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124-395: 5329 18793 ENSG00000011422 ENSMUSG00000046223 Q03405 P35456 NM_001005376 NM_001005377 NM_001301037 NM_002659 NM_011113 NP_001005376 NP_001005377 NP_001287966 NP_002650 NP_035243 The Urokinase receptor , also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 ( C luster of D ifferentiation 87 ),

248-520: A carboxyl group, and a variable side chain are bonded . Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids , have a great variety of chemical structures and properties; it is the combined effect of all of

372-470: A gene may be duplicated before it can mutate freely. However, this can also lead to complete loss of gene function and thus pseudo-genes . More commonly, single amino acid changes have limited consequences although some can change protein function substantially, especially in enzymes . For instance, many enzymes can change their substrate specificity by one or a few mutations. Changes in substrate specificity are facilitated by substrate promiscuity , i.e.

496-533: A peptide antagonist and with its native ligand, urokinase. All three three-finger domains are necessary for high affinity binding of the primary ligand, urokinase . In addition, uPAR also interacts with several other proteins, including vitronectin , the uPAR associated protein ( uPARAP ) and the integrin family of membrane proteins . It has been possible to express uPAR recombinantly in CHO-cells and S2 cells from Drosophila melanogaster . 4 out of 5 of

620-649: A German family. In the 20th century, smoking was common. There were social events like the smoke night which promoted the habit. The anti-tobacco movement in Nazi Germany did not reach across enemy lines during the Second World War, as anti-smoking groups quickly lost popular support. By the end of the Second World War, American cigarette manufacturers quickly reentered the German black market. Illegal smuggling of tobacco became prevalent, and leaders of

744-466: A biomarker of inflammation . Elevated suPAR is seen in chronic obstructive pulmonary disease , asthma , liver failure , heart failure , cardiovascular disease , and rheumatoid arthritis . Smokers have significantly higher suPAR compared to non-smokers. Urokinase receptors have been found to be highly expressed on senescent cells , leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice. The components of

868-552: A combination of sequence, structure and function, and they can be combined in many different ways. In an early study of 170,000 proteins, about two-thirds were assigned at least one domain, with larger proteins containing more domains (e.g. proteins larger than 600 amino acids having an average of more than 5 domains). Most proteins consist of linear polymers built from series of up to 20 different L -α- amino acids. All proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group,

992-403: A defined conformation . Proteins can interact with many types of molecules, including with other proteins , with lipids , with carbohydrates , and with DNA . It has been estimated that average-sized bacteria contain about 2 million proteins per cell (e.g. E. coli and Staphylococcus aureus ). Smaller bacteria, such as Mycoplasma or spirochetes contain fewer molecules, on

1116-529: A depressant effect, while higher doses have stimulant effect." A number of studies have established that cigarette sales and smoking follow distinct time-related patterns. For example, cigarette sales in the United States of America have been shown to follow a strongly seasonal pattern, with the high months being the months of summer, and the low months being the winter months. Similarly, smoking has been shown to follow distinct circadian patterns during

1240-851: A detailed review of the vegetable proteins at the Connecticut Agricultural Experiment Station . Then, working with Lafayette Mendel and applying Liebig's law of the minimum , which states that growth is limited by the scarcest resource, to the feeding of laboratory rats, the nutritionally essential amino acids were established. The work was continued and communicated by William Cumming Rose . The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, including those of blood, egg whites, and various toxins, as well as digestive and metabolic enzymes obtained from slaughterhouses. In

1364-498: A less significant part in adolescent smoking, with adolescents also reporting low levels of both normative and direct pressure to smoke cigarettes. Mere exposure to tobacco retailers may motivate smoking behaviour in adults. A similar study suggested that individuals may play a more active role in starting to smoke than has previously been thought and that social processes other than peer pressure also need to be taken into account. Another study's results indicated that peer pressure

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1488-432: A link between smoking and lung cancer in the late 1920s, leading to the first anti-smoking campaign in modern history, albeit one truncated by the collapse of Nazi Germany at the end of World War II . In 1950, British researchers demonstrated a clear relationship between smoking and cancer. Evidence continued to mount in the 1960s, which prompted political action against the practice. Rates of consumption since 1965 in

1612-478: A little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation , whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable 3D structure. But the boundary between the two is not well defined and usually lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of

1736-410: A particular cell or cell type is known as its proteome . The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by

1860-500: A protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments can provide information about the physiological role of a protein in the context of a cell or even a whole organism . In silico studies use computational methods to study proteins. Proteins may be purified from other cellular components using

1984-411: A protein is defined by the sequence of a gene, which is encoded in the genetic code . In general, the genetic code specifies 20 standard amino acids; but in certain organisms the genetic code can include selenocysteine and—in certain archaea — pyrrolysine . Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification , which alters

2108-542: A protein that fold into distinct structural units. Domains usually also have specific functions, such as enzymatic activities (e.g. kinase ) or they serve as binding modules (e.g. the SH3 domain binds to proline-rich sequences in other proteins). Short amino acid sequences within proteins often act as recognition sites for other proteins. For instance, SH3 domains typically bind to short PxxP motifs (i.e. 2 prolines [P], separated by two unspecified amino acids [x], although

2232-459: A readily accepted trade item and would often smoke it in ceremonial pipes , either in sacred ceremonies or to seal bargains. Adults as well as children enjoyed the practice. It was believed that tobacco was a gift from the Creator and that the exhaled tobacco smoke was capable of carrying one's thoughts and prayers to heaven. Apart from smoking, tobacco had uses as medicine. As a pain killer it

2356-486: A role in biological recognition phenomena involving cells and proteins. Receptors and hormones are highly specific binding proteins. Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse . Membrane proteins contain internal channels that allow such molecules to enter and exit

2480-406: A series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a " His-tag "),

2604-432: A solution known as a crude lysate . The resulting mixture can be purified using ultracentrifugation , which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles , and nucleic acids . Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate

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2728-451: A specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide . A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides . The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues in

2852-441: A variety of techniques such as ultracentrifugation , precipitation , electrophoresis , and chromatography ; the advent of genetic engineering has made possible a number of methods to facilitate purification. To perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis , in which a cell's membrane is disrupted and its internal contents released into

2976-432: A vast array of functions within organisms, including catalysing metabolic reactions , DNA replication , responding to stimuli , providing structure to cells and organisms , and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes , and which usually results in protein folding into

3100-536: Is a protein encoded in humans by the PLAUR gene . It is a multidomain glycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase (also known as uPA) on the cell surface. uPAR consists of three tandem LU domains , which are protein domains of the three-finger protein family. The structure of uPAR has been solved by X-ray crystallography in complex with

3224-523: Is a complex mixture of over 7,000 toxic chemicals , 98 of which are associated with an increased risk of cardiovascular disease and 69 of which are known to be carcinogenic . The most important chemicals causing cancer are those that produce DNA damage, since such damage appears to be the primary underlying cause of cancer. The most carcinogenic compounds in cigarette smoke are acrolein , formaldehyde , acrylonitrile , 1,3-butadiene , acetaldehyde , ethylene oxide , and isoprene . In addition to

3348-805: Is a greater cause of adolescent smoking. Psychologist Hans Eysenck (who later was questioned for nonplausible results and unsafe publications ) developed a personality profile for the typical smoker. Extraversion is the trait that is most associated with smoking, and smokers tend to be sociable, impulsive, risk taking, and excitement seeking individuals. The reasons given by some smokers for this activity have been categorized as addictive smoking , pleasure from smoking , tension reduction/relaxation , social smoking , stimulation , habit/automatism , and handling . There are gender differences in how much each of these reasons contribute, with females more likely than males to cite tension reduction/relaxation , stimulation and social smoking . Some smokers argue that

3472-431: Is a major risk factor for head and neck cancer . 72% of head and neck cancer cases are caused by using both alcohol and tobacco. This rises to 89% when looking specifically at laryngeal cancer . Cigarette smoking increases the risk of Crohn's disease as well as the severity of the course of the disease. It is also the number one cause of bladder cancer . Cigarette smoking has also been associated with sarcopenia ,

3596-421: Is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel , the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of different tags have been developed to help researchers purify specific proteins from complex mixtures. Tobacco smoking Tobacco smoking

3720-628: Is found in hard or filamentous structures such as hair , nails , feathers , hooves , and some animal shells . Some globular proteins can also play structural functions, for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that make up the cytoskeleton , which allows the cell to maintain its shape and size. Other proteins that serve structural functions are motor proteins such as myosin , kinesin , and dynein , which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and

3844-469: Is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second. The process of synthesizing a protein from an mRNA template is known as translation . The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges"

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3968-461: Is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure . Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction. Most proteins fold into unique 3D structures. The shape into which a protein naturally folds is known as its native conformation . Although many proteins can fold unassisted, simply through

4092-457: Is much less than that from cigarette smoke. Nicotine and cocaine activate similar patterns of neurons, which supports the existence of common substrates among these drugs. The absorbed nicotine mimics nicotinic acetylcholine which when bound to nicotinic acetylcholine receptors prevents the reuptake of acetylcholine thereby increasing that neurotransmitter in those areas of the body. These nicotinic acetylcholine receptors are located in

4216-404: Is often enormous—as much as 10 -fold increase in rate over the uncatalysed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme). The molecules bound and acted upon by enzymes are called substrates . Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with

4340-480: Is the proteolysis cascade initiated by the plasminogen activation system. uPAR binds urokinase and thus restricts plasminogen activation to the immediate vicinity of the cell membrane. When urokinase is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing a soluble form of the protein known as suPAR . Soluble urokinase plasminogen activator receptor (suPAR) has been found to be

4464-535: Is the code for methionine . Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon. Genes encoded in DNA are first transcribed into pre- messenger RNA (mRNA) by proteins such as RNA polymerase . Most organisms then process the pre-mRNA (also known as a primary transcript ) using various forms of post-transcriptional modification to form

4588-561: Is the practice of burning tobacco and ingesting the resulting smoke . The smoke may be inhaled, as is done with cigarettes , or simply released from the mouth, as is generally done with pipes and cigars . The practice is believed to have begun as early as 5000–3000 BC in Mesoamerica and South America . Tobacco was introduced to Eurasia in the late 17th century by European colonists , where it followed common trade routes. The practice encountered criticism from its first import into

4712-565: The British Doctors Study , a prospective study of some 40 thousand doctors for about 2.5 years, confirmed the suggestion, based on which the government issued advice that smoking and lung cancer rates were related. In January 1964, the United States Surgeon General 's Report on Smoking and Health likewise began suggesting the relationship between smoking and cancer. As scientific evidence mounted in

4836-489: The Patriarch of Moscow forbade the sale of tobacco, and sentenced men and women who flouted the ban to have their nostrils slit and their backs flayed. Pope Urban VIII likewise condemned smoking on holy places in a papal bull of 1624. Despite some concerted efforts, restrictions and bans were largely ignored. When James I of England , a staunch smoking opponent and the author of A Counterblaste to Tobacco , tried to curb

4960-483: The Western world onwards but embedded itself in certain strata of a number of societies before becoming widespread upon the introduction of automated cigarette-rolling apparatus. Smoking is the most common method of consuming tobacco, and tobacco is the most common substance smoked. The agricultural product is often mixed with additives and then combusted. The resulting smoke, which contains various active substances,

5084-492: The amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da . Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body, because it was generally believed that "flesh makes flesh." Around 1862, Karl Heinrich Ritthausen isolated the amino acid glutamic acid . Thomas Burr Osborne compiled

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5208-489: The depressant effect of smoking allows them to calm their nerves, often allowing for increased concentration. However, according to the Imperial College London , "Nicotine seems to provide both a stimulant and a depressant effect, and it is likely that the effect it has at any time is determined by the mood of the user, the environment and the circumstances of use. Studies have suggested that low doses have

5332-405: The developed world have either peaked or declined. However, they continue to climb in the developing world. As of 2008 to 2010, tobacco is used by about 49% of men and 11% of women aged 15 or older in fourteen low-income and middle-income countries (Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Russia, Thailand, Turkey, Ukraine, Uruguay and Vietnam), with about 80% of this usage in

5456-484: The developing world , however, tobacco consumption continued to rise at 3.4% in 2002. In Africa, smoking is in most areas considered to be modern, and many of the strong adverse opinions that prevail in the West receive much less attention. Today Russia leads as the top consumer of tobacco followed by Indonesia , Laos , Ukraine , Belarus , Greece, Jordan , and China. Tobacco is an agricultural product processed from

5580-1243: The developing world , however, tobacco consumption is rising by 3.4% per year as of 2002. The WHO in 2004 projected 58.8 million deaths to occur globally, from which 5.4 million are tobacco-attributed, and 4.9 million as of 2007. As of 2002, 70% of the deaths are in developing countries. As of 2017, smoking causes one in ten deaths worldwide, with half of those deaths in the US, China, India and Russia. Most smokers begin smoking during adolescence or early adulthood. Some studies also show that smoking can also be linked to various mental health complications. Smoking has elements of risk-taking and rebellion, which often appeal to young people. The presence of peers that smoke and media featuring high-status models smoking may also encourage smoking. Because teenagers are influenced more by their peers than by adults , attempts by parents, schools, and health professionals at preventing people from trying cigarettes are often unsuccessful. Children of smoking parents are more likely to smoke than children with non-smoking parents. Children of parents who smoke are less likely to quit smoking. One study found that parental smoking cessation

5704-644: The muscle sarcomere , with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids. Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis , which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield. Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. These methods are useful in laboratory biochemistry and cell biology , though generally not for commercial applications. Chemical synthesis

5828-516: The nucleus accumbens as a response to nicotine stimuli. Using rat studies, withdrawal after repeated exposure to nicotine results in less responsive nucleus accumbens cells, which produce dopamine responsible for reinforcement . As of 2000, smoking was practiced by around 1.22 billion people. At current rates of 'smoker replacement' and market growth, this may reach around 1.9 billion in 2025. Smoking may be up to five times more prevalent among men than women in some communities, although

5952-417: The prefrontal cortex , may also increase working memory . When tobacco is smoked, most of the nicotine is pyrolyzed. However, a dose sufficient to cause mild somatic dependency and mild to strong psychological dependency remains. There is also a formation of harmane (an MAO inhibitor ) from the acetaldehyde in tobacco smoke. This may play a role in nicotine addiction, by facilitating a dopamine release in

6076-645: The sperm of many multicellular organisms which reproduce sexually . They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport. A key question in molecular biology is how proteins evolve, i.e. how can mutations (or rather changes in amino acid sequence) lead to new structures and functions? Most amino acids in a protein can be changed without disrupting activity or function, as can be seen from numerous homologous proteins across species (as collected in specialized databases for protein families , e.g. PFAM ). In order to prevent dramatic consequences of mutations,

6200-497: The 1700s by Antoine Fourcroy and others, who often collectively called them " albumins ", or "albuminous materials" ( Eiweisskörper , in German). Gluten , for example, was first separated from wheat in published research around 1747, and later determined to exist in many plants. In 1789, Antoine Fourcroy recognized three distinct varieties of animal proteins: albumin , fibrin , and gelatin . Vegetable (plant) proteins studied in

6324-572: The 1950s, the Armour Hot Dog Company purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists; this gesture helped ribonuclease A become a major target for biochemical study for the following decades. The understanding of proteins as polypeptides , or chains of amino acids, came through the work of Franz Hofmeister and Hermann Emil Fischer in 1902. The central role of proteins as enzymes in living organisms that catalyzed reactions

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6448-511: The 1980s, tobacco companies claimed contributory negligence as the adverse health effects were previously unknown or lacked substantial credibility. Health authorities sided with these claims up until 1998, from which they reversed their position. The Tobacco Master Settlement Agreement , originally between the four largest US tobacco companies and the attorneys general of 46 states, restricted certain types of tobacco advertisement and required payments for health compensation; which later amounted to

6572-498: The 20,000 or so proteins encoded by the human genome, only 6,000 are detected in lymphoblastoid cells. Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG ( adenine – uracil – guanine )

6696-480: The Americas probably had its origins in the incense-burning ceremonies of shamans but was later adopted for pleasure or as a social tool. The smoking of tobacco and various hallucinogenic drugs was used to achieve trances and to come into contact with the spirit world. Also, to stimulate respiration, tobacco smoke enemas were used. Eastern North American tribes would carry large amounts of tobacco in pouches as

6820-519: The EC number system provides a functional classification scheme. Similarly, the gene ontology classifies both genes and proteins by their biological and biochemical function, but also by their intracellular location. Sequence similarity is used to classify proteins both in terms of evolutionary and functional similarity. This may use either whole proteins or protein domains , especially in multi-domain proteins . Protein domains allow protein classification by

6944-574: The Nazi anti-smoking campaign were silenced. As part of the Marshall Plan , the United States shipped free tobacco to Germany; with 24,000 tons in 1948 and 69,000 tons in 1949. Per capita yearly cigarette consumption in post-war Germany steadily rose from 460 in 1950 to 1,523 in 1963. By the end of the 20th century, anti-smoking campaigns in Germany were unable to exceed the effectiveness of

7068-671: The Nazi-era climax in the years 1939–41 and German tobacco health research was described by Robert N. Proctor as "muted". In 1950, Richard Doll published research in the British Medical Journal showing a close link between smoking and lung cancer . Beginning in December 1952, the magazine Reader's Digest published "Cancer by the Carton", a series of articles that linked smoking with lung cancer . In 1954,

7192-613: The Old World, tobacco came under frequent criticism from state and religious leaders. James VI and I , King of Scotland and England, produced the treatise A Counterblaste to Tobacco in 1604, and also introduced excise duty on the product. Murad IV , sultan of the Ottoman Empire 1623–40 was among the first to attempt a smoking ban by claiming it was a threat to public morals and health. The Chongzhen Emperor of China issued an edict banning smoking two years before his death and

7316-533: The US remained stable until the American Civil War in 1860s, when the primary agricultural workforce shifted from slavery to sharecropping . This, along with a change in demand, accompanied the industrialization of cigarette production as craftsman James Bonsack created a machine in 1881 to partially automate their manufacture. In 1912 and 1932 in Germany, anti-smoking groups, often associated with anti-liquor groups, first published advocacy against

7440-515: The United Kingdom are 0.2% for men who never smoked (0.4% for women), 5.5% for male former smokers (2.6% in women), 15.9% for current male smokers (9.5% for women) and 24.4% for male "heavy smokers" defined as smoking more than 25 cigarettes per day (18.5% for women). Tobacco smoke can combine with other carcinogens present within the environment in order to produce elevated degrees of lung cancer. The risk of lung cancer decreases almost from

7564-411: The United States, roughly 800,000 high school students smoke. The World Health Organization (WHO) states that "Much of the disease burden and premature mortality attributable to tobacco use disproportionately affect the poor". Of the 1.22 billion smokers, 1 billion of them live in developing or transitional economies. Rates of smoking have leveled off or declined in the developed world . In

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7688-709: The ability of many enzymes to bind and process multiple substrates . When mutations occur, the specificity of an enzyme can increase (or decrease) and thus its enzymatic activity. Thus, bacteria (or other organisms) can adapt to different food sources, including unnatural substrates such as plastic. Methods commonly used to study protein structure and function include immunohistochemistry , site-directed mutagenesis , X-ray crystallography , nuclear magnetic resonance and mass spectrometry . The activities and structures of proteins may be examined in vitro , in vivo , and in silico . In vitro studies of purified proteins in controlled environments are useful for learning how

7812-429: The active substances will be lost in the process of combustion, pyrolysis . Pipe and Cigar smoke are not inhaled because of its high alkalinity , which are irritating to the trachea and lungs. However, because of its higher alkalinity (pH 8.5) compared to cigarette smoke (pH 5.3), non-ionized nicotine is more readily absorbed through the mucous membranes in the mouth. Nicotine absorption from cigar and pipe, however,

7936-405: The addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine . Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of

8060-469: The aforementioned toxic chemicals, flavored tobacco contains flavorings which upon heating release toxic chemicals and carcinogens such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), furans , phenols , aldehydes (such as acrolein ), and acids, in addition to nitrogenous carcinogens , alcohols , and heavy metals , all of which are dangerous to human health. A comparison of 13 common hookah flavors found that melon flavors are

8184-485: The age-related loss of muscle mass and strength. The smoke from tobacco elicits carcinogenic effects on the tissues of the body that are exposed to the smoke. Regular cigar smoking is known to carry serious health risks , including increased risk of developing various types and subtypes of cancers , respiratory diseases , cardiovascular diseases , cerebrovascular diseases , periodontal diseases , teeth decay and loss , and malignant diseases . Tobacco smoke

8308-638: The agricultural product began to be cultivated in Mesoamerica and South America; consumption later evolved into burning the plant substance either by accident or with intent of exploring other means of consumption. The practice worked its way into shamanistic rituals. Many ancient civilizations – such as the Babylonians , the Indians, and the Chinese – burnt incense during religious rituals. Smoking in

8432-607: The alpha carbons are roughly coplanar . The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone. The end with a free amino group is known as the N-terminus or amino terminus, whereas the end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus (the sequence of the protein is written from N-terminus to C-terminus, from left to right). The words protein , polypeptide, and peptide are

8556-531: The amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity. The amino acids in a polypeptide chain are linked by peptide bonds . Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone. The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that

8680-574: The binding of a substrate molecule to an enzyme's active site , or the physical region of the protein that participates in chemical catalysis. In solution, proteins also undergo variation in structure through thermal vibration and the collision with other molecules. Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins , fibrous proteins , and membrane proteins . Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen ,

8804-570: The body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin , which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom . Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play

8928-558: The cell is as enzymes , which catalyse chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism , as well as manipulating DNA in processes such as DNA replication , DNA repair , and transcription . Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification. About 4,000 reactions are known to be catalysed by enzymes. The rate acceleration conferred by enzymatic catalysis

9052-436: The cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell. Antibodies are protein components of an adaptive immune system whose main function is to bind antigens , or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in

9176-752: The cell's machinery through the process of protein turnover . A protein's lifespan is measured in terms of its half-life and covers a wide range. They can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal or misfolded proteins are degraded more rapidly either due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids , proteins are essential parts of organisms and participate in virtually every process within cells . Many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism . Proteins also have structural or mechanical functions, such as actin and myosin in muscle and

9300-450: The cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions. Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins ; for example, collagen and elastin are critical components of connective tissue such as cartilage , and keratin

9424-446: The central nervous system and at the nerve-muscle junction of skeletal muscles; whose activity increases heart rate, alertness, and faster reaction times. Nicotine acetylcholine stimulation is not directly addictive. However, since dopamine-releasing neurons are abundant on nicotine receptors, dopamine is released; and, in the nucleus accumbens , dopamine is associated with motivation causing reinforcing behavior. Dopamine increase, in

9548-621: The chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure: Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as " conformations ", and transitions between them are called conformational changes. Such changes are often induced by

9672-441: The chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA , most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. The set of proteins expressed in

9796-490: The construction of enormously complex signaling networks. As interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types. The best-known role of proteins in

9920-583: The consumption of tobacco in the journal Der Tabakgegner (The Tobacco Opponent). In 1929, Fritz Lickint of Dresden, Germany, published a paper containing formal statistical evidence of a lung cancer–tobacco link. During the Great Depression Adolf Hitler condemned his earlier smoking habit as a waste of money, and later with stronger assertions. This movement was further strengthened with Nazi reproductive policy as women who smoked were viewed as unsuitable to be wives and mothers in

10044-408: The derivative unit kilodalton (kDa). The average size of a protein increases from Archaea to Bacteria to Eukaryote (283, 311, 438 residues and 31, 34, 49 kDa respectively) due to a bigger number of protein domains constituting proteins in higher organisms. For instance, yeast proteins are on average 466 amino acids long and 53 kDa in mass. The largest known proteins are the titins , a component of

10168-459: The early stages, a combination of perceived pleasure acting as positive reinforcement and desire to respond to social peer pressure may offset the unpleasant symptoms of initial use, which typically include nausea and coughing. After an individual has smoked for some years, the avoidance of nicotine withdrawal symptoms and negative reinforcement become the key motivations to continue. Smoking's history dates back to as early as 5000–3000 BC, when

10292-451: The erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed by Mulder's associate Berzelius; protein is derived from the Greek word πρώτειος ( proteios ), meaning "primary", "in the lead", or "standing in front", + -in . Mulder went on to identify the products of protein degradation such as

10416-403: The first day someone quits smoking and it drops by 50% after 10 years of smoking cessation. Healthy cells that have escaped mutations grow and replace the damaged ones in the lungs. In the research dated December 2019, 40% of cells in former smokers looked like those of people who had never smoked. Rates of smoking have generally leveled-off or declined in the developed world. Smoking rates in

10540-573: The form of smoking. The gender gap tends to be less pronounced in lower age groups. According to the World Health Organization , 8 million annual deaths are caused by tobacco smoking. Many smokers begin during adolescence or early adulthood. A 2009 study of first smoking experiences of seventh-grade students found out that the most common factor leading students to smoke is cigarette advertisements. Smoking by parents, siblings and friends also encourages students to smoke. During

10664-501: The fresh leaves of plants in the genus Nicotiana . The genus contains several species, of which Nicotiana tabacum is the most commonly grown. Nicotiana rustica follows second, containing higher concentrations of nicotine. The leaves are harvested and cured to allow the slow oxidation and degradation of carotenoids in tobacco leaf. This produces certain compounds in the tobacco leaves which can be attributed to sweet hay, tea, rose oil, or fruity aromatic flavors. Before packaging,

10788-515: The gender gap usually declines with younger age. In some developed countries smoking rates for men have peaked and begun to decline, while for women they continue to climb. As of 2002, about twenty percent of young teenagers (13–15) smoked worldwide. 80,000 to 100,000 children begin smoking every day, roughly half of whom live in Asia. Half of those who begin smoking in adolescent years are projected to go on to smoke for 15 to 20 years. As of 2019 in

10912-443: The heart and lungs, with smoking being a major risk factor for heart attacks , strokes , chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and emphysema . Smoking tobacco causes various types and subtypes of cancers (particularly lung cancer , cancers of the oropharynx , larynx , and mouth , esophageal and pancreatic cancer ). Using tobacco, especially together with alcohol ,

11036-735: The largest civil settlement in United States history. Social campaigns have been instituted in many places to discourage smoking, such as Canada's National Non-Smoking Week . From 1965 to 2006, rates of smoking in the United States declined from 42% to 20.8%. The majority of those who quit were professional, affluent men. Although the per-capita number of smokers decreased, the average number of cigarettes consumed per person per day increased from 22 in 1954 to 30 in 1978. This paradoxical event suggests that those who quit smoked less, while those who continued to smoke moved to smoke more light cigarettes. The trend has been paralleled by many industrialized nations as rates have either leveled-off or declined. In

11160-534: The late 1700s and early 1800s included gluten , plant albumin , gliadin , and legumin . Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the Swedish chemist Jöns Jacob Berzelius in 1838. Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula , C 400 H 620 N 100 O 120 P 1 S 1 . He came to

11284-408: The leaves and inhaling the vaporized gas that results. This quickly and effectively delivers substances into the bloodstream by absorption through the alveoli in the lungs. The lungs contain some 300 million alveoli, which amounts to a surface area of over 70 m (about the size of a tennis court). This method is not completely efficient as not all of the smoke will be inhaled, and some amount of

11408-478: The major component of connective tissue, or keratin , the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane . A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration , are called dehydrons . Many proteins are composed of several protein domains , i.e. segments of

11532-443: The mature mRNA, which is then used as a template for protein synthesis by the ribosome . In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid . In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm , where protein synthesis then takes place. The rate of protein synthesis

11656-405: The membranes of specialized B cells known as plasma cells . Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high. Many ligand transport proteins bind particular small biomolecules and transport them to other locations in

11780-727: The most dangerous, with their smoke containing four classes of hazards in high concentrations. The World Health Organization estimates that tobacco caused 8 million deaths in 2004 and 100 million deaths over the course of the 20th century. Similarly, the United States Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide." Although 70% of smokers state their intention to quit only 3–5% are actually successful in doing so. The probabilities of death from lung cancer before age 75 in

11904-511: The most significant of which is the addictive psychostimulant drug nicotine (a compound naturally found in tobacco), is absorbed through the alveoli in the lungs or the oral mucosa . Many substances in cigarette smoke, chiefly nicotine, trigger chemical reactions in nerve endings , which heighten heart rate, alertness and reaction time, among other things. Dopamine and endorphins are released, which are often associated with pleasure, leading to addiction . German scientists identified

12028-464: The native culture, despite some continued attempts upon the parts of rulers to eliminate the practice with penalties or fines. Tobacco, both product and plant, followed the major trade routes to major ports and markets, and then on into the hinterlands. The English language term smoking appears to have entered currency in the late 18th century, before which less abbreviated descriptions of the practice such as drinking smoke were also in use. Growth in

12152-580: The new trend by enforcing a 4000% tax increase on tobacco in 1604 it was unsuccessful, as suggested by the presence of around 7,000 tobacco outlets in London by the early 17th century. From this point on for some centuries, several administrations withdrew from efforts at discouragement and instead turned tobacco trade and cultivation into sometimes lucrative government monopolies. By the mid-17th century most major civilizations had been introduced to tobacco smoking and in many cases had already assimilated it into

12276-496: The nobel prize in 1972, solidified the thermodynamic hypothesis of protein folding, according to which the folded form of a protein represents its free energy minimum. With the development of X-ray crystallography , it became possible to determine protein structures as well as their sequences. The first protein structures to be solved were hemoglobin by Max Perutz and myoglobin by John Kendrew , in 1958. The use of computers and increasing computing power also supported

12400-500: The order of 50,000 to 1 million. By contrast, eukaryotic cells are larger and thus contain much more protein. For instance, yeast cells have been estimated to contain about 50 million proteins and human cells on the order of 1 to 3 billion. The concentration of individual protein copies ranges from a few molecules per cell up to 20 million. Not all genes coding proteins are expressed in most cells and their number depends on, for example, cell type and external stimuli. For instance, of

12524-703: The overthrow of the Ming dynasty . Later, the Manchu rulers of the Qing dynasty , would proclaim smoking "a more heinous crime than that even of neglecting archery". In Edo period Japan, some of the earliest tobacco plantations were scorned by the shogunate as being a threat to the military economy by letting valuable farmland go to waste for the use of a recreational drug instead of being used to plant food crops. Religious leaders have often been prominent among those who considered smoking immoral or outright blasphemous. In 1634,

12648-440: The physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Some proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors . Proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes . Once formed, proteins only exist for a certain period and are then degraded and recycled by

12772-745: The plasminogen activation system have been found to be highly expressed in many malignant tumors , indicating that tumors are able to hijack the system, and use it in metastasis . Thus inhibitors of the various components of the plasminogen activation system have been sought as possible anticancer drugs. uPAR has been involved in various other non-proteolytic processes related to cancer, such as cell migration , cell cycle regulation, and cell adhesion. Urokinase receptor has been shown to interact with LRP1 . Protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues . Proteins perform

12896-419: The possible glycosylation sites are used in vivo giving the protein a molecular weight of 50–60 kDA. uPAR is a part of the plasminogen activation system, which in the healthy body is involved in tissue reorganization events such as mammary gland involution and wound healing . In order to be able to reorganize tissue, the old tissue must be able to be degraded. An important mechanism in this degradation

13020-424: The process of cell signaling and signal transduction . Some proteins, such as insulin , are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues . Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on

13144-534: The protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity. The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according to their charge using electrofocusing . For natural proteins,

13268-427: The proteins in the cytoskeleton , which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses , cell adhesion , and the cell cycle . In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized . Digestion breaks the proteins down for metabolic use. Proteins have been studied and recognized since

13392-582: The same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein–protein interactions also regulate enzymatic activity, control progression through the cell cycle , and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows

13516-581: The sample, allowing scientists to obtain more information and analyze larger structures. Computational protein structure prediction of small protein structural domains has also helped researchers to approach atomic-level resolution of protein structures. As of April 2024 , the Protein Data Bank contains 181,018 X-ray, 19,809 EM and 12,697 NMR protein structures. Proteins are primarily classified by sequence and structure, although other classifications are commonly used. Especially for enzymes

13640-430: The sequencing of complex proteins. In 1999, Roger Kornberg succeeded in sequencing the highly complex structure of RNA polymerase using high intensity X-rays from synchrotrons . Since then, cryo-electron microscopy (cryo-EM) of large macromolecular assemblies has been developed. Cryo-EM uses protein samples that are frozen rather than crystals, and beams of electrons rather than X-rays. It causes less damage to

13764-481: The settlement of Jamestown, Virginia , John Rolfe was credited as the first settler to successfully raise tobacco as a cash crop. The demand quickly grew as tobacco, referred to as "brown gold", revived the Virginia joint stock company from its failed gold expeditions. In order to meet demands from the Old World, tobacco was grown in succession, quickly depleting the soil. This became a motivator to settle west into

13888-405: The substrate, and an even smaller fraction—three to four residues on average—that are directly involved in catalysis. The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site . Dirigent proteins are members of a class of proteins that dictate the stereochemistry of a compound synthesized by other enzymes. Many proteins are involved in

14012-716: The surrounding amino acids may determine the exact binding specificity). Many such motifs has been collected in the Eukaryotic Linear Motif (ELM) database. Topology of a protein describes the entanglement of the backbone and the arrangement of contacts within the folded chain. Two theoretical frameworks of knot theory and Circuit topology have been applied to characterise protein topology. Being able to describe protein topology opens up new pathways for protein engineering and pharmaceutical development, and adds to our understanding of protein misfolding diseases such as neuromuscular disorders and cancer. Proteins are

14136-400: The tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain . Proteins are always biosynthesized from N-terminus to C-terminus . The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass , which is normally reported in units of daltons (synonymous with atomic mass units ), or

14260-472: The tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10 M) but does not bind at all to its amphibian homolog onconase (> 1 M). Extremely minor chemical changes such as

14384-479: The tobacco is often combined with other additives in order to increase the addictive potency, shift the product's pH , or improve the effects of smoke by making it more palatable. In the United States these additives are regulated to 599 substances . The product is then processed, packaged, and shipped to consumer markets. Common methods of consuming tobacco include the following: The active substances in tobacco, especially cigarettes, are administered by burning

14508-465: The unknown continent, and likewise an expansion of tobacco production. Frenchman Jean Nicot (from whose name the word nicotine is derived) introduced tobacco to France in 1560, and tobacco then spread to England. The first report of a smoking Englishman is of a sailor in Bristol in 1556, seen "emitting smoke from his nostrils". Like tea, coffee and opium, tobacco was just one of many intoxicants that

14632-438: The waking day—with the high point usually occurring shortly after waking in the morning, and shortly before going to sleep at night. Tobacco smoking is the leading cause of preventable death and a global public health concern. There are 1.3 billion tobacco users in the world, as per latest data from WHO. One person dies every six seconds from a tobacco related disease. Tobacco use leads most commonly to diseases affecting

14756-472: Was insulin , by Frederick Sanger , in 1949. Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids , or cyclols . He won the Nobel Prize for this achievement in 1958. Christian Anfinsen 's studies of the oxidative folding process of ribonuclease A, for which he won

14880-595: Was associated with less adolescent smoking, except when the other parent currently smoked. A current study tested the relation of adolescent smoking to rules regulating where adults are allowed to smoke in the home. Results showed that restrictive home smoking policies were associated with lower likelihood of trying smoking for both middle and high school students. Behavioural research generally indicates that teenagers begin their smoking habits due to peer pressure, and cultural influence portrayed by friends. However, one study found that direct pressure to smoke cigarettes played

15004-581: Was not fully appreciated until 1926, when James B. Sumner showed that the enzyme urease was in fact a protein. Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding , an idea first put forth by William Astbury in 1933. Later work by Walter Kauzmann on denaturation , based partly on previous studies by Kaj Linderstrøm-Lang , contributed an understanding of protein folding and structure mediated by hydrophobic interactions . The first protein to have its amino acid chain sequenced

15128-481: Was originally used as a form of medicine. Tobacco was introduced around 1600 by French merchants in what today is modern-day Gambia and Senegal. At the same time, caravans from Morocco brought tobacco to the areas around Timbuktu , and the Portuguese brought the commodity (and the plant) to southern Africa, establishing the popularity of tobacco throughout all of Africa by the 1650s. Soon after its introduction to

15252-428: Was significantly associated with smoking behavior across all age and gender cohorts, but that intrapersonal factors were significantly more important to the smoking behavior of 12- to 13-year-old girls than same-age boys. Within the 14- to 15-year-old age group, one peer pressure variable emerged as a significantly more important predictor of girls' than boys' smoking. It is debated whether peer pressure or self-selection

15376-422: Was used for earache and toothache and occasionally as a poultice . Smoking was said by the desert Indians to be a cure for colds, especially if the tobacco was mixed with the leaves of the small Desert sage , Salvia dorrii , or the root of Indian balsam or cough root , Leptotaenia multifida , the addition of which was thought to be particularly good for asthma and tuberculosis . In 1612, six years after

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