequence of electron transfer to heme a involves the interaction of S382 and the farnesyl OH group, which are close in space and proximal to a water cavity. (libretexts.org)
  • From photosynthetic pigments to plant defense compounds, from flavor compounds in cinnamon, mint, ginger and cloves to plant and animal hormones, from the cannabinoids in marijuana to the lycopene that gives tomatoes their color, and from heme to the quinones in the electron transport chain, isoprenoids are ubiquitous in cells. (libretexts.org)
  • The transfer of the farnesyl tune to the C2 chocolate group is catalyzed by the discussion identified as heme A: The equilibrium checking for the dissociation of joining inhibitor complexes is known as Ki: Merck in-licensed L-threo-isoleucyl thiazolidide and its allo rock. (usagiftsshops.com)
  • The backbone carbonyl group between 440 and 441 forms an "indirect" interaction with R38 which we showed earlier is affected by the redox state of heme a. (libretexts.org)
  • In the Chlorobiaceae species, the C-cyt cz consists of an N-terminal transmembrane domain and a C-terminal soluble domain that binds the single heme group. (springer.com)
  • What would be the consequence if dioxygen, a substrate for the reaction, dissociated from the heme a3 Fe before it were completely reduced? (libretexts.org)
  • This nonplanar configuration is characteristic of the deoxygenated heme group, and is often referred to as being "domed shape" . (wikibooks.org)
  • Both the formyl and hydroxyethylfarnesyl groups of heme A are thought to play important roles in this critical process, as published by the influential group of S. Yoshikawa. (wikipedia.org)
  • 13. The method of claim 1, wherein said at least one terpene is selected from the group consisting of a taxadiene, a linalool, a valencene, a phytoene, an amorpha-4,11-diene, a limonene and a farnesyl diphosphate. (patentsencyclopedia.com)
  • Heme D is another form of heme B. Instead, the hydroxylated propionic acid side chain forms a gamma-spirolactone. (wikibooks.org)
  • The correct structure of heme A, based upon NMR and IR experiments of the reduced, Fe(II), form of the heme, was published in 1975. (wikipedia.org)