1.
Hemagglutinin (influenza)
–
Influenza hemagglutinin or haemagglutinin is a glycoprotein found on the surface of influenza viruses. It is responsible for binding the virus to cells with sialic acid on the membranes and it is also responsible for the fusion of the viral envelope with the endosome membrane, after the pH has been reduced. The name hemagglutinin comes from the ability to cause red blood cells to clump together in vitro. HA has at least 18 different antigens and these subtypes are named H1 through H18. H16 was discovered in 2004 on influenza A viruses isolated from black-headed gulls from Sweden, h17 was discovered in 2012 in fruit bats. Most recently, H18 was discovered in a Peruvian bat in 2013, the first three hemagglutinins, H1, H2, and H3, are found in human influenza viruses. Viral neuraminidase is another protein found on the surface of influenza, influenza viruses are characterized by the type of HA and NA that they carry, hence H1N1, H5N2 etc. A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate and this finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, firstly, it allows the recognition of target vertebrate cells, accomplished through the binding to these cells sialic acid-containing receptors. Secondly, once bound it facilitates the entry of the genome into the target cells by causing the fusion of host endosomal membrane with the viral membrane. HA binds to the sialic acid which is present on the surface of its target cells. The cell then attempts to begin digesting the contents of the endosome by acidifying its interior, however, as soon as the pH within the endosome drops to about 6. This so-called fusion peptide acts like a grappling hook by inserting itself into the endosomal membrane. Once this has happened, the contents of the virus, including its RNA genome, are free to pour out into the cells cytoplasm, HA is a homotrimeric integral membrane glycoprotein. It is shaped like a cylinder, and is approximately 13.5 nanometres long, the three identical monomers that constitute HA are constructed into a central α helix coil, three spherical heads contain the sialic acid binding sites. HA monomers are synthesized as precursors that are glycosylated and cleaved into two smaller polypeptides, the HA1 and HA2 subunits. Each HA monomer consists of a long, helical chain anchored in the membrane by HA2, since hemagglutinin is the major surface protein of the influenza A virus and is essential to the entry process, it is the primary target of neutralizing antibodies. This is because these antibodies bind near the top of the hemagglutinin head, in contrast, some antibodies have been found to have no effect on attachment
2.
Influenza A virus subtype H5N1
–
Influenza A virus subtype H5N1, also known as A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species. It is enzootic in many populations, especially in Southeast Asia. One strain of HPAI A is spreading globally after first appearing in Asia and it is epizootic and panzootic, killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Many references to bird flu and H5N1 in the popular media refer to this strain, eleven outbreaks of H5N1 were reported worldwide in June 2008 in five countries compared to 65 outbreaks in June 2006 and 55 in June 2007. In July 2013 the WHO announced a total of 630 confirmed human cases which resulted in the deaths of 375 people since 2003. Several H5N1 vaccines have been developed and approved, and stockpiled by a number of countries, including the United States, Britain, France, Canada, HPAI A is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A risk factor for contracting the virus is handling of infected poultry and he called for adequate resources to fight what he sees as a major world threat to possibly billions of lives. Experts have identified key events marking the progression of a flu virus towards becoming pandemic. H5N1 may cause more than one influenza pandemic, as it is expected to continue mutating in birds regardless of whether humans develop herd immunity to a pandemic strain. Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1, the severity of the infection depends in large part on the state of the infected persons immune systems and whether they had been exposed to the strain before. No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu, the avian influenza hemagglutinin binds alpha 2-3 sialic acid receptors, while human influenza hemagglutinins bind alpha 2-6 sialic acid receptors. This means when the H5N1 strain infects humans, it will replicate in the respiratory tract. There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1. The reported mortality rate of highly pathogenic H5N1 avian influenza in a human is high, WHO data indicate 60% of cases classified as H5N1 resulted in death. However, there is evidence the actual mortality rate of avian flu could be much lower. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms, there have been studies of the levels of cytokines in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor-alpha, an associated with tissue destruction at sites of infection. Flu virus-induced increases in the level of cytokines is also associated with flu symptoms, including fever, chills, vomiting, tissue damage associated with pathogenic flu virus infection can ultimately result in death
3.
Amino acid
–
Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an acid are carbon, hydrogen, oxygen. About 500 amino acids are known and can be classified in many ways, in the form of proteins, amino acids comprise the second-largest component of human muscles, cells and other tissues. Outside proteins, amino acids perform critical roles in such as neurotransmitter transport. In biochemistry, amino acids having both the amine and the acid groups attached to the first carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids and they include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins. These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as standard amino acids. The other two are selenocysteine, and pyrrolysine, pyrrolysine and selenocysteine are encoded via variant codons, for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine is generally considered as a form of methionine rather than as a separate proteinogenic amino acid, codon–tRNA combinations not found in nature can also be used to expand the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids also play critical roles within the body. Nine proteinogenic amino acids are called essential for humans because they cannot be created from other compounds by the human body, others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species, because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production of drugs, biodegradable plastics, the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. Glycine and leucine were discovered in 1820, usage of the term amino acid in the English language is from 1898. Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis, in the structure shown at the top of the page, R represents a side chain specific to each amino acid. The carbon atom next to the group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as amino acids
4.
Sialic acid
–
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, Sialic acids are found widely distributed in animal tissues and to a lesser extent in other organisms, ranging from plants and fungi to yeasts and bacteria, mostly in glycoproteins and gangliosides. That is because it seems to have appeared late in evolution, however, it has been observed in Drosophila embryos and other insects and in the capsular polysaccharides of certain strains of bacteria. In humans the brain has the highest sialic acid concentration, where these acids play an important role in neural transmission, in general, the amino group bears either an acetyl or a glycolyl group, but other modifications have been described. The hydroxyl substituents may vary considerably, acetyl, lactyl, methyl, sulfate, the term sialic acid was first introduced by Swedish biochemist Gunnar Blix in 1952. The sialic acid family includes 43 derivatives of the nine-carbon sugar neuraminic acid, the numbering of the sialic acid structure begins at the carboxylate carbon and continues around the chain. The configuration that places the carboxylate in the position is the alpha-anomer. The alpha-anomer is the form that is found when sialic acid is bound to glycans, however, in solution, it is mainly in the beta-anomeric form. Sialic acid is synthesized by glucosamine 6 phosphate and acetyl CoA through a transferase and this becomes N-acetylmannosamine-6-P through epimerization, which reacts with phosphoenolpyruvate producing N-acetylneuraminic-9-P. This compound is synthesized in the nucleus of the animal cell, in bacterial systems, sialic acids are biosynthesized by an aldolase enzyme. The enzyme uses a derivative as a substrate, inserting three carbons from pyruvate into the resulting sialic acid structure. These enzymes can be used for synthesis of sialic acid derivatives. Sialic acid-rich glycoproteins bind selectin in humans and other organisms, metastatic cancer cells often express a high density of sialic acid-rich glycoproteins. This overexpression of sialic acid on surfaces creates a charge on cell membranes. This creates repulsion between cells and helps these late-stage cancer cells enter the blood stream, many bacteria also use sialic acid in their biology, although this is usually limited to bacteria that live in association with higher animals. Many of these incorporate sialic acid into cell surface features like their lipopolysaccharide and capsule, other bacteria simply use sialic acid as a good nutrient source, as it contains both carbon and nitrogen and can be converted to fructose-6-phosphate, which can then enter central metabolism. Sialic acid-rich oligosaccharides on the glycoconjugates found on surface membranes help keep water at the surface of cells, the sialic acid-rich regions contribute to creating a negative charge on the cells surfaces. Since water is a molecule with partial positive charges on both hydrogen atoms, it is attracted to cell surfaces and membranes
5.
Enzyme
–
Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
