Bilins, bilanes or bile pigments are biological pigments formed in many organisms as a metabolic product of certain porphyrins. Bilin was named as a bile pigment of mammals, but can be found in lower vertebrates, invertebrates, as well as red algae, green plants and cyanobacteria. Bilins can range in color from red, yellow or brown to blue or green. In chemical terms, bilins are linear arrangements of four pyrrole rings. In human metabolism, bilirubin is a breakdown product of heme. A modified bilane is an intermediate in the biosynthesis and uroporphyrinogen III from porphobilinogen. Examples of bilins are found in animals, phycocyanobilin, the chromophore of the photosynthetic pigment phycocyanin in algae and plants. In plants, bilins serve as the photopigments of the photoreceptor protein phytochrome. An example of an invertebrate bilin is micromatabilin, responsible for the green color of the Green Huntsman Spider, Micrommata virescens. Bilirubin Biliverdin Phycobilin Phycobiliprotein Phycoerythrobilin Stercobilin Urobilin Gmelin's test Bilin at the US National Library of Medicine Medical Subject Headings
Heme or haem is a coordination complex "consisting of an iron ion coordinated to a porphyrin acting as a tetradentate ligand, to one or two axial ligands." The definition is loose, many depictions omit the axial ligands. Many porphyrin-containing metalloproteins have heme as their prosthetic group. Hemes are most recognized as components of hemoglobin, the red pigment in blood, but are found in a number of other biologically important hemoproteins such as myoglobin, catalases, heme peroxidase, endothelial nitric oxide synthase; the word heme is derived from Greek αἷμα haima meaning blood. Hemoproteins have diverse biological functions including the transportation of diatomic gases, chemical catalysis, diatomic gas detection, electron transfer; the heme iron serves as a source or sink of electrons during electron redox chemistry. In peroxidase reactions, the porphyrin molecule serves as an electron source. In the transportation or detection of diatomic gases, the gas binds to the heme iron. During the detection of diatomic gases, the binding of the gas ligand to the heme iron induces conformational changes in the surrounding protein.
In general, diatomic gases only bind to the reduced heme, as ferrous Fe while most peroxidases cycle between Fe and Fe and hemeproteins involved in mitochondrial redox, oxidation-reduction, cycle between Fe and Fe. It has been speculated that the original evolutionary function of hemoproteins was electron transfer in primitive sulfur-based photosynthesis pathways in ancestral cyanobacteria-like organisms before the appearance of molecular oxygen. Hemoproteins achieve their remarkable functional diversity by modifying the environment of the heme macrocycle within the protein matrix. For example, the ability of hemoglobin to deliver oxygen to tissues is due to specific amino acid residues located near the heme molecule. Hemoglobin reversibly binds to oxygen in the lungs when the pH is high, the carbon dioxide concentration is low; when the situation is reversed, hemoglobin will release oxygen into the tissues. This phenomenon, which states that hemoglobin's oxygen binding affinity is inversely proportional to both acidity and concentration of carbon dioxide, is known as the Bohr effect.
The molecular mechanism behind this effect is the steric organization of the globin chain. There are several biologically important kinds of heme: The most common type is heme B. Isolated hemes are designated by capital letters while hemes bound to proteins are designated by lower case letters. Cytochrome a refers to the heme A in specific combination with membrane protein forming a portion of cytochrome c oxidase; the following carbon numbering system of porphyrins is an older numbering used by biochemists and not the 1–24 numbering system recommended by IUPAC, shown in the table above. Heme l is the derivative of heme B, covalently attached to the protein of lactoperoxidase, eosinophil peroxidase, thyroid peroxidase; the addition of peroxide with the glutamyl-375 and aspartyl-225 of lactoperoxidase forms ester bonds between these amino acid residues and the heme 1- and 5-methyl groups, respectively. Similar ester bonds with these two methyl groups are thought to form in eosinophil and thyroid peroxidases.
Heme l is one important characteristic of animal peroxidases. Lactoperoxidase and eosinophil peroxidase are protective enzymes responsible for the destruction of invading bacteria and virus. Thyroid peroxidase is the enzyme catalyzing the biosynthesis of the important thyroid hormones; because lactoperoxidase destroys invading organisms in the lungs and excrement, it is thought to be an important protective enzyme. Heme m is the derivative of heme B covalently bound at the active site of peroxide. Heme m contains the two ester bonds at the heme 1- and 5-methyls as in heme l found in other mammalian peroxides. In addition, a unique sulfonamide ion linkage between the sulfur of a methionyl amino-acid residue and the heme 2-vinyl group is formed, giving this enzyme the unique capability of oxidizing chloride and bromide ions. Myeloperoxidase is present in mammalian neutrophils and is responsible for the destruction of invading bacteria and viruses, it synthesizes hypobromite by "mistake", a known mutagenic compound.
Heme D is another derivative of heme B, but in which the propionic acid side chain at the carbon of position 6, hydroxylated, forms a γ-spirolactone. Ring III is hydroxylated at position 5, in a conformation trans to the new lactone group. Heme D is the site for oxygen reduction to water of many types of bacteria at low oxygen tension. Heme S is related to heme B by having a formal group at position 2 in place of the 2-vinyl group. Heme S is found in the hemoglobin of marine worms; the correct structures of heme B and heme S were first elucidated by German chemist Hans Fischer. The names of cytochromes reflect the kinds of hemes they contain: cytochrome a contains heme A, cytochrome c contains heme C, etc; this convention may have been first introduced with the publication of the structure of heme A. The practice of designating hemes with upper case letters was formalized in a footnote in a paper by Puustinen and Wikstrom which explains under which conditions a capital letter should be used: "we prefer the use of capital letters to describe the heme structure as isolated.
Lowercase letters may then
Phytochromes are a class of photoreceptor in plants and fungi use to detect light. They are sensitive to light in the red and far-red region of the visible spectrum and can be classed as either Type I, which are activated by far-red light, or Type II that are activated by red light. Recent advances have suggested that phytochromes act as temperature sensors, as warmer temperatures enhance their de-activation. Phytochromes control many aspects of plant development, they regulate the germination of seeds, the synthesis of chlorophyll, the elongation of seedlings, the size and number and movement of leaves and the timing of flowering in adult plants. Phytochromes are expressed across many tissues and developmental stages. Other plant photoreceptors include cryptochromes and phototropins, which respond to blue and ultraviolet-A light and UVR8, sensitive to ultraviolet-B light. Phytochromes consist of a protein, covalently linked to a bilin chromophore; the protein part comprises two identical chains.
Each chain has GAF domain and PHY domain. Domain arrangements in plant and fungal phytochromes are comparable insofar, as the three N-terminal domains are always PAS, GAF and PHY domains; however C-terminal domains are more divergent. The PAS domain serves as a signal sensor and the GAF domain is responsible for binding to cGMP and senses light signals. Together, these subunits form the phytochrome region, which regulates physiological changes in plants to changes in red and far red light conditions. In plants, red light changes phytochrome to its biologically active form, while far red light changes the protein to its biologically inactive form. Phytochromes are characterised by a red/far-red photochromicity. Photochromic pigments change their "colour" upon light absorption. In the case of phytochrome the ground state is Pr, the r indicating that it absorbs red light strongly; the absorbance maximum is a sharp peak 650–670 nm, so concentrated phytochrome solutions look turquoise-blue to the human eye.
But once a red photon has been absorbed, the pigment undergoes a rapid conformational change to form the Pfr state. Here fr indicates that now far-red is preferentially absorbed; this shift in absorbance is apparent to the human eye as a more greenish colour. When Pfr absorbs far-red light it is converted back to Pr. Hence, red light makes Pfr, far-red light makes Pr. In plants at least Pfr is the "signalling" state. Chemically, phytochrome consists of a chromophore, a single bilin molecule consisting of an open chain of four pyrrole rings, covalently bonded to the protein moiety via conserved cysteine amino acid, it is the chromophore that absorbs light, as a result changes the conformation of bilin and subsequently that of the attached protein, changing it from one state or isoform to the other. The phytochrome chromophore is phytochromobilin, is related to phycocyanobilin and to the bile pigment bilirubin; the term "bili" in all these names refers to bile. Bilins are derived from the closed tetrapyrrole ring of haem by an oxidative reaction catalysed by haem oxygenase to yield their characteristic open chain.
Chlorophyll too is derived from haem. In contrast to bilins and chlorophyll carry a metal atom in the center of the ring, iron or magnesium, respectively; the Pfr state passes on a signal to other biological systems in the cell, such as the mechanisms responsible for gene expression. Although this mechanism is certainly a biochemical process, it is still the subject of much debate, it is known that although phytochromes are synthesized in the cytosol and the Pr form is localized there, the Pfr form, when generated by light illumination, is translocated to the cell nucleus. This implies a role of phytochrome in controlling gene expression, many genes are known to be regulated by phytochrome, but the exact mechanism has still to be discovered, it has been proposed that phytochrome, in the Pfr form, may act as a kinase, it has been demonstrated that phytochrome in the Pfr form can interact directly with transcription factors. The phytochrome pigment was discovered by Sterling Hendricks and Harry Borthwick at the USDA-ARS Beltsville Agricultural Research Center in Maryland during a period from the late 1940s to the early 1960s.
Using a spectrograph built from borrowed and war-surplus parts, they discovered that red light was effective for promoting germination or triggering flowering responses. The red light responses were reversible by far-red light, indicating the presence of a photoreversible pigment; the phytochrome pigment was identified using a spectrophotometer in 1959 by biophysicist Warren Butler and biochemist Harold Siegelman. Butler was responsible for the name, phytochrome. In 1983 the laboratories of Peter Quail and Clark Lagarias reported the chemical purification of the intact phytochrome molecule, in 1985 the first phytochrome gene sequence was published by Howard Hershey and Peter Quail. By 1989, molecular genetics and work with monoclonal antibodies that more than one type of phytochrome existed, it is now known by genome sequencing that Arabidopsis has five phytochrome genes but that rice has only three. While this represents the conditio
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
Protochlorophyllide, or monovinyl protochlorophyllide, is an immediate precursor of chlorophyll a that lacks the phytol side-chain of chlorophyll. Protochlorophyllide is fluorescent. In angiosperms, the last step, conversion of protochlorophyllide to chlorophyll, is light-dependent, such plants are pale if grown in the darkness. Gymnosperms and photosynthetic bacteria have another, light-independent enzyme and grow green in the darkness as well; the enzyme that converts protochlorophyllide to chlorophyllide is protochlorophyllide reductase, EC 188.8.131.52. There are two structurally unrelated proteins with this activity: the light-dependent and the dark-operative; the light-dependent reductase needs light to operate. The dark-operative version is a different protein, consisting of three subunits that exhibit significant sequence similarity to the three subunits of nitrogenase, which catalyzes the formation of ammonia from dinitrogen; this enzyme might be evolutionary older but is sensitive to free oxygen and does not work if its concentration exceeds about 3%.
Hence, the alternative, light-dependent version needed to evolve. Most of the photosynthetic bacteria have both light-independent reductases. Angiosperms have lost the dark-operative form and rely on 3 different copies of light-dependent version abbreviated as POR A, B, C. Gymnosperms have much more copies of the similar gene. In plants, POR is encoded in the cell nucleus and only transported to its place of work, chloroplast. Unlike with POR, in plants and algae that have the dark-operative enzyme it is at least encoded in the chloroplast genome. Chlorophyll itself is bound to proteins and can transfer the absorbed energy in the required direction. Protochlorophyllide, occurs in the free form and, under light conditions, acts as a photosensitizer, forming toxic free radicals. Hence, plants need an efficient mechanism of regulating the amount of chlorophyll precursor. In angiosperms, this is done at the step of δ-aminolevulinic acid, one of the intermediate compounds in the biosynthetic pathway.
Plants that are fed by ALA accumulate high and toxic levels of protochlorophyllide, as do mutants with a disrupted regulatory system. Arabidopsis FLU mutant with damaged regulation can survive only either in a continuous darkness or under continuous light, when the plant is capable to convert all produced protochlorophyllide into chlorophyll and do not overaccumulate it despite of the lack of regulation. In barley Tigrina mutant light kills the majority of the leaf tissue that has developed in the darkness, but part of the leaf that originated during the day survives; as a result, the leaves are covered by white stripes of necrotic regions, the number of the white stripes is close to the age of the leaf in days. Green regions survive the subsequent nights because the synthesis of chlorophyll in the mature leaf tissue is reduced anyway. In spite of numerous past attempts to find the mutant that overacumulates protochlorophyllide under usual conditions, only one such gene is known. Flu is a nuclear-encoded, chloroplast-located protein that appears containing only protein-protein interaction sites.
It is not known which other proteins interact through this linker. The regulatory protein is a transmembrane protein, located in the thylakoid membrane, it was discovered that Tigrina mutants in barley, known a long time ago, are mutated in the same gene. It is not obvious. Flu is a single gene, not a member of the gene family. By the sequence similarity, a similar protein was found in Chlamydomonas algae, showing that this regulatory subsystem existed a long time before the angiosperms lost the independent conversion enzyme. In a different manner, the Chlamydomonas regulatory protein is more complex: It is larger, crosses the thylakoid membrane twice rather than once, contains more protein-protein interactions sites, undergoes alternative splicing, it appears that the regulatory system underwent simplification during evolution
The term broad-spectrum antibiotic can refer to an antibiotic that acts on the two major bacterial groups, gram-positive and gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial infection is suspected but the group of bacteria is unknown or when infection with multiple groups of bacteria is suspected; this is in contrast to a narrow-spectrum antibiotic, effective against only a specific group of bacteria. Although powerful, broad-spectrum antibiotics pose specific risks the disruption of native, normal bacteria and the development of antimicrobial resistance. An example of a used broad-spectrum antibiotic is ampicillin. Broad-spectrum antibiotics are properly used in the following situations: Empirically, when the causative organism is unknown, but delays in treatment would lead to worsening infection or spread of bacteria to other parts of the body; this occurs, for example, in meningitis, where the patient can become fatally ill within hours if broad-spectrum antibiotics are not initiated.
For drug-resistant bacteria that do not respond to narrow-spectrum antibiotics. In the case of superinfections, where there are multiple types of bacteria causing illness, thus warranting either a broad-spectrum antibiotic or combination antibiotic therapy. For prophylaxis in order to prevent bacterial infections occurring. For example, this can occur before surgery, to prevent infection during the operation, or for patients with immunosuppression who are at high-risk for dangerous bacterial infections. Antibiotics are grouped by their ability to act on different bacterial groups. Although bacteria are biologically classified using taxonomy, disease-causing bacteria have been classified by their microscopic appearance and chemical function; the morphology of the organism may be classified as cocci, bacilli, spiral-shaped or pleomorphic. Additional classification occurs through the organism's ability to take up the Gram stain and counter-stain. Further classification includes their requirement for oxygen, patterns of hemolysis, or other chemical properties.
The most encountered groupings of bacteria include gram-positive cocci, gram-negative bacilli, atypical bacteria, anaerobic bacteria. Antibiotics are grouped by their ability to act on different bacterial groups. For example, 1st-generation cephalosporins are effective against gram-positive bacteria, while 4th-generation cephalosporins are effective against gram-negative bacteria. Empiric antibiotic therapy refers to the use of antibiotics to treat a suspected bacterial infection despite lack of a specific bacterial diagnosis. Definitive diagnosis of the species of bacteria occurs through culture of blood, sputum, or urine, can be delayed by 24 to 72 hours. Antibiotics are given after the culture specimen has been taken from the patient in order to preserve the bacteria in the specimen and ensure accurate diagnosis. Alternatively, some species may be identified through a stool test. Clinicians use a step-wise approach to determining appropriate empiric therapy. First, the potential diagnoses are established and any predisposing risk factors are determined.
The most bacterial species for this type of infection are identified. Lastly, an antibiotic or group of antibiotics are chosen that are reliably effective against the potential species of bacteria. Clinicians aim to choose empiric antibiotic combinations that cover all appropriate bacteria but minimize coverage of inappropriate bacteria, as to reduce the incidence of antimicrobial resistance. Narrow-spectrum antibiotics have been shown to be just as effective as broad-spectrum alternatives for children with acute bacterial upper respiratory tract infections, have a lower risk of side effects in children. A community-wide antibiogram that lists the susceptibility of community-acquired and hospital-acquired bacteria is helpful in guiding empiric therapy. Many professional organizations publish guidelines for empiric antibiotic therapy, as do hospitals, with their choices tailored for their specific resistance patterns. Many of these guidelines offer guidance on antibiotic dose and duration of therapy.
Once a specific species has been identified and its susceptibilities determined, antibiotics can be "narrowed" to a medication which targets a more specific range of bacteria. If no specific species are identified, patients may continue on the empiric regimen. There are an estimated 10-100 trillion multiple organisms; as a side-effect of therapy, antibiotics can change the body's normal microbial content by attacking indiscriminately both the pathological and occurring, beneficial or harmless bacteria found in the intestines and bladder. The destruction of the body's normal bacterial flora is thought to disrupt immunity and lead to a relative overgrowth in some bacteria or fungi. An overgrowth of drug-resistant microorganisms can lead to a secondary infection such as Clostridium difficile or candidiasis; this side-effect is more with the use of broad-spe