Corydalis is a genus of about 470 species of annual and perennial herbaceous plants in the Papaveraceae family, native to the temperate Northern Hemisphere and the high mountains of tropical eastern Africa. They are most diverse in China and the Himalayas, with at least 357 species in China. Corydalis species are used as food plants by the larvae of some Lepidoptera species the clouded Apollo. Corydalis cava and some other tuberous species contain the alkaloid bulbocapnine, used in medicine but scientific evidence is lacking in the correct dosages and side effects. Many of the species in Corydalis contain other toxins and alkaloids like canadine, which blocks calcium. There are about 470 species, including: Photos of Corydalis species listed above Several former Corydalis have been moved to new genera: PseudofumariaCorydalis lutea = Pseudofumaria lutea Corydalis ochroleuca = Pseudofumaria albaCapnoidesCorydalis sempervirens = Capnoides sempervirens
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. They are sometimes called blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active site or to the allosteric site on a receptor, or they may interact at unique binding sites not involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding; the majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors. The English word antagonist in pharmaceutical terms comes from the Greek ἀνταγωνιστής – antagonistēs, "opponent, villain, rival", derived from anti- and agonizesthai.
Biochemical receptors are large protein molecules that can be activated by the binding of a ligand such as a hormone or a drug. Receptors can be membrane-bound, as cell surface receptors, or inside the cell as intracellular receptors, such as nuclear receptors including those of the mitochondrion. Binding occurs as a result of non-covalent interactions between the receptor and its ligand, at locations called the binding site on the receptor. A receptor may contain one or more binding sites for different ligands. Binding to the active site on the receptor regulates receptor activation directly; the activity of receptors can be regulated by the binding of a ligand to other sites on the receptor, as in allosteric binding sites. Antagonists mediate their effects through receptor interactions by preventing agonist-induced responses; this may be accomplished by binding to the allosteric site. In addition, antagonists may interact at unique binding sites not involved in the biological regulation of the receptor's activity to exert their effects.
The term antagonist was coined to describe different profiles of drug effects. The biochemical definition of a receptor antagonist was introduced by Ariens and Stephenson in the 1950s; the current accepted definition of receptor antagonist is based on the receptor occupancy model. It narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn "on" a single cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by'blocking' the receptor from the agonist; this definition remains in use for physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by alpha-adrenergic receptor activation.
Our understanding of the mechanism of drug-induced receptor activation and receptor theory and the biochemical definition of a receptor antagonist continues to evolve. The two-state model of receptor activation has given way to multistate models with intermediate conformational states; the discovery of functional selectivity and that ligand-specific receptor conformations occur and can affect interaction of receptors with different second messenger systems may mean that drugs can be designed to activate some of the downstream functions of a receptor but not others. This means efficacy may depend on where that receptor is expressed, altering the view that efficacy at a receptor is receptor-independent property of a drug. By definition, antagonists display no efficacy to activate the receptors they bind. Antagonists do not maintain the ability to activate a receptor. Once bound, antagonists inhibit the function of agonists, inverse agonists, partial agonists. In functional antagonist assays, a dose-response curve measures the effect of the ability of a range of concentrations of antagonists to reverse the activity of an agonist.
The potency of an antagonist is defined by its half maximal inhibitory concentration. This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist. Elucidating an IC50 value is useful for comparing the potency of drugs with similar efficacies, however the dose-response curves produced by both drug antagonists must be similar; the lower the IC50 the greater the potency of the antagonist, the lower the concentration of drug, required to inhibit the maximum biological response. Lower concentrations of drugs may be associated with fewer side-effects; the affinity of an antagonist for its binding site, i.e. its ability to bind to a receptor, will determine the duration of inhibition of agonist activity. The affinity of an antagonist can be determined experimentally using Schild regression or for competitive antagonists in radioligand binding studies using the Cheng-Prusoff equation. Schild regression can be used to determine the nature of antagonism as beginning either competitive or non-competitive and Ki determination is independent of the affinity, efficacy or concentration of the agonist used.
However, it is important. The effects of receptor desensitization on reaching equilibrium must als
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both inhibitory neurotransmission; the serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, epinephrine / norepinephrine, acetylcholine, as well as many hormones, including oxytocin, vasopressin, cortisol and substance P, among others; the serotonin receptors influence various biological and neurological processes such as aggression, appetite, learning, mood, nausea and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, anorectics, gastroprokinetic agents, antimigraine agents and entactogens. Serotonin receptors are found in all animals and are known to regulate longevity and behavioral aging in the primitive nematode, Caenorhabditis elegans.
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems. They can be divided into 7 families of G protein-coupled receptors except for the 5-HT3 receptor, a ligand-gated ion channel, which activate an intracellular second messenger cascade to produce an excitatory or inhibitory response. In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae, named pr5-HT8, it does not occur in mammals and shares low similarity to the known 5-HT receptor classes. The 7 general serotonin receptor classes include a total of 14 known serotonin receptors; the specific types have been characterized as follows: Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor. Nonselective agonists of 5-HT receptor subtypes include ergotamine, which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.
LSD is a 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist. The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. There is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from the embryonic period to the post-natal one. A number of receptors were classed as "5-HT1-like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant. Serotonin+Receptors at the US National Library of Medicine Medical Subject Headings "5-Hydroxytryptamine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Rubenstein LA, Lanzara RG. "Activation of G protein-coupled receptors entails cysteine modulation of agonist binding". Cogprints. Retrieved 2008-04-11. Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM.
"5-HT radioligands for human brain imaging with PET and SPECT". Med Res Rev. 33: 54–111. Doi:10.1002/med.20245. PMC 4188513. PMID 21674551
Tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group; the word "tyrosine" is from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional side chain. While tyrosine is classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine, it is encoded by the codons UAC and UAU in messenger RNA. Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality, it occurs in proteins. It functions as a receiver of phosphate groups. Phosphorylation of the hydroxyl group can change the activity of the target protein, or may form part of a signaling cascade via SH2 domain binding. A tyrosine residue plays an important role in photosynthesis. In chloroplasts, it acts as an electron donor in the reduction of oxidized chlorophyll.
In this process, it loses the hydrogen atom of its phenolic OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese clusters; the Dietary Reference Intake for phenylalanine and tyrosine is 33 mg per kilogram of body weight, or 15 mg per pound. For a 70 kg person, this is 2310 mg. Tyrosine, which can be synthesized in the body from phenylalanine, is found in many high-protein food products such as chicken, fish, yogurt, cottage cheese, peanuts, pumpkin seeds, sesame seeds, soy products, lima beans and bananas. For example, the white of an egg has about 250 mg per egg, while lean beef/lamb/pork/salmon/chicken/turkey contains about 1000 mg per 3 ounces portion. In plants and most microorganisms, tyr is produced via prephenate, an intermediate on the shikimate pathway. Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate, transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate.
Mammals synthesize tyrosine from the essential amino acid phenylalanine, derived from food. The conversion of phe to tyr is catalyzed by a monooxygenase; this enzyme catalyzes the reaction causing the addition of a hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine. Some of the tyrosine residues can be tagged with a phosphate group by protein kinases. In its phosphorylated form, tyrosine is called phosphotyrosine. Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase. Like the phosphotyrosine antibodies mentioned above, antibodies have been described that detect sulfotyrosine. In dopaminergic cells in the brain, tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase.
TH is the rate-limiting enzyme involved in the synthesis of the neurotransmitter dopamine. Dopamine can be converted into other catecholamines, such as norepinephrine and epinephrine; the thyroid hormones triiodothyronine and thyroxine in the colloid of the thyroid are derived from tyrosine. The latex of Papaver somniferum, the opium poppy, has been shown to convert tyrosine into the alkaloid morphine and the bio-synthetic pathway has been established from tyrosine to morphine by using Carbon-14 radio-labelled tyrosine to trace the in-vivo synthetic route. Tyrosine ammonia lyase is an enzyme in the natural phenols biosynthesis pathway, it transforms L-tyrosine into p-coumaric acid. Tyrosine is the precursor to the pigment melanin. Tyrosine is needed to synthesize the benzoquinone structure which forms part of coenzyme Q10; the decomposition of L-tyrosine begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate. The positional description para, abbreviated p, mean that the hydroxyl group and side chain on the phenyl ring are across from each other.
The next oxidation step catalyzes by p-hydroxyphenylpyruvate dioxygenase and splitting off CO2 homogentisate. In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentisate 1,2-dioxygenase is required. Thereby, through the incorporation of a further O2 molecule, maleylacetoacetate is created. Fumarylacetoacetate is created by maleylacetoacetate cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation; this cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is split by the enzyme fumarylacetoacetate hydrolase through the addition of a water molecule. Thereby fumarate and acetoacetate are liberated. Acetoacetate is a ketone body, activated with succinyl-CoA, thereafter it can be converted into acetyl-CoA, which in turn can be oxidized by the citric acid cycle or be used for fatty acid synthesis. Phloretic acid is a urinary metabolite of tyrosine in rats. Three structural isomers of L-tyrosine are known.
In addition to the common a
Alkaloids are a class of occurring organic compounds that contain basic nitrogen atoms. This group includes some related compounds with neutral and weakly acidic properties; some synthetic compounds of similar structure may be termed alkaloids. In addition to carbon and nitrogen, alkaloids may contain oxygen, sulfur and, more other elements such as chlorine and phosphorus. Alkaloids are produced by a large variety of organisms including bacteria, fungi and animals, they can be purified from crude extracts of these organisms by acid-base extraction. Alkaloids have a wide range of pharmacological activities including antimalarial, anticancer, vasodilatory, analgesic and antihyperglycemic activities. Many have found use as starting points for drug discovery. Other alkaloids possess psychotropic and stimulant activities, have been used in entheogenic rituals or as recreational drugs. Alkaloids can be toxic too. Although alkaloids act on a diversity of metabolic systems in humans and other animals, they uniformly evoke a bitter taste.
The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut. Compounds like amino acid peptides, nucleotides, nucleic acid and antibiotics are not called alkaloids. Natural compounds containing nitrogen in the exocyclic position are classified as amines rather than as alkaloids; some authors, consider alkaloids a special case of amines. The name "alkaloids" was introduced in 1819 by the German chemist Carl Friedrich Wilhelm Meißner, is derived from late Latin root alkali and the suffix -οειδής – "like". However, the term came into wide use only after the publication of a review article by Oscar Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s. There is no unique method of naming alkaloids. Many individual names are formed by adding the suffix "ine" to the genus name. For example, atropine is isolated from the plant Atropa belladonna. Where several alkaloids are extracted from one plant their names are distinguished by variations in the suffix: "idine", "anine", "aline", "inine" etc.
There are at least 86 alkaloids whose names contain the root "vin" because they are extracted from vinca plants such as Vinca rosea. Alkaloid-containing plants have been used by humans since ancient times for therapeutic and recreational purposes. For example, medicinal plants have been known in the Mesopotamia at least around 2000 BC; the Odyssey of Homer referred to a gift given to Helen by the Egyptian queen, a drug bringing oblivion. It is believed. A Chinese book on houseplants written in 1st–3rd centuries BC mentioned a medical use of Ephedra and opium poppies. Coca leaves have been used by South American Indians since ancient times. Extracts from plants containing toxic alkaloids, such as aconitine and tubocurarine, were used since antiquity for poisoning arrows. Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertürner isolated from opium a "soporific principle", which he called "morphium" in honor of Morpheus, the Greek god of dreams; the term "morphine", used in English and French, was given by the French physicist Joseph Louis Gay-Lussac.
A significant contribution to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelletier and Joseph Bienaimé Caventou, who discovered quinine and strychnine. Several other alkaloids were discovered around that time, including xanthine, caffeine, nicotine, colchicine and cocaine; the development of the chemistry of alkaloids was accelerated by the emergence of spectroscopic and chromatographic methods in the 20th century, so that by 2008 more than 12,000 alkaloids had been identified. The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg, he produced coniine by reacting 2-methylpyridine with acetaldehyde and reducing the resulting 2-propenyl pyridine with sodium. Compared with most other classes of natural compounds, alkaloids are characterized by a great structural diversity. There is no uniform classification; when knowledge of chemical structures was lacking, botanical classification of the source plants was relied on.
This classification is now considered obsolete. More recent classifications are based on similarity of the carbon biochemical precursor. However, they require compromises in borderline cases. Alkaloids are divided into the following major groups: "True alkaloids" contain nitrogen in the heterocycle and originate from amino acids, their characteristic examples are atropine and morphine. This group a
Phenylalanine is an essential α-amino acid with the formula C9H11NO2. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine; this essential amino acid is classified as neutral, nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins, coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine and epinephrine, the skin pigment melanin, it is encoded by the codons UUU and UUC. Phenylalanine is found in the breast milk of mammals, it is used in the manufacture of food and drink products and sold as a nutritional supplement for its reputed analgesic and antidepressant effects. It is a direct precursor to the neuromodulator phenethylamine, a used dietary supplement; as an essential amino acid, phenylalanine is not synthesized de novo in humans and other animals, who must ingest phenylalanine or phenylalanine-containing proteins.
The first description of phenylalanine was made in 1879, when Schulze and Barbieri identified a compound with the empirical formula, C9H11NO2, in yellow lupine seedlings. In 1882, Erlenmeyer and Lipp first synthesized phenylalanine from phenylacetaldehyde, hydrogen cyanide, ammonia; the genetic codon for phenylalanine was first discovered by J. Heinrich Matthaei and Marshall W. Nirenberg in 1961, they showed that by using mRNA to insert multiple uracil repeats into the genome of the bacterium E. coli, they could cause the bacterium to produce a polypeptide consisting of repeated phenylalanine amino acids. This discovery helped to establish the nature of the coding relationship that links information stored in genomic nucleic acid with protein expression in the living cell. Good sources of phenylalanine are eggs, liver, beef and soybeans; the Food and Nutrition Board of the U. S. Institute of Medicine set Recommended Dietary Allowances for essential amino acids in 2002. For phenylalanine plus tyrosine, for adults 19 years and older, 33 mg/kg body weight/day.
L-Phenylalanine is biologically converted into L-tyrosine, another one of the DNA-encoded amino acids. L-tyrosine in turn is converted into L-DOPA, further converted into dopamine and epinephrine; the latter three are known as the catecholamines. Phenylalanine uses the same active transport channel as tryptophan to cross the blood–brain barrier. In excessive quantities, supplementation can interfere with the production of serotonin and other aromatic amino acids as well as nitric oxide due to the overuse of the associated cofactors, iron or tetrahydrobiopterin; the corresponding enzymes in for those compounds are the aromatic amino acid hydroxylase family and nitric oxide synthase. Phenylalanine is the starting compound used in the synthesis of flavonoids. Lignan is derived from tyrosine. Phenylalanine is converted to cinnamic acid by the enzyme phenylalanine ammonia-lyase; the genetic disorder phenylketonuria is the inability to metabolize phenylalanine because of a lack of the enzyme phenylalanine hydroxylase.
Individuals with this disorder are known as "phenylketonurics" and must regulate their intake of phenylalanine. Phenylketonurics use blood tests to monitor the amount of phenylalanine in their blood. Lab results may report phenylalanine levels using either mg/dL and μmol/L. One mg/dL of phenylalanine is equivalent to 60 μmol/L. A "variant form" of phenylketonuria called hyperphenylalaninemia is caused by the inability to synthesize a cofactor called tetrahydrobiopterin, which can be supplemented. Pregnant women with hyperphenylalaninemia may show similar symptoms of the disorder, but these indicators will disappear at the end of gestation. Pregnant women with PKU must control their blood phenylalanine levels if the fetus is heterozygous for the defective gene because the fetus could be adversely affected due to hepatic immaturity. A non-food source of phenylalanine is the artificial sweetener aspartame; this compound is metabolized by the body into several chemical byproducts including phenylalanine.
The breakdown problems phenylketonurics have with the buildup of phenylalanine in the body occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in Australia, the U. S. and Canada that contain aspartame must be labeled: "Phenylketonurics: Contains phenylalanine." In the UK, foods containing aspartame must carry ingredient panels that refer to the presence of "aspartame or E951" and they must be labeled with a warning "Contains a source of phenylalanine." In Brazil, the label "Contém Fenilalanina" is mandatory in products which contain it. These warnings are placed to help individuals avoid such foods. Geneticists sequenced the genome of macaques in 2007, their investigations found "some instances where the normal form of the macaque protein looked like the diseased human protein" including markers for PKU. The stereoisomer D-phenylalanine can be produced by conventional organic synthesis, either as a single enantiomer or as a component of the racemic mixture.
It does not participate in protein biosynthesis although it is found in proteins in small amounts - aged proteins and food proteins that have been processed. The biological functions of D-amino acids remain unclear, although D-phenylalanine has pharmacological activity at niacin receptor 2. DL-Phenylalanine is marketed as a nutritional supplement for its purported analgesic and antidepressant activ