Enzymes are macromolecular biological catalysts. Enzymes accelerate chemical reactions; the molecules upon which enzymes may act are called substrates and the enzyme converts the substrates into different molecules known as products. All metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps; the study of enzymes is called enzymology and a new field of pseudoenzyme analysis has grown up, recognising that during evolution, some enzymes have lost the ability to carry out biological catalysis, reflected in their amino acid sequences and unusual'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins; the latter are called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction rate 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 otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. 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, activators are molecules that increase activity. Many therapeutic drugs and poisons are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal temperature and pH, many enzymes are denatured when exposed to excessive heat, losing their structure and catalytic properties; some enzymes are used commercially, in the synthesis of antibiotics. Some household products use enzymes to speed up chemical reactions: enzymes in biological washing powders break down protein, starch or fat stains on clothes, enzymes in meat tenderizer break down proteins into smaller molecules, making the meat easier to chew.
By the late 17th and early 18th centuries, the digestion of meat by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified. French chemist Anselme Payen was the first to discover an enzyme, diastase, in 1833. A few decades when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that this fermentation was caused by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms, 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, which comes from Greek ἔνζυμον, "leavened" or "in yeast", to describe this process. The word enzyme was used to refer to nonliving substances such as pepsin, 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 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 Buchner's example, enzymes are named according to the reaction they carry out: the suffix -ase is combined with the name of the substrate or to the type of reaction; the biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others argued that proteins were carriers for the true enzymes and that proteins per se were incapable of catalysis. In 1926, James B. Sumner crystallized it; the conclusion that pure proteins can be enzymes was definitively demonstrated by John Howard Northrop and Wendell Meredith Stanley, who worked on the digestive enzymes pepsin and chymotrypsin.
These three scientists were awarded the 1946 Nobel Prize in Chemistry. The discovery that enzymes could be crystallized allowed their structures to be solved by x-ray crystallography; this was first done for lysozyme, an enzyme found in tears and egg whites that digests the coating of some bacteria. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail. An enzyme's name is derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase. Examples are alcohol dehydrogenase and DNA polymerase. Different enzymes that catalyze the same chemical reaction are called isozymes; the International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers. The first number broadly classifies the enzyme based on its mechanism; the top-level classification is: EC 1, Oxidoreductases: catalyze oxidation/reducti
In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA; the RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait; these genes make up different DNA sequences called genotypes. Genotypes along with developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions; some genetic traits are visible, such as eye color or number of limbs, some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life. Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population; these alleles encode different versions of a protein, which cause different phenotypical traits.
Usage of the term "having a gene" refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection / survival of the fittest and genetic drift of the alleles; the concept of a gene continues to be refined. For example, regulatory regions of a gene can be far removed from its coding regions, coding regions can be split into several exons; some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or by regulation of gene expression; the term gene was introduced by Danish botanist, plant physiologist and geneticist Wilhelm Johannsen in 1909. It is inspired by the ancient Greek: γόνος, that means offspring and procreation; the existence of discrete inheritable units was first suggested by Gregor Mendel. From 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring.
He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics; this description prefigured Wilhelm Johannsen's distinction between phenotype. Mendel was the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilisation process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles. Mendel's work went unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries, Carl Correns, Erich von Tschermak, who reached similar conclusions in their own research.
In 1889, Hugo de Vries published his book Intracellular Pangenesis, in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes", after Darwin's 1868 pangenesis theory. Sixteen years in 1905, Wilhelm Johannsen introduced the term'gene' and William Bateson that of'genetics' while Eduard Strasburger, amongst others, still used the term'pangene' for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s; the structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.
In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination and arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 showed that individual genes have a simple linear structure and are to be equivalent to a linear section of DNA. Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, transcribed from DNA; this dogma has since been shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics. In 1972, Walter Fiers and his team were the first to determine the sequence of a gene: that of Bacteriophage MS2 coat protein; the subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool.
An automated version of the Sanger method was used in early phases of the
Glycosyltransferases are enzymes that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar to a nucleophilic glycosyl acceptor molecule, the nucleophile of which can be oxygen- carbon-, nitrogen-, or sulfur-based; the result of glycosyl transfer can be a carbohydrate, oligosaccharide, or a polysaccharide. Some glycosyltransferases catalyse transfer to inorganic water. Glycosyl transfer can occur to protein residues to tyrosine, serine, or threonine to give O-linked glycoproteins, or to asparagine to give N-linked glycoproteins. Mannosyl groups may be transferred to tryptophan to generate C-mannosyl tryptophan, abundant in eukaryotes. Transferases may use lipids as an acceptor, forming glycolipids, use lipid-linked sugar phosphate donors, such as dolichol phosphates. Glycosyltransferases that use sugar nucleotide donors are Leloir enzymes, after Luis F. Leloir, the scientist who discovered the first sugar nucleotide and who received the 1970 Nobel Prize in Chemistry for his work on carbohydrate metabolism.
Glycosyltransferases that use non-nucleotide donors such as dolichol or polyprenol pyrophosphate are non-Leloir glycosyltransferases. Mammals use only 9 sugar nucleotide donors for glycosyltransferases: UDP-glucose, UDP-galactose, UDP-GlcNAc, UDP-GalNAc, UDP-xylose, UDP-glucuronic acid, GDP-mannose, GDP-fucose, CMP-sialic acid; the phosphate of these donor molecules are coordinated by divalent cations such as manganese, however metal independent enzymes exist. Many glycosyltransferases are single-pass transmembrane proteins, they are anchored to membranes of Golgi apparatus Glycosyltransferases can be segregated into "retaining" or "inverting" enzymes according to whether the stereochemistry of the donor's anomeric bond is retained or inverted during the transfer; the inverting mechanism is straightforward, requiring a single nucleophilic attack from the accepting atom to invert stereochemistry. The retaining mechanism has been a matter of debate, but there exists strong evidence against a double displacement mechanism or a dissociative mechanism.
An "orthogonal associative" mechanism has been proposed which, akin to the inverting enzymes, requires only a single nucleophilic attack from an acceptor from a non-linear angle to achieve anomer retention. The recent discovery of the reversibility of many reactions catalyzed by inverting glycosyltransferases served as a paradigm shift in the field and raises questions regarding the designation of sugar nucleotides as'activated' donors. Sequence-based classification methods have proven to be a powerful way of generating hypotheses for protein function based on sequence alignment to related proteins; the carbohydrate-active enzyme database presents a sequence-based classification of glycosyltransferases into over 90 families. The same three-dimensional fold is expected to occur within each of the families. In contrast to the diversity of 3D structures observed for glycoside hydrolases, glycosyltransferase have a much smaller range of structures. In fact, according to the Structural Classification of Proteins database, only three different folds have been observed for glycosyltransferases Very a new glycosyltransferase fold was identified for the glycosyltransferases involved in the biosynthesis of the NAG-NAM polymer backbone of peptidoglycan.
Many inhibitors of glycosyltransferases are known. Some of these are natural products, such as moenomycin, an inhibitor of peptidoglycan glycosyltransferases, the nikkomycins, inhibitors of chitin synthase, the echinocandins, inhibitors of fungal b-1,3-glucan synthases; some glycosyltransferase inhibitors are of use as antibiotics. Moenomycin is used in animal feed as a growth promoter. Caspofungin is in use as an antifungal agent. Ethambutol is an inhibitor of mycobacterial arabinotransferases and is used for the treatment of tuberculosis. Lufenuron is used to control fleas in animals; the ABO blood group system is determined by what type of glycosyltransferases are expressed in the body. The ABO gene locus expressing the glycosyltransferases has three main allelic forms: A, B, O; the A allele encodes 1-3-N-acetylgalactosaminyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, producing the A antigen. The B allele encodes 1-3-galactosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen.
In case of O allele the exon 6 contains a deletion. The O allele differs from the A allele by deletion of a single nucleotide - Guanine at position 261; the deletion causes a frameshift and results in translation of an entirely different protein that lacks enzymatic activity. This results in H antigen remaining unchanged in case of O groups; the combination of glycosyltransferases by both alleles present in each person determines whether there is an AB, A, B or O blood type. Glycosyltransferases have been used in the both targeted synthesis of specific glycoconjugates as well as the synthesis of differentially glycosylated libraries of drugs, biological probes or natural products in the context of drug discovery and drug development. Suitable enzymes can be produced recombinantly; as an alternative, whole cell-based systems using either endogenous glycosyl donors o
ABO blood group system
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. In human blood transfusions it is the most important of the 36 different blood type classification systems recognized. A rare mismatch in this, or any other serotype, can cause a serious fatal, adverse reaction after a transfusion, or a contra-indicated immune response to an organ transplant; the associated anti-A and anti-B antibodies are IgM antibodies, which are produced in the first years of life by sensitization to environmental substances, such as food and viruses. The ABO blood types were discovered by Karl Landsteiner in 1901, for which he received the Nobel Prize in Physiology or Medicine in 1930. ABO blood types are present in some other animals such as rodents and apes, including chimpanzees and gorillas; the ABO blood types were first discovered by an Austrian Physician Karl Landsteiner working at the Pathological-Anatomical Institute of the University of Vienna.
In 1900, he found that blood sera from different persons would clump together when mixed in test tubes, not only that some human blood agglutinated with animal blood. He wrote a two-sentence footnote: The serum of healthy human beings not only agglutinates animal red cells, but often those of human origin, from other individuals, it remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind. This was the first evidence that blood variation exists in humans – it was believed that all humans have similar blood; the next year, in 1901, he made a definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human bloods into three groups, namely group A, group B, group C, he defined that group, but never with its own type. Group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B.
This was the discovery of blood groups for which Landsteiner was awarded the Nobel Prize in Physiology or Medicine in 1930. In his paper, he called the specific blood group interactions as isoagglutination, introduced the concept of agglutinins, the actual basis of antigen-antibody reaction in ABO system, he asserted: may be said that there exist at least two different types of agglutinins, one in A, another one in B, both together in C. The red blood cells are inert to the agglutinins. Thus, he discovered two antibodies, his third group indicated absence of both A and B antigens, but contains anti-A and anti-B. The following year, his students Adriano Sturli and Alfred von Decastello discovered the fourth type. In 1910, Ludwik Hirszfeld and Emil Freiherr von Dungern introduced the term 0 for the group Landsteiner designated as C, AB for the type discovered by Sturli and von Decastello, they were the first to explain the genetic inheritance of the blood groups. Czech serologist Jan Janský independently introduced blood type classification in 1907 in a local journal.
He used the Roman numerical I, II, III, IV. Unbeknown to Janský, an American physician William L. Moss devised a different classification using the same numerical; these two systems created confusion and potential danger in medical practice. Moss's system was adopted in Britain, US, while Janský's was preferred in most European countries and some parts of US. To resolve the chaos, the American Association of Immunologists, the Society of American Bacteriologists, the Association of Pathologists and Bacteriologists made a joint recommendation in 1921 that the Jansky classification be adopted based on priority, but it was not followed where Moss's system had been used. In 1927, who had moved to the Rockefeller Institute for Medical Research in New York, as a member of a committee of the National Research Council concerned with blood grouping suggested to substitute Janský's and Moss's systems with the letters 0, A, B, AB; this classification was adopted by the National Research Council and became variously known as the National Research Council classification, the International classification, most popularly the "new" Landsteiner classification.
The new system was accepted and by the early 1950s, it was universally followed. The first practical use of blood typing in transfusion was by an American physician Reuben Ottenberg in 1907, and the large-scale application started during the First World War when citric acid was developed as blood clot prevention. Felix Bernstein demonstrated the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Finne et al. found that the human erythrocyte glycoproteins contain polylactosamine chains that contains ABH substances attached and represent the majority of the
In chemistry residue is whatever remains or acts as a contaminant after a given class of events. Residue may be the material remaining after a process of preparation, separation, or purification, such as distillation, evaporation, or filtration, it may denote the undesired by-products of a chemical reaction. Toxic chemical residues, wastes or contamination from other processes, are a concern in food safety. For example, the U. S. Food and Drug Administration and the Canadian Food Inspection Agency have guidelines for detecting chemical residues that are dangerous to consume. Residue may refer to an atom or a group of atoms that forms part of a molecule, such as a methyl group. In biochemistry and molecular biology, a residue refers to a specific monomer within the polymeric chain of a polysaccharide, protein or nucleic acid. One might say, "This protein consists of 118 amino acid residues" or "The histidine residue is considered to be basic because it contains an imidazole ring." Note that a residue is different from a moiety.
The concept that suggested this term is the nature of the condensation reaction by which such classes of monomeric building blocks, such as amino acids or monosaccharides, are strung together to form a polymeric chain, such as a polysaccharide or a peptide. A residue might be one amino acid in a polypeptide or one monosaccharide in a starch molecule
A base pair is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, Watson–Crick base pairs allow the DNA helix to maintain a regular helical structure, subtly dependent on its nucleotide sequence; the complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes. Intramolecular base pairs can occur within single-stranded nucleic acids.
This is important in RNA molecules, where Watson–Crick base pairs permit the formation of short double-stranded helices, a wide variety of non-Watson–Crick interactions allow RNAs to fold into a vast range of specific three-dimensional structures. In addition, base-pairing between transfer RNA and messenger RNA forms the basis for the molecular recognition events that result in the nucleotide sequence of mRNA becoming translated into the amino acid sequence of proteins via the genetic code; the size of an individual gene or an organism's entire genome is measured in base pairs because DNA is double-stranded. Hence, the number of total base pairs is equal to the number of nucleotides in one of the strands; the haploid human genome is estimated to be about 3.2 billion bases long and to contain 20,000–25,000 distinct protein-coding genes. A kilobase is a unit of measurement in molecular biology equal to 1000 base pairs of DNA or RNA; the total amount of related DNA base pairs on Earth is estimated at 5.0×1037 and weighs 50 billion tonnes.
In comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC. Hydrogen bonding is the chemical interaction. Appropriate geometrical correspondence of hydrogen bond donors and acceptors allows only the "right" pairs to form stably. DNA with high GC-content is more stable than DNA with low GC-content. But, contrary to popular belief, the hydrogen bonds do not stabilize the DNA significantly; the larger nucleobases and guanine, are members of a class of double-ringed chemical structures called purines. Purines are complementary only with pyrimidines: pyrimidine-pyrimidine pairings are energetically unfavorable because the molecules are too far apart for hydrogen bonding to be established. Purine-pyrimidine base-pairing of AT or GC or UA results in proper duplex structure; the only other purine-pyrimidine pairings would be AC and GT and UG. The GU pairing, with two hydrogen bonds, does occur often in RNA. Paired DNA and RNA molecules are comparatively stable at room temperature, but the two nucleotide strands will separate above a melting point, determined by the length of the molecules, the extent of mispairing, the GC content.
Higher GC content results in higher melting temperatures. On the converse, regions of a genome that need to separate — for example, the promoter regions for often-transcribed genes — are comparatively GC-poor. GC content and melting temperature must be taken into account when designing primers for PCR reactions; the following DNA sequences illustrate pair double-stranded patterns. By convention, the top strand is written from the 5' end to the 3' end. A base-paired DNA sequence: ATCGATTGAGCTCTAGCG TAGCTAACTCGAGATCGCThe corresponding RNA sequence, in which uracil is substituted for thymine in the RNA strand: AUCGAUUGAGCUCUAGCG UAGCUAACUCGAGAUCGC Chemical analogs of nucleotides can take the place of proper nucleotides and establish non-canonical base-pairing, leading to errors in DNA replication and DNA transcription; this is due to their isosteric chemistry. One common mutagenic base analog is 5-bromouracil, which resembles thymine but can base-pair to guanine in its enol form. Other chemicals, known as DNA intercalators, fit into the gap between adjacent bases on a single strand and induce frameshift mutations by "masquerading" as a base, causing the DNA replication machinery to skip or insert additional nucleotides at the intercalated site.
Most intercalators are known or suspected carcinogens. Examples include ethidium acridine. An unnatural base pair is a designed subunit of DNA, created in a laboratory and does not occur in nature. DNA sequences have been described which use newly created nucleobases to form a third base pair, in addition to the two ba
Chromosome 9 is one of the 23 pairs of chromosomes in humans. Humans have two copies of this chromosome, as they do with all chromosomes. Chromosome 9 spans about 138 million base pairs of nucleic acids and represents between 4 and 4.5 percent of the total DNA in cells. The following are some of the gene count estimates of human chromosome 9; because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies. Among various projects, the collaborative consensus coding sequence project takes an conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes; the following is a partial list of genes on human chromosome 9. For complete list, see the link in the infobox on the right; the following diseases are some of those related to genes on chromosome 9: National Institutes of Health. "Chromosome 9". Genetics Home Reference. Retrieved 2017-05-06. "Chromosome 9". Human Genome Project Information Archive 1990–2003.