Hemoglobin
Hemoglobin or haemoglobin, abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates as well as the tissues of some invertebrates. Haemoglobin in the blood carries oxygen from the gills to the rest of the body. There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism. A healthy individual has 12 to 16 grams of haemoglobin in every 100 ml of blood. In mammals, the protein makes up about 96% of the red blood cells' dry content, around 35% of the total content. Haemoglobin has an oxygen-binding capacity of 1.34 mL O2 per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood. The mammalian hemoglobin molecule can bind up to four oxygen molecules. Hemoglobin is involved in the transport of other gases: It carries some of the body's respiratory carbon dioxide as carbaminohemoglobin, in which CO2 is bound to the heme protein.
The molecule carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, releasing it at the same time as oxygen. Haemoglobin is found outside red blood cells and their progenitor lines. Other cells that contain haemoglobin include the A9 dopaminergic neurons in the substantia nigra, alveolar cells, retinal pigment epithelium, mesangial cells in the kidney, endometrial cells, cervical cells and vaginal epithelial cells. In these tissues, haemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism. Haemoglobin and haemoglobin-like molecules are found in many invertebrates and plants. In these organisms, haemoglobins may carry oxygen, or they may act to transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant of the molecule, called leghaemoglobin, is used to scavenge oxygen away from anaerobic systems, such as the nitrogen-fixing nodules of leguminous plants, before the oxygen can poison the system.
In 1825 J. F. Engelhard discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron he calculated the molecular mass of hemoglobin to n × 16000, the first determination of a protein's molecular mass; this "hasty conclusion" drew a lot of ridicule at the time from scientists who could not believe that any molecule could be that big. Gilbert Smithson Adair confirmed Engelhard's results in 1925 by measuring the osmotic pressure of hemoglobin solutions; the oxygen-carrying property of hemoglobin was discovered by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation was described a few years by Felix Hoppe-Seyler. In 1959, Max Perutz determined the molecular structure of hemoglobin by X-ray crystallography.
This work resulted in his sharing with John Kendrew the 1962 Nobel Prize in Chemistry for their studies of the structures of globular proteins. The role of hemoglobin in the blood was elucidated by French physiologist Claude Bernard; the name hemoglobin is derived from the words heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces; the most common type of hemoglobin in mammals contains four such subunits. Hemoglobin consists of protein subunits, these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides; the amino acid sequence of any polypeptide created by a cell is in turn determined by the stretches of DNA called genes. In all proteins, it is the amino acid sequence that determines the protein's chemical properties and function. There is more than one hemoglobin gene: in humans, hemoglobin A is coded for by the genes, HBA1, HBA2, HBB.
The amino acid sequences of the globin proteins in hemoglobins differ between species. These differences grow with evolutionary distance between species. For example, the most common hemoglobin sequences in humans and chimpanzees are nearly identical, differing by only one amino acid in both the alpha and the beta globin protein chains; these differences grow larger between less related species. Within a species, different variants of hemoglobin always exist, although one sequence is a "most common" one in each species. Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Many of these mutant forms of hemoglobin cause no disease; some of these mutant forms of hemoglobin, cause a group of hereditary diseases termed the hemoglobinopathies. The best known hemoglobinopathy is sickle-cell disease, the first human disease whose mechanism was understood at the molecular level. A separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation.
All these diseases produce anemia. Variations in hemoglobin amino acid sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to
Tetrameric protein
A tetrameric protein is a protein with a quaternary structure of four subunits. Homotetramers have four identical subunits, heterotetramers are complexes of different subunits. A tetramer can be assembled as dimer of dimers with two homodimer subunits, or two heterodimer subunits; the interactions between subunits forming a tetramer is determined by non covalent interaction. Hydrophobic effects, hydrogen bonds and electrostatic interactions are the primary sources for this binding process between subunits. For homotetrameric proteins such as Sorbitol dehydrogenase, the structure is believed to have evolved going from a monomeric to a dimeric and a tetrameric structure in evolution; the binding process in SDH and many other tetrameric enzymes can be described by the gain in free energy which can be determined from the rate of association and dissociation. The following image shows the assembly of the four subunits in SDH. Hydrogen bonding networks between subunits has been shown to be important for the stability of the tetrameric quaternary protein structure.
For example, a study of SDH which used diverse methods such as protein sequence alignments, structural comparisons, energy calculations, gel filtration experiments and enzyme kinetics experiments, could reveal an important hydrogen bonding network which stabilizes the tetrameric quaternary structure in mammalian SDH. In immunology, MHC tetramers can be used in tetramer assays, to quantify numbers of antigen-specific T cells. MHC tetramers are based on recombinant class I molecules that, through the action of bacterial BirA, have been biotinylated; these molecules are folded with the peptide of interest and β2M and tetramerized by a fluorescently labeled streptavidin. This tetramer reagent will label T cells that express T cell receptors that are specific for a given peptide-MHC complex. For example, a Kb/FAPGNYPAL tetramer will bind to Sendai virus specific cytotoxic T cell in a C57BL/6 mouse. Antigen specific responses can be measured as CD8+, tetramer+ T cells as a fraction of all CD8+ lymphocytes.
The reason for using a tetramer, as opposed to a single labeled MHC class I molecule is that the tetrahedral tetramers can bind to three TCRs at once, allowing specific binding in spite of the low affinity of the typical class I-peptide-TCR interaction. MHC class II tetramers can be made although these are more difficult to work with practically. T-cell Group - Cardiff University
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid. The active site of most carbonic anhydrases contains a zinc ion, they are therefore classified as metalloenzymes. The enzyme helps transport carbon dioxide. Carbonic anhydrase helps regulate fluid balance. Depending on its location, the role of the enzyme changes slightly. For example, carbonic anhydrase produces acid in the stomach lining. In the kidney, the control of bicarbonate ions influences the water content of the cell; the control of bicarbonate ions influences the water content in the eyes, if the enzyme does not work properly, a buildup of fluid can lead to glaucoma. The reaction catalyzed by carbonic anhydrase is: HCO3- + H+ ↽ − ⇀ CO2 + H2OCarbonic acid has a pKa of around 6.36, so at pH 7 a small percentage of the bicarbonate is protonated. Carbonic anhydrase is one of the fastest enzymes, its rate is limited by the diffusion rate of its substrates.
Typical catalytic rates of the different forms of this enzyme ranging between 104 and 106 reactions per second. The uncatalyzed reverse reaction is slow; this is why a carbonated drink does not degas when opening the container. An anhydrase is defined as an enzyme that catalyzes the removal of a water molecule from a compound, so it is this "reverse" reaction that gives carbonic anhydrase its name, because it removes a water molecule from carbonic acid. In the lungs carbonic anhydrase converts bicarbonate to carbon dioxide, suited for exhalation. A zinc prosthetic group in the enzyme is coordinated in three positions by histidine side-chains; the fourth coordination position is occupied by water. A fourth histidine is close to the water ligand, facilitating formation of Zn-OH center, which binds CO2 to give a zinc bicarbonate; the construct is an example of general acid – general base catalysis. The active site features a pocket suited for carbon dioxide, bringing it close to the hydroxide group.
Carbonic anhydrase was found in the red blood cells of cows. At least five distinct CA families are recognized: α, β, γ, δ and ζ; these families have no significant amino acid sequence similarity and in most cases are thought to be an example of convergent evolution. The α-CAs are found in humans. Vertebrates and some bacteria have this family of CAs; the CA enzymes found in mammals are divided into four broad subgroups, which, in turn consist of several isoforms: the cytosolic CAs mitochondrial CAs secreted CAs membrane-associated CAs There are three additional "acatalytic" CA isoforms whose functions remain unclear. Most prokaryotic and plant chloroplast CAs belong to the beta family. Two signature patterns for this family have been identified: C--D-S-R--x- --A--x--x--x-G-H-x-C-G The gamma class of CAs come from methanogens, methane-producing bacteria that grow in hot springs; the delta class of CAs has been described in diatoms. The distinction of this class of CA has come into question, however.
The zeta class of CAs occurs in bacteria in a few chemolithotrophs and marine cyanobacteria that contain cso-carboxysomes. Recent 3-dimensional analyses suggest that ζ-CA bears some structural resemblance to β-CA near the metal ion site. Thus, the two forms may be distantly related though the underlying amino acid sequence has since diverged considerably; the eta family of CAs was found in organisms of the genus Plasmodium. These are a group of enzymes thought to belong to the alpha family of CAs, however it has been demonstrated that η-CAs have unique features, such as their metal ion coordination pattern. Several forms of carbonic anhydrase occur in nature. In the best-studied α-carbonic anhydrase form present in animals, the zinc ion is coordinated by the imidazole rings of 3 histidine residues, His94, His96, His119; the primary function of the enzyme in animals is to interconvert carbon dioxide and bicarbonate to maintain acid-base balance in blood and other tissues, to help transport carbon dioxide out of tissues.
There are at least 14 different isoforms in mammals. Plants contain a different form called β-carbonic anhydrase, from an evolutionary standpoint, is a distinct enzyme, but participates in the same reaction and uses a zinc ion in its active site. In plants, carbonic anhydrase helps raise the concentration of CO2 within the chloroplast in order to increase the carboxylation rate of the enzyme RuBisCO; this is the reaction that integrates CO2 into organic carbon sugars during photosynthesis, can use only the CO2 form of carbon, not carbonic acid or bicarbonate. Marine diatoms have been found to express a new form of ζ carbonic anhydrase. T. weissflogii, a species of phytoplankton common to many marine ecosystems, was found to contain carbonic anhydrase with a cadmium ion in place of zinc. It had been believed that cadmium was a toxic metal with no biological function whatsoever. However, this species of phytoplankton appears to have adapted to the low levels of zinc in the ocean by using cadmium when there is not e
Humpback whale
The humpback whale is a species of baleen whale. One of the larger rorqual species, adults range in length from 12–16 m and weigh around 25–30 metric tons; the humpback has a distinctive body shape, with a knobbly head. It is known for breaching and other distinctive surface behaviors, making it popular with whale watchers. Males produce a complex song lasting 10 to 20 minutes, its purpose is not clear. Found in oceans and seas around the world, humpback whales migrate up to 25,000 km each year, they feed in polar waters, migrate to tropical or subtropical waters to breed and give birth and living off their fat reserves. Their diet consists of krill and small fish. Humpbacks have a diverse repertoire of feeding methods, including the bubble net technique. Like other large whales, the humpback was a target for the whaling industry. Once hunted to the brink of extinction, its population fell by an estimated 90% before a 1966 moratorium. While stocks have recovered to some 80,000 animals worldwide, entanglement in fishing gear, collisions with ships and noise pollution continue to impact on the species.
Humpback whales are rorquals, members of the Balaenopteridae family that includes the blue, Bryde's, sei and minke whales. The rorquals are believed to have diverged from the other families of the suborder Mysticeti as long ago as the middle Miocene era. However, it is not known. Though related to the giant whales of the genus Balaenoptera, the humpback is the sole member of its genus. Recent DNA sequencing has indicated the humpback is more related to certain rorquals the fin whale and the gray, than it is to others such as the minke; the humpback was first identified as baleine de la Nouvelle Angleterre by Mathurin Jacques Brisson in his Regnum Animale of 1756. In 1781, Georg Heinrich Borowski described the species, converting Brisson's name to its Latin equivalent, Balaena novaeangliae. In 1804, Lacépède shifted the humpback from the family Balaenidae. In 1846, John Edward Gray created the genus Megaptera, classifying the humpback as Megaptera longipinna, but in 1932, Remington Kellogg reverted the species names to use Borowski's novaeangliae.
The common name is derived from the curving of their backs. The generic name Megaptera from the Greek mega-/μεγα- "giant" and ptera/πτερα "wing", refers to their large front flippers; the specific name means "New Englander" and was given by Brisson due to regular sightings of humpbacks off the coast of New England. Genetic research in mid-2014 by the British Antarctic Survey confirmed that the separate populations in the North Atlantic, North Pacific and Southern Oceans are more distinct than thought; some biologists believe that these should be regarded as separate subspecies and that they are evolving independently. Humpbacks can be identified by their stocky body, obvious hump, black dorsal coloring and elongated pectoral fins; the head and lower jaw are covered with knobs called tubercles, which are hair follicles and are characteristic of the species. The fluked tail, which rises above the surface when diving, has wavy trailing edges. Humpbacks have 270 to 400 darkly colored baleen plates on each side of their mouths.
The plates measure from 18 in in the front to about 3 ft in the back, behind the hinge. Ventral grooves run from the lower jaw to the umbilicus, about halfway along the underside of the body; these grooves are less numerous than in other rorquals, but are wide. The female has a hemispherical lobe about 15 cm in diameter in her genital region; this visually distinguishes females. The male's penis remains hidden in the genital slit. Grown males average 13–14 m. Females are larger at 15–16 m; the largest humpback on record, according to whaling records, was a female killed in the Caribbean. The largest measured by the scientists of the Discovery Committee were a female 14.9 m and a male 14.75 m, although this was out of a sample size of only 63 whales. Body mass is in the range of 25–30 metric tons, with large specimens weighing over 40 metric tons. Newborn calves are the length of their mother's head. At birth, calves measure 6 m at 2 short tons, they nurse for about six months mix nursing and independent feeding for six months more.
Humpback milk is 50 % pink in color. Females reach sexual maturity at age five. Males reach sexual maturity around seven years of age; the long black and white tail fin can be up to a third of body length. Several hypotheses attempt to explain the humpback's pectoral fins, which are proportionally the longest fins of any cetacean; the higher maneuverability afforded by long fins and the usefulness of the increased surface area for temperature control when migrating between warm and cold climates supported this adaptation. The varying patterns on the tail flukes distinguish individual animals. A study using data from 1973 to 1998 on whales in the North Atlantic gave researchers detailed information on gestation times, growth rates and calving periods, as well as allowing
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in all mammals. It is distantly related to hemoglobin, the iron- and oxygen-binding protein in blood in the red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury, it is an abnormal finding, can be diagnostically relevant when found in blood. Myoglobin is the primary oxygen-carrying pigment of muscle tissues. High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with high abundance of myoglobin. Myoglobin is found in Type I muscle, Type II A and Type II B, but most texts consider myoglobin not to be found in smooth muscle. Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography; this achievement was reported in 1958 by associates. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.
Despite being one of the most studied proteins in biology, its physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin can be viable and fertile but show many cellular and physiological adaptations to overcome the loss. Through observing these changes in myoglobin-deplete mice, it is hypothesised that myoglobin function relates to increased oxygen transport to muscle, oxygen storage and as a scavenger of reactive oxygen species. In humans myoglobin is encoded by the MB gene. Myoglobin can take the forms oxymyoglobin and metmyoglobin, analogously to hemoglobin taking the forms oxyhemoglobin, carboxyhemoglobin, methemoglobin. Like hemoglobin, myoglobin is a cytoplasmic protein, it harbors only one heme group. Although its heme group is identical to those in Hb, Mb has a higher affinity for oxygen than does hemoglobin; this difference is related to its different role: whereas hemoglobin transports oxygen, myoglobin's function is to store oxygen. Myoglobin contains hemes, pigments responsible for the colour of red meat.
The colour that meat takes is determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous oxidation state bound to an oxygen molecule. Meat cooked well done is brown because the iron atom is now in the ferric oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide. Grilled meats can take on a pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide. Raw meat packed in a carbon monoxide atmosphere shows this same pink "smoke ring" due to the same principles. Notably, the surface of this raw meat displays the pink color, associated in consumers' minds with fresh meat; this artificially induced pink color can persist up to one year. Hormel and Cargill are both reported to use this meat-packing process, meat treated this way has been in the consumer market since 2003. Myoglobin is released from damaged muscle tissue, which has high concentrations of myoglobin.
The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute kidney injury. It is not the myoglobin itself, toxic but the ferrihemate portion, dissociated from myoglobin in acidic environments. Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction and thus CK-MB, cardiac Troponin, ECG, clinical signs should be taken into account to make the diagnosis. Myoglobin belongs to the globin superfamily of proteins, as with other globins, consists of eight alpha helices connected by loops. Myoglobin contains 154 amino acids. Myoglobin contains a porphyrin ring with an iron at its center. A proximal histidine group is attached directly to iron, a distal histidine group hovers near the opposite face; the distal imidazole is not bonded to the iron but is available to interact with the substrate O2. This interaction encourages the binding of O2, but not carbon monoxide, which still binds about 240× more than O2.
The binding of O2 causes substantial structural change at the Fe center, which shrinks in radius and moves into the center of N4 pocket. O2-binding induces "spin-pairing": the five-coordinate ferrous deoxy form is high spin and the six coordinate oxy form is low spin and diamagnetic. Many models of myoglobin have been synthesized as part of a broad interest in transition metal dioxygen complexes. A well known example is the picket fence porphyrin, which consists of a ferrous complex of a sterically bulky derivative of tetraphenylporphyrin. In the presence of an imidazole ligand, this ferrous complex reversibly binds O2; the O2 substrate adopts a bent geometry. A key property of this model is the slow formation of the μ-oxo dimer, an inactive diferric state. In nature, such deactivation pathways are suppressed by protein matrix that prevents close approach of the Fe-porphyrin assemblies. Cytoglobin Hemoglobin Hemoprotein Neuroglobin Phytoglobin Myoglobinuria - The presence of myoglobin in the urine Ischemia-reperfusion injury of the appendicular musculoskeletal system Online Mendelian Inheritance in Man 160000 human genetics The Myoglobin Protein Protein Database featured mole
Elephant
Elephants are large mammals of the family Elephantidae in the order Proboscidea. Three species are recognised: the African bush elephant, the African forest elephant, the Asian elephant. Elephants are scattered throughout sub-Saharan Africa, South Asia, Southeast Asia. Elephantidae is the only surviving family of the order Proboscidea. All elephants have several distinctive features, the most notable of, a long trunk, used for many purposes breathing, lifting water, grasping objects, their incisors grow into tusks, which can serve as weapons and as tools for moving objects and digging. Elephants' large ear flaps help to control their body temperature, their pillar-like legs can carry their great weight. African elephants have larger ears and concave backs while Asian elephants have smaller ears and convex or level backs. Elephants are herbivorous and can be found in different habitats including savannahs, forests and marshes, they prefer to stay near water. They are considered to be a keystone species due to their impact on their environments.
Other animals tend to keep their distance from elephants while predators, such as lions, tigers and any wild dogs target only young elephants. Elephants have a fission -- fusion society. Females tend to live in family groups, which can consist of one female with her calves or several related females with offspring; the groups are led by an individual known as the matriarch the oldest cow. Males leave their family groups when they may live alone or with other males. Adult bulls interact with family groups when looking for a mate and enter a state of increased testosterone and aggression known as musth, which helps them gain dominance and reproductive success. Calves are the centre of attention in their family groups and rely on their mothers for as long as three years. Elephants can live up to 70 years in the wild, they communicate by touch, sight and sound. Elephant intelligence has been compared with that of cetaceans, they appear to show empathy for dying or dead individuals of their kind. African elephants are listed as vulnerable by the International Union for Conservation of Nature while the Asian elephant is classed as endangered.
One of the biggest threats to elephant populations is the ivory trade, as the animals are poached for their ivory tusks. Other threats to wild elephants include habitat destruction and conflicts with local people. Elephants are used as working animals in Asia. In the past, they were used in war. Elephants are recognisable and have been featured in art, religion and popular culture; the word "elephant" is based on the Latin elephas, the Latinised form of the Greek ἐλέφας from a non-Indo-European language Phoenician. It is attested in Mycenaean Greek as e-re-pa in Linear B syllabic script; as in Mycenaean Greek, Homer used the Greek word to mean ivory, but after the time of Herodotus, it referred to the animal. The word "elephant" was borrowed from Old French oliphant. Loxodonta, the generic name for the African elephants, is Greek for "oblique-sided tooth". Elephants belong to the family Elephantidae, the sole remaining family within the order Proboscidea which belongs to the superorder Afrotheria.
Their closest extant relatives are the sirenians and the hyraxes, with which they share the clade Paenungulata within the superorder Afrotheria. Elephants and sirenians are further grouped in the clade Tethytheria. Three species of elephants are recognised. African elephants have larger ears, a concave back, more wrinkled skin, a sloping abdomen, two finger-like extensions at the tip of the trunk. Asian elephants have smaller ears, a convex or level back, smoother skin, a horizontal abdomen that sags in the middle and one extension at the tip of the trunk; the looped ridges on the molars are narrower in the Asian elephant while those of the African are more diamond-shaped. The Asian elephant has dorsal bumps on its head and some patches of depigmentation on its skin. Swedish zoologist Carl Linnaeus first described the genus Elephas and an elephant from Sri Lanka under the binomial Elephas maximus in 1758. In 1798, Georges Cuvier classified the Indian elephant under the binomial Elephas indicus.
Dutch zoologist Coenraad Jacob Temminck described the Sumatran elephant in 1847 under the binomial Elephas sumatranus. English zoologist Frederick Nutter Chasen classified all three as subspecies of the Asian elephant in 1940. Asian elephants vary geographically in their amount of depigmentation; the Sri Lankan elephant inhabits Sri Lanka, the Indian elephant is native to mainland Asia, the Sumatran elephant is found in Sumatra. O
