Food and Drug Administration
The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements and over-the-counter pharmaceutical drugs, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices, animal foods & feed and veterinary products; as of 2017, 3/4th of the FDA budget is paid by people who consume pharmaceutical products, due to the Prescription Drug User Fee Act. The FDA was empowered by the United States Congress to enforce the Federal Food and Cosmetic Act, which serves as the primary focus for the Agency; these include regulating lasers, cellular phones and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate.
The Commissioner reports to the Secretary of Human Services. Scott Gottlieb, M. D. is the current commissioner, who took over in May 2017. The FDA has its headquarters in Maryland; the agency has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, Puerto Rico. In 2008, the FDA began to post employees to foreign countries, including China, Costa Rica, Chile and the United Kingdom. In recent years, the agency began undertaking a large-scale effort to consolidate its 25 operations in the Washington metropolitan area, moving from its main headquarters in Rockville and several fragmented office buildings to the former site of the Naval Ordnance Laboratory in the White Oak area of Silver Spring, Maryland; the site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak. The first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the naval facility was kept.
All other buildings are new construction. The project is slated to be completed by 2021, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. area as part of the Headquarters divisions, two offices – the Office of Regulatory Affairs and the Office of Criminal Investigations – are field offices with a workforce spread across the country. The Office of Regulatory Affairs is considered the "eyes and ears" of the agency, conducting the vast majority of the FDA's work in the field. Consumer Safety Officers, more called Investigators, are the individuals who inspect production and warehousing facilities, investigate complaints, illnesses, or outbreaks, review documentation in the case of medical devices, biological products, other items where it may be difficult to conduct a physical examination or take a physical sample of the product; the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based on the geographic divisions of the federal court system.
Each district comprises a main district office and a number of Resident Posts, which are FDA remote offices that serve a particular geographic area. ORA includes the Agency's network of regulatory laboratories, which analyze any physical samples taken. Though samples are food-related, some laboratories are equipped to analyze drugs and radiation-emitting devices; the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, don't focus on technical aspects of the regulated industries. OCI agents pursue and develop cases where individuals and companies have committed criminal actions, such as fraudulent claims, or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI pursues cases involving Title 18 violations, in addition to prohibited acts as defined in Chapter III of the FD&C Act. OCI Special Agents come from other criminal investigations backgrounds, work with the Federal Bureau of Investigation, Assistant Attorney General, Interpol.
OCI receives cases from a variety of sources—including ORA, local agencies, the FBI—and works with ORA Investigators to help develop the technical and science-based aspects of a case. OCI is a smaller branch; the FDA works with other federal agencies, including the Department of Agriculture, Drug Enforcement Administration and Border Protection, Consumer Product Safety Commission. Local and state government agencies work with the FDA to provide regulatory inspections and enforcement action; the FDA regulates more than US$2.4 trillion worth of consumer goods, about 25% of consumer expenditures in the United States. This includes $466 billion in food sales, $275 billion in drugs, $60 billion in cosmetics and $18 billion in vitamin supplements. Much of these expenditures are for goods imported into the United States; the FDA's federal budget request for fiscal year 2012 totaled $4.36 billion, while the proposed 2014 budget is $4.7 billion. About $2 billion of this budget is generated by user fees.
Pharmaceutical firms pay th
FooDB is a available, open-access database containing chemical composition data on common, unprocessed foods. It contains extensive data on flavour and aroma constituents, food additives as well as positive and negative health effects associated with food constituents; the database contains information on more than 28,000 chemicals found in more than 1000 raw or unprocessed food products. The data in FooDB was collected from many sources including textbooks, scientific journals, on-line food composition or nutrient databases and aroma databases and various on-line metabolomic databases; this literature-derived information has been combined with experimentally derived data measured on thousands of compounds from more than 40 common food products through the Alberta Food Metabolome Project, led by Dr. David Wishart of the University of Alberta. Users are able to browse through the FooDB data by food source, descriptors or function. Chemical structures and molecular weights for compounds in FooDB may be searched via a specialized chemical structure search utility.
Users are able to view the content of FooDB using two different “Viewing” options: FoodView, which lists foods by their chemical compounds, or ChemView, which lists chemicals by their food sources. Knowledge about the precise chemical composition of foods can be used to guide public health policies, assist food companies with improved food labelling, help dieticians prepare better dietary plans, support nutraceutical companies with their submissions of health claims and guide consumer choices with regard to food purchases. Human Metabolome Database DrugBank Food Food composition data Food composition databases Foodb website
A nutraceutical is a pharmaceutical- and standardized nutrient. In the US, "nutraceuticals" do not exist as a regulatory category. Nutraceuticals are treated differently in different jurisdictions. Under Canadian law, a nutraceutical can either be marketed as a drug; the term "nutraceutical" is not defined by US law. Depending on its ingredients and the claims with which it is marketed, a product is regulated as a drug, dietary supplement, food ingredient, or food. In the global market, there are significant product quality issues. Nutraceuticals from the international market may claim to use organic or exotic ingredients, yet the lack of regulation may compromise the safety and effectiveness of products. Companies looking to create a wide profit margin may create unregulated products overseas with low-quality or ineffective ingredients. A market research report produced in 2018 projected that the worldwide nutraceuticals market would account for over US$80,700 million in 2019, defining that market as "Dietary Supplements, Functional Foods & Beverages".
Nutraceuticals are products derived from food sources that are purported to provide extra health benefits, in addition to the basic nutritional value found in foods. Depending on the jurisdiction, products may claim to prevent chronic diseases, improve health, delay the aging process, increase life expectancy, or support the structure or function of the body. In the United States, the Dietary Supplement Health and Education Act of 1994 defined the term: “A dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet; the "dietary ingredients" in these products may include: vitamins, herbs or other botanicals, amino acids, substances such as enzymes, organ tissues and metabolites. Dietary supplements can be extracts or concentrates, may be found in many forms such as tablets, softgels, liquids, or powders.”Dietary supplements do not have to be approved by the U. S. Food and Drug Administration before marketing, but companies must register their manufacturing facilities with the FDA and follow current good manufacturing practices.
With a few well-defined exceptions, dietary supplements may only be marketed to support the structure or function of the body, may not claim to treat a disease or condition, must include a label that says: “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, cure, or prevent any disease.” The exceptions are when the FDA has approved a health claim. In those situations the FDA stipulates the exact wording allowed. Functional foods are fortified or enriched during processing and marketed as providing some benefit to consumers. Sometimes, additional complementary nutrients are added, such as vitamin D. Health Canada defines functional foods as “ordinary food that has components or ingredients added to give it a specific medical or physiological benefit, other than a purely nutritional effect.” In Japan, all functional foods must meet three established requirements: foods should be present in their occurring form, rather than a capsule, tablet, or powder.
The word "nutraceutical" is a portmanteau of the words "nutrition" and "pharmaceutical", coined in 1989 by Stephen L. DeFelice and chairman of the Foundation of Innovation Medicine. Indians, Egyptians and Sumerians are just a few civilizations that have used food as medicine. “Let food be thy medicine.” Is a common misquotation attributed to Hippocrates, considered by some to be the father of Western medicine. The modern nutraceutical market began to develop in Japan during the 1980s. In contrast to the natural herbs and spices used as folk medicine for centuries throughout Asia, the nutraceutical industry has grown alongside the expansion and exploration of modern technology. Health claims on food labels Cosmeceutical for cosmetic products with quasi-medicinal claims BooksPathak, Y. V.. Handbook of Nutraceuticals: Ingredients and Applications. CRC Press. ISBN 978-1-4200-8221-0 Shahidi, F. / Naczk, M.. Phenolics in Food and Nutraceuticals. CRC Press. ISBN 978-1-58716-138-4 Shahidi, F. / Weerasinghe, D.
K.. Nutraceutical Beverages: Chemistry and Health Effects. American Chemical Society. ISBN 978-0-8412-3823-7Review articles on possible health benefitsAggarwal, B. B. et al. “Molecular Targets of Nutraceuticals Derived from Dietary Spices: Potential Role in Suppression of Inflammation and Tumorigenesis”, Experimental Biology and Medicine,234:825-849. Gupta, S. C. et al. ” Regulation of survival, invasion and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals“, Cancer Metastasis Reviews,29:405-434. Kannappan, R. et al. “Neuroprotection by Spice-Derived Nutraceuticals: You Are What You Eat!”, Molecular Neurobiology,44:142-159. Agriculture and Agri-Food Canada, Functional Foods and Nutraceuticals, 2007 US FDA/CFSAN - Dietary Supplements
Peptides are short chains of amino acid monomers linked by peptide bonds. The covalent chemical bonds are formed when the carboxyl group of one amino acid reacts with the amino group of another; the shortest peptides are dipeptides, consisting of 2 amino acids joined by a single peptide bond, followed by tripeptides, etc. A polypeptide is a long and unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids and polysaccharides, etc. Peptides are distinguished from proteins on the basis of size, as an arbitrary benchmark can be understood to contain 50 or fewer amino acids. Proteins consist of one or more polypeptides arranged in a biologically functional way bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule, or to complex macromolecular assemblies. While aspects of the lab techniques applied to peptides versus polypeptides and proteins differ, the size boundaries that distinguish peptides from polypeptides and proteins are not absolute: long peptides such as amyloid beta have been referred to as proteins, smaller proteins like insulin have been considered peptides.
Amino acids that have been incorporated into peptides are termed "residues" due to the release of either a hydrogen ion from the amine end or a hydroxyl ion from the carboxyl end, or both, as a water molecule is released during formation of each amide bond. All peptides except cyclic peptides have an N-terminal and C-terminal residue at the end of the peptide. Many kinds of peptides are known, they have been categorized according to their sources and function. According to the Handbook of Biologically Active Peptides, some groups of peptides include plant peptides, bacterial/antibiotic peptides, fungal peptides, invertebrate peptides, amphibian/skin peptides, venom peptides, cancer/anticancer peptides, vaccine peptides, immune/inflammatory peptides, brain peptides, endocrine peptides, ingestive peptides, gastrointestinal peptides, cardiovascular peptides, renal peptides, respiratory peptides, opiate peptides, neurotrophic peptides, blood–brain peptides; some ribosomal peptides are subject to proteolysis.
These function in higher organisms, as hormones and signaling molecules. Some organisms produce peptides as antibiotics, such as microcins. Peptides have posttranslational modifications such as phosphorylation, sulfonation, palmitoylation and disulfide formation. In general, peptides are linear. More exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom. Nonribosomal peptides are assembled by enzymes, not the ribosome. A common non-ribosomal peptide is glutathione, a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in unicellular organisms and fungi and are synthesized by modular enzyme complexes called nonribosomal peptide synthetases; these complexes are laid out in a similar fashion, they can contain many different modules to perform a diverse set of chemical manipulations on the developing product. These peptides are cyclic and can have complex cyclic structures, although linear nonribosomal peptides are common.
Since the system is related to the machinery for building fatty acids and polyketides, hybrid compounds are found. The presence of oxazoles or thiazoles indicates that the compound was synthesized in this fashion. Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein; these are the products of enzymatic degradation performed in the laboratory on a controlled sample, but can be forensic or paleontological samples that have been degraded by natural effects. Use of peptides received prominence in molecular biology for several reasons; the first is that peptides allow the creation of peptide antibodies in animals without the need of purifying the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest; these will be used to make antibodies in a rabbit or mouse against the protein. Another reason is that techniques such as mass spectrometry enable the identification of proteins based on the peptide masses and sequence that result from their fragmentation.
Peptides have been used in the study of protein structure and function. For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur- see the page on Protein tags. Inhibitory peptides are used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases. For example, one of the most promising application is through peptides that target LHRH; these particular peptides act as an agonist, meaning that they bind to a cell in a way that regulates LHRH receptors. The process of inhibiting the cell receptors suggests that peptides could be beneficial in treating prostate cancer, but additional investigations and experiments are required before their cancer-fighting attributes can be considered definitive; the peptide families in this section are ribosomal peptides with hormonal activity. All of these peptides are synthesized by cells as longer "propeptides" or "proproteins" and truncated prior to exiting the cell.
They are released into the bloodstream. Magainin family Cecropin famil
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 bioinformatics, BLAST is an algorithm for comparing primary biological sequence information, such as the amino-acid sequences of proteins or the nucleotides of DNA and/or RNA sequences. A BLAST search enables a researcher to compare a query sequence with a library or database of sequences, identify library sequences that resemble the query sequence above a certain threshold. Different types of BLASTs are available according to the query sequences. For example, following the discovery of a unknown gene in the mouse, a scientist will perform a BLAST search of the human genome to see if humans carry a similar gene; the BLAST algorithm and program were designed by Stephen Altschul, Warren Gish, Webb Miller, Eugene Myers, David J. Lipman at the National Institutes of Health and was published in the Journal of Molecular Biology in 1990 and cited over 75,000 times. BLAST is one of the most used bioinformatics programs for sequence searching, it addresses a fundamental problem in bioinformatics research.
The heuristic algorithm it uses is much faster than other approaches, such as calculating an optimal alignment. This emphasis on speed is vital to making the algorithm practical on the huge genome databases available, although subsequent algorithms can be faster. Before BLAST, FASTA was developed by David J. Lipman and William R. Pearson in 1985. Before fast algorithms such as BLAST and FASTA were developed, doing database searches for protein or nucleic sequences was time consuming because a full alignment procedure was used. While BLAST is faster than any Smith-Waterman implementation for most cases, it cannot "guarantee the optimal alignments of the query and database sequences" as Smith-Waterman algorithm does; the optimality of Smith-Waterman "ensured the best performance on accuracy and the most precise results" at the expense of time and computer power. BLAST is more time-efficient than FASTA by searching only for the more significant patterns in the sequences, yet with comparative sensitivity.
This could be further realized by understanding the algorithm of BLAST introduced below. Examples of other questions that researchers use BLAST to answer are: Which bacterial species have a protein, related in lineage to a certain protein with known amino-acid sequence What other genes encode proteins that exhibit structures or motifs such as ones that have just been determinedBLAST is often used as part of other algorithms that require approximate sequence matching; the BLAST algorithm and the computer program that implements it were developed by Stephen Altschul, Warren Gish, David Lipman at the U. S. National Center for Biotechnology Information, Webb Miller at the Pennsylvania State University, Gene Myers at the University of Arizona, it is available on the web on the NCBI website. Alternative implementations include AB-BLAST, FSA-BLAST, ScalaBLAST; the original paper by Altschul, et al. was the most cited paper published in the 1990s. Input sequences and weight matrix. BLAST output can be delivered in a variety of formats.
These formats include HTML, plain text, XML formatting. For NCBI's web-page, the default format for output is HTML; when performing a BLAST on NCBI, the results are given in a graphical format showing the hits found, a table showing sequence identifiers for the hits with scoring related data, as well as alignments for the sequence of interest and the hits received with corresponding BLAST scores for these. The easiest to read and most informative of these is the table. If one is attempting to search for a proprietary sequence or one, unavailable in databases available to the general public through sources such as NCBI, there is a BLAST program available for download to any computer, at no cost; this can be found at BLAST+ executables. There are commercial programs available for purchase. Databases can be found from the NCBI site, as well as from Index of BLAST databases. Using a heuristic method, BLAST finds similar sequences, by locating short matches between the two sequences; this process of finding similar sequences is called seeding.
It is after this first match. While attempting to find similarity in sequences, sets of common letters, known as words, are important. For example, suppose that the sequence contains the following stretch of letters, GLKFA. If a BLAST was being conducted under normal conditions, the word size would be 3 letters. In this case, using the given stretch of letters, the searched words would be GLK, LKF, KFA; the heuristic algorithm of BLAST locates all common three-letter words between the sequence of interest and the hit sequence or sequences from the database. This result will be used to build an alignment. After making words for the sequence of interest, the rest of the words are assembled; these words must satisfy a requirement of having a score of at least the threshold T, when compared by using a scoring matrix. One used scoring matrix for BLAST searches is BLOSUM62, although the optimal scoring matrix depends on sequence similarity. Once both words and neighborhood words are assembled and compiled, they are compared to the sequences in the database in order to find matches.
The threshold score. Once seeding has been conducted, the alignment, only 3 residues long, is extended in both directions by the algorithm used by BLAST; each extension impacts the score of the alignment by either increasing
Toxin and Toxin-Target Database
The Toxin and Toxin-Target Database known as the Toxic Exposome Database, is a accessible online database of common substances that are toxic to humans, along with their protein, DNA or organ targets. The database houses nearly 3,700 toxic compounds or poisons described by nearly 42,000 synonyms; this list includes various groups of toxins, including common pollutants, drugs, food toxins and industrial/workplace toxins, cigarette toxins, uremic toxins. These toxic substances are linked to 2,086 corresponding protein/DNA target records. In total there are 42,433 toxic substance-toxin target associations; each toxic compound record in T3DB contains nearly 100 data fields and holds information such as chemical properties and descriptors, mechanisms of action, toxicity or lethal dose values and cellular interactions, medical information, NMR an MS spectra, up- and down-regulated genes. This information has been extracted from over 18,000 sources, which include other databases, government documents and scientific literature.
The primary focus of the T3DB is on providing mechanisms of toxicity and identifying target proteins for common toxic substances. While a number of other toxic compound databases do exist, their emphasis is on covering large numbers of chemical compounds that are never seen outside a chemical laboratory. T3DB attempts to capture data on only those toxic substances that are abundant or in widespread use and have been detected or measured in humans. T3DB is searchable and supports extensive text, chemical structure, relational query and spectral searches, it is both modelled after and linked to the Human Metabolome Database and DrugBank. Potential applications of T3DB include metabolomics and environmental exposure studies, toxic compound metabolism prediction, toxin/drug interaction prediction, general toxic substance awareness. All data in T3DB is derived from a non-proprietary source, it is accessible and available to anyone. In addition, nearly every data item is traceable and explicitly referenced to the original source.
T3DB data is available through downloads. Poison Toxin List of hazardous substances List of biological databases KEGG HMDB SMPDB