Glycine is an amino acid that has a single hydrogen atom as its side chain. It is the simplest amino acid, with the chemical formula NH2‐CH2‐COOH. Glycine is one of the proteinogenic amino acids, it is encoded by all the codons starting with GG. Glycine is known as a "helix breaker", due to its ability to act as a hinge in the secondary structure of proteins. Glycine is a sweet-tasting crystalline solid, it is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom; the acyl radical is glycyl. Glycine was discovered in 1820 by the French chemist Henri Braconnot when he hydrolyzed gelatin by boiling it with sulfuric acid, he called it "sugar of gelatin", but the French chemist Jean-Baptiste Boussingault showed that it contained nitrogen. The American scientist Eben Norton Horsford a student of the German chemist Justus von Liebig, proposed the name "glycocoll"; the name comes from the Greek word γλυκύς "sweet tasting".
In 1858, the French chemist Auguste Cahours determined. Although glycine can be isolated from hydrolyzed protein, this is not used for industrial production, as it can be manufactured more conveniently by chemical synthesis; the two main processes are amination of chloroacetic acid with ammonia, giving glycine and ammonium chloride, the Strecker amino acid synthesis, the main synthetic method in the United States and Japan. About 15 thousand tonnes are produced annually in this way. Glycine is cogenerated as an impurity in the synthesis of EDTA, arising from reactions of the ammonia coproduct. In aqueous solution, glycine itself is amphoteric: at low pH the molecule can be protonated with a pKa of about 2.4 and at high pH it loses a proton with a pKa of about 9.6. Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, in turn derived from 3-phosphoglycerate, but the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.
In most organisms, the enzyme serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate: serine + tetrahydrofolate → glycine + N5,N10-Methylene tetrahydrofolate + H2OIn the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase. This conversion is reversible: CO2 + NH+4 + N5,N10-Methylene tetrahydrofolate + NADH + H+ ⇌ Glycine + tetrahydrofolate + NAD+ Glycine is degraded via three pathways; the predominant pathway in animals and plants is the reverse of the glycine synthase pathway mentioned above. In this context, the enzyme system involved is called the glycine cleavage system: Glycine + tetrahydrofolate + NAD+ ⇌ CO2 + NH+4 + N5,N10-Methylene tetrahydrofolate + NADH + H+In the second pathway, glycine is degraded in two steps; the first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is converted to pyruvate by serine dehydratase. In the third pathway of glycine degradation, glycine is converted to glyoxylate by D-amino acid oxidase.
Glyoxylate is oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction. The half-life of glycine and its elimination from the body varies based on dose. In one study, the half-life varied between 4.0 hours. The principal function of glycine is as a precursor to proteins. Most proteins incorporate only small quantities of glycine, a notable exception being collagen, which contains about 35% glycine due to its periodically repeated role in the formation of collagen's helix structure in conjunction with hydroxyproline. In the genetic code, glycine is coded by all codons starting with GG, namely GGU, GGC, GGA and GGG. In higher eukaryotes, δ-aminolevulinic acid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA by the enzyme ALA synthase. Glycine provides the central C2N subunit of all purines. Glycine is an inhibitory neurotransmitter in the central nervous system in the spinal cord and retina; when glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential.
Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the glutamatergic receptors which are excitatory; the LD50 of glycine is 7930 mg/kg in rats, it causes death by hyperexcitability. In the US, glycine is sold in two grades: United States Pharmacopeia, technical grade. USP grade sales account for 80 to 85 percent of the U. S. market for glycine. If purity greater than the USP standard is needed, for example for intravenous injections, a more expensive pharmaceutical grade glycine can be used. Technical grade glycine, which may or may not meet USP grade standards, is sold at a lower price for use in industrial applications, e.g. as an agent in metal complexing and finishing. USP glycine has a wide variety of uses, including as an additive in pet food and animal feed, in foods and pharmaceuticals as a sweetener/taste enhancer, or as a component of food supplements and protein drinks.
Two glycine molecules in a dipeptide form are referred to as a diglycinate. Because they use a different s
Phenylalanine is an essential α-amino acid with the formula C9H11NO2. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine; this essential amino acid is classified as neutral, nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins, coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine and epinephrine, the skin pigment melanin, it is encoded by the codons UUU and UUC. Phenylalanine is found in the breast milk of mammals, it is used in the manufacture of food and drink products and sold as a nutritional supplement for its reputed analgesic and antidepressant effects. It is a direct precursor to the neuromodulator phenethylamine, a used dietary supplement; as an essential amino acid, phenylalanine is not synthesized de novo in humans and other animals, who must ingest phenylalanine or phenylalanine-containing proteins.
The first description of phenylalanine was made in 1879, when Schulze and Barbieri identified a compound with the empirical formula, C9H11NO2, in yellow lupine seedlings. In 1882, Erlenmeyer and Lipp first synthesized phenylalanine from phenylacetaldehyde, hydrogen cyanide, ammonia; the genetic codon for phenylalanine was first discovered by J. Heinrich Matthaei and Marshall W. Nirenberg in 1961, they showed that by using mRNA to insert multiple uracil repeats into the genome of the bacterium E. coli, they could cause the bacterium to produce a polypeptide consisting of repeated phenylalanine amino acids. This discovery helped to establish the nature of the coding relationship that links information stored in genomic nucleic acid with protein expression in the living cell. Good sources of phenylalanine are eggs, liver, beef and soybeans; the Food and Nutrition Board of the U. S. Institute of Medicine set Recommended Dietary Allowances for essential amino acids in 2002. For phenylalanine plus tyrosine, for adults 19 years and older, 33 mg/kg body weight/day.
L-Phenylalanine is biologically converted into L-tyrosine, another one of the DNA-encoded amino acids. L-tyrosine in turn is converted into L-DOPA, further converted into dopamine and epinephrine; the latter three are known as the catecholamines. Phenylalanine uses the same active transport channel as tryptophan to cross the blood–brain barrier. In excessive quantities, supplementation can interfere with the production of serotonin and other aromatic amino acids as well as nitric oxide due to the overuse of the associated cofactors, iron or tetrahydrobiopterin; the corresponding enzymes in for those compounds are the aromatic amino acid hydroxylase family and nitric oxide synthase. Phenylalanine is the starting compound used in the synthesis of flavonoids. Lignan is derived from tyrosine. Phenylalanine is converted to cinnamic acid by the enzyme phenylalanine ammonia-lyase; the genetic disorder phenylketonuria is the inability to metabolize phenylalanine because of a lack of the enzyme phenylalanine hydroxylase.
Individuals with this disorder are known as "phenylketonurics" and must regulate their intake of phenylalanine. Phenylketonurics use blood tests to monitor the amount of phenylalanine in their blood. Lab results may report phenylalanine levels using either mg/dL and μmol/L. One mg/dL of phenylalanine is equivalent to 60 μmol/L. A "variant form" of phenylketonuria called hyperphenylalaninemia is caused by the inability to synthesize a cofactor called tetrahydrobiopterin, which can be supplemented. Pregnant women with hyperphenylalaninemia may show similar symptoms of the disorder, but these indicators will disappear at the end of gestation. Pregnant women with PKU must control their blood phenylalanine levels if the fetus is heterozygous for the defective gene because the fetus could be adversely affected due to hepatic immaturity. A non-food source of phenylalanine is the artificial sweetener aspartame; this compound is metabolized by the body into several chemical byproducts including phenylalanine.
The breakdown problems phenylketonurics have with the buildup of phenylalanine in the body occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in Australia, the U. S. and Canada that contain aspartame must be labeled: "Phenylketonurics: Contains phenylalanine." In the UK, foods containing aspartame must carry ingredient panels that refer to the presence of "aspartame or E951" and they must be labeled with a warning "Contains a source of phenylalanine." In Brazil, the label "Contém Fenilalanina" is mandatory in products which contain it. These warnings are placed to help individuals avoid such foods. Geneticists sequenced the genome of macaques in 2007, their investigations found "some instances where the normal form of the macaque protein looked like the diseased human protein" including markers for PKU. The stereoisomer D-phenylalanine can be produced by conventional organic synthesis, either as a single enantiomer or as a component of the racemic mixture.
It does not participate in protein biosynthesis although it is found in proteins in small amounts - aged proteins and food proteins that have been processed. The biological functions of D-amino acids remain unclear, although D-phenylalanine has pharmacological activity at niacin receptor 2. DL-Phenylalanine is marketed as a nutritional supplement for its purported analgesic and antidepressant activ
Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen and nitrogen, although other elements are found in the side chains of certain amino acids. About 500 occurring amino acids are known and can be classified in many ways, they can be classified according to the core structural functional groups' locations as alpha-, beta-, gamma- or delta- amino acids. In the form of proteins, amino acid residues form the second-largest component of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first carbon atom have particular importance, they are known as α-amino acids. They include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins.
These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, in some antibiotics. Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as "standard" amino acids; the other two are selenocysteine, pyrrolysine. Pyrrolysine and selenocysteine are encoded via variant codons. N-formylmethionine is considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids have biological functions. For example, in the human brain and gamma-amino-butyric acid are the main excitatory and inhibitory neurotransmitters. Hydroxyproline, a major component of the connective tissue collagen, is synthesised from proline. Glycine is a biosynthetic precursor to porphyrins used in red blood cells.
Carnitine is used in lipid transport. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for medical conditions. Essential amino acids may differ between species; because of their biological significance, amino acids are important in nutrition and are used in nutritional supplements, fertilizers and food technology. Industrial uses include the production of drugs, biodegradable plastics, chiral catalysts; the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus, subsequently named asparagine, the first amino acid to be discovered. Cystine was discovered in 1810, although its monomer, remained undiscovered until 1884. Glycine and leucine were discovered in 1820; the last of the 20 common amino acids to be discovered was threonine in 1935 by William Cumming Rose, who determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth.
The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it. Usage of the term "amino acid" in the English language is from 1898, while the German term, Aminosäure, was used earlier. Proteins were found to yield amino acids after enzymatic acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide". In the structure shown at the top of the page, R represents a side chain specific to each amino acid; the carbon atom next to the carboxyl group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as alpha amino acids; these include amino acids such as proline which contain secondary amines, which used to be referred to as "imino acids". The alpha amino acids are the most common form found in nature, but only when occurring in the L-isomer.
The alpha carbon is a chiral carbon atom, with the exception of glycine which has two indistinguishable hydrogen atoms on the alpha carbon. Therefore, all alpha amino acids but glycine can exist in either of two enantiomers, called L or D amino acids, which are mirror images of each other. While L-amino acids represent all of the amino acids found in proteins during translation in the ribosome, D-amin
Leucine is an essential amino acid, used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group, an α-carboxylic acid group, a side chain isobutyl group, making it a non-polar aliphatic amino acid, it is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, beans and other legumes, it is encoded by the codons UUA, UUG, CUU, CUC, CUA, CUG. Like valine and isoleucine, leucine is a branched-chain amino acid; the primary metabolic end products of leucine metabolism are acetoacetate. It is the most important ketogenic amino acid in humans.p. 101Leucine and β-hydroxy β-methylbutyric acid, a minor leucine metabolite, exhibit pharmacological activity in humans and have been demonstrated to promote protein biosynthesis via the phosphorylation of the mechanistic target of rapamycin. As a food additive, L-leucine is classified as a flavor enhancer.
The Food and Nutrition Board of the U. S. Institute of Medicine set Recommended Dietary Allowances for essential amino acids in 2002. For leucine, for adults 19 years and older, 42 mg/kg body weight/day; as a dietary supplement, leucine has been found to slow the degradation of muscle tissue by increasing the synthesis of muscle proteins in aged rats. However, results of comparative studies are conflicted. Long-term leucine supplementation does not increase muscle strength in healthy elderly men. More studies are needed, preferably ones based on an random sample of society. Factors such as lifestyle choices, gender, exercise, etc. must be factored into the analyses to isolate the effects of supplemental leucine as a standalone, or if taken with other branched chain amino acids. Until dietary supplemental leucine cannot be associated as the prime reason for muscular growth or optimal maintenance for the entire population. Both L-leucine and D-leucine protect mice against seizures. D-leucine terminates seizures in mice after the onset of seizure activity, at least as as diazepam and without sedative effects.
Decreased dietary intake of L-leucine promotes adiposity in mice. High blood levels of leucine are associated with insulin resistance in humans and rodents; this might be due to the effect of leucine to stimulate mTOR signaling. Dietary restriction of leucine and the other BCAAs can reverse diet-induced obesity in wild-type mice by increasing energy expenditure, can restrict fat mass gain of hyperphagic rats. Leucine toxicity, as seen in decompensated maple syrup urine disease, causes delirium and neurologic compromise, can be life-threatening. A high intake of leucine may cause or exacerbate symptoms of pellagra in people with low niacin status because it interferes with the conversion of L-tryptophan to niacin. Leucine at a dose exceeding 500 mg/kg/d was observed with hyperammonemia; as such, unofficially, a tolerable upper intake level for leucine in healthy adult men can be suggested at 500 mg/kg/d or 35 g/d under acute dietary conditions. Leucine is a dietary amino acid with the capacity to directly stimulate myofibrillar muscle protein synthesis.
This effect of leucine arises results from its role as an activator of the mechanistic target of rapamycin, a serine-threonine protein kinase that regulates protein biosynthesis and cell growth. The activation of mTOR by leucine is mediated through Rag GTPases, leucine binding to leucyl-tRNA synthetase, leucine binding to sestrin 2, other mechanisms. Leucine metabolism occurs in many tissues in the human body. Adipose and muscle tissue use leucine in the formation of other compounds. Combined leucine use in these two tissues is seven times greater than in the liver. In healthy individuals 60% of dietary L-leucine is metabolized after several hours, with 5% of dietary L-leucine being converted to β-hydroxy β-methylbutyric acid. Around 40% of dietary L-leucine is converted to acetyl-CoA, subsequently used in the synthesis of other compounds; the vast majority of L-leucine metabolism is catalyzed by the branched-chain amino acid aminotransferase enzyme, producing α-ketoisocaproate. Α-KIC is metabolized by the mitochondrial enzyme branched-chain α-ketoacid dehydrogenase, which converts it to isovaleryl-CoA.
Isovaleryl-CoA is subsequently metabolized by isovaleryl-CoA dehydrogenase and converted to MC-CoA, used in the synthesis of acetyl-CoA and other compounds. During biotin deficiency, HMB can be synthesized from MC-CoA via enoyl-CoA hydratase and an unknown thioesterase enzyme, which convert MC-CoA into HMB-CoA and HMB-CoA into HMB respectively. A small amount of α-KIC is metabolized in the liver by the cytosolic enzyme 4-hydroxyphenylpyruvate dioxygenase, which converts α-KIC to HMB. In healthy individuals, this minor pathway – which involves the conversion of L-leucine to α-KIC and HMB – is the predominant route of HMB synthesis. A small fraction of L-leucine metabolism – less than 5% in all tissues except the testes where it accounts for about 33% – is catalyzed by leucine aminomutase, producing β-leucine, subsequently metabolized into β-ketoisocaproate, β-ketoisocaproyl-CoA, acetyl-CoA by a series of uncharacterized enzymes; the metabolism o
Eukaryotes are organisms whose cells have a nucleus enclosed within membranes, unlike prokaryotes, which have no membrane-bound organelles. Eukaryotes belong to Eukarya, their name comes from the Greek εὖ and κάρυον. Eukaryotic cells contain other membrane-bound organelles such as mitochondria and the Golgi apparatus, in addition, some cells of plants and algae contain chloroplasts. Unlike unicellular archaea and bacteria, eukaryotes may be multicellular and include organisms consisting of many cell types forming different kinds of tissue. Animals and plants are the most familiar eukaryotes. Eukaryotes can reproduce both asexually through mitosis and sexually through meiosis and gamete fusion. In mitosis, one cell divides to produce two genetically identical cells. In meiosis, DNA replication is followed by two rounds of cell division to produce four haploid daughter cells; these act as sex cells. Each gamete has just one set of chromosomes, each a unique mix of the corresponding pair of parental chromosomes resulting from genetic recombination during meiosis.
The domain Eukaryota appears to be monophyletic, makes up one of the domains of life in the three-domain system. The two other domains and Archaea, are prokaryotes and have none of the above features. Eukaryotes represent a tiny minority of all living things. However, due to their much larger size, their collective worldwide biomass is estimated to be about equal to that of prokaryotes. Eukaryotes evolved 1.6–2.1 billion years ago, during the Proterozoic eon. The concept of the eukaryote has been attributed to the French biologist Edouard Chatton; the terms prokaryote and eukaryote were more definitively reintroduced by the Canadian microbiologist Roger Stanier and the Dutch-American microbiologist C. B. van Niel in 1962. In his 1937 work Titres et Travaux Scientifiques, Chatton had proposed the two terms, calling the bacteria prokaryotes and organisms with nuclei in their cells eukaryotes; however he mentioned this in only one paragraph, the idea was ignored until Chatton's statement was rediscovered by Stanier and van Niel.
In 1905 and 1910, the Russian biologist Konstantin Mereschkowski argued that plastids were reduced cyanobacteria in a symbiosis with a non-photosynthetic host, itself formed by symbiosis between an amoeba-like host and a bacterium-like cell that formed the nucleus. Plants had thus inherited photosynthesis from cyanobacteria. In 1967, Lynn Margulis provided microbiological evidence for endosymbiosis as the origin of chloroplasts and mitochondria in eukaryotic cells in her paper, On the origin of mitosing cells. In the 1970s, Carl Woese explored microbial phylogenetics, studying variations in 16S ribosomal RNA; this helped to uncover the origin of the eukaryotes and the symbiogenesis of two important eukaryote organelles and chloroplasts. In 1977, Woese and George Fox introduced a "third form of life", which they called the Archaebacteria. In 1979, G. W. Gould and G. J. Dring suggested that the eukaryotic cell's nucleus came from the ability of Gram-positive bacteria to form endospores. In 1987 and papers, Thomas Cavalier-Smith proposed instead that the membranes of the nucleus and endoplasmic reticulum first formed by infolding a prokaryote's plasma membrane.
In the 1990s, several other biologists proposed endosymbiotic origins for the nucleus reviving Mereschkowski's theory. Eukaryotic cells are much larger than those of prokaryotes having a volume of around 10,000 times greater than the prokaryotic cell, they have a variety of internal membrane-bound structures, called organelles, a cytoskeleton composed of microtubules and intermediate filaments, which play an important role in defining the cell's organization and shape. Eukaryotic DNA is divided into several linear bundles called chromosomes, which are separated by a microtubular spindle during nuclear division. Eukaryote cells include a variety of membrane-bound structures, collectively referred to as the endomembrane system. Simple compartments, called vesicles and vacuoles, can form by budding off other membranes. Many cells ingest food and other materials through a process of endocytosis, where the outer membrane invaginates and pinches off to form a vesicle, it is probable that most other membrane-bound organelles are derived from such vesicles.
Alternatively some products produced by the cell can leave in a vesicle through exocytosis. The nucleus is surrounded with pores that allow material to move in and out. Various tube- and sheet-like extensions of the nuclear membrane form the endoplasmic reticulum, involved in protein transport and maturation, it includes the rough endoplasmic reticulum where ribosomes are attached to synthesize proteins, which enter the interior space or lumen. Subsequently, they enter vesicles, which bud off from the smooth endoplasmic reticulum. In most eukaryotes, these protein-carrying vesicles are released and further modified in stacks of flattened vesicles, the Golgi apparatus. Vesicles may be specialized for various purposes. For instance, lysosomes contain digestive enzymes that break down most biomolecules in the cytoplasm. Peroxisomes are used to break down peroxide, otherwise toxic. Many protozoans have contractile vacuoles, which collect and expel excess water, extrusomes, which expel material used to deflect predators or capture prey.
In higher plants, most of a cell's volume is taken up by a central vacuole, whi
Glutamic acid is an α-amino acid, used by all living beings in the biosynthesis of proteins. It is non-essential in humans, it is an excitatory neurotransmitter, in fact the most abundant one, in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid in GABA-ergic neurons, it has a formula C5H9O4N. Its molecular structure could be idealized as HOOC-CH-2-COOH, with two carboxyl groups -COOH and one amino group -NH2. However, in the solid state and mildly acid water solutions, the molecule assumes an electrically neutral zwitterion structure −OOC-CH-2-COOH, it is encoded by the codons GAA or GAG. The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamate −OOC-CH-2-COO−; this form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the principal role in neural activation; this anion is responsible for the savory flavor of certain foods, used in glutamate flavorings such as MSG.
In Europe it is classified as food additive E620. In alkaline solutions the doubly negative anion −OOC-CH-2-COO− prevails; the radical corresponding to glutamate is called glutamyl. When glutamic acid is dissolved in water, the amino group may gain a proton, and/or the carboxyl groups may lose protons, depending on the acidity of the medium. In sufficiently acidic environments, the amino group gains a proton and the molecule becomes a cation with a single positive charge, HOOC-CH-2-COOH. At pH values between about 2.5 and 4.1, the carboxylic acid closer to the amine loses a proton, the acid becomes the neutral zwitterion −OOC-CH-2-COOH. This is the form of the compound in the crystalline solid state; the change in protonation state is gradual. At higher pH, the other carboxylic acid group loses its proton and the acid exists entirely as the glutamate anion −OOC-CH-2-COO−, with a single negative charge overall; the change in protonation state occurs at pH 4.07. This form with both carboxylates lacking protons is dominant in the physiological pH range.
At higher pH, the amino group loses the extra proton and the prevalent species is the doubly-negative anion −OOC-CH-2-COO−. The change in protonation state occurs at pH 9.47. The carbon atom adjacent to the amino group is chiral, so glutamic acid can exist in two optical isomers, D and L; the L form is the one most occurring in nature, but the D form occurs in some special contexts, such as the cell walls of the bacteria and the liver of mammals. Although they occur in many foods, the flavor contributions made by glutamic acid and other amino acids were only scientifically identified early in the twentieth century; the substance was discovered and identified in the year 1866, by the German chemist Karl Heinrich Ritthausen who treated wheat gluten with sulfuric acid. In 1908 Japanese researcher Kikunae Ikeda of the Tokyo Imperial University identified brown crystals left behind after the evaporation of a large amount of kombu broth as glutamic acid; these crystals, when tasted, reproduced the ineffable but undeniable flavor he detected in many foods, most in seaweed.
Professor Ikeda termed this flavor umami. He patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate. Glutamic acid is produced on the largest scale of any amino acid, with an estimated annual production of about 1.5 million tons in 2006. Chemical synthesis was supplanted by the aerobic fermentation of sugars and ammonia in the 1950s, with the organism Corynebacterium glutamicum being the most used for production. Isolation and purification can be achieved by crystallization. Glutamate is a key compound in cellular metabolism. In humans, dietary proteins are broken down by digestion into amino acids, which serve as metabolic fuel for other functional roles in the body. A key process in amino acid degradation is transamination, in which the amino group of an amino acid is transferred to an α-ketoacid catalysed by a transaminase; the reaction can be generalised as such: R1-amino acid + R2-α-ketoacid ⇌ R1-α-ketoacid + R2-amino acidA common α-keto acid is α-ketoglutarate, an intermediate in the citric acid cycle.
Transamination of α-ketoglutarate gives glutamate. The resulting α-ketoacid product is a useful one as well, which can contribute as fuel or as a substrate for further metabolism processes. Examples are as follows: Alanine + α-ketoglutarate ⇌ pyruvate + glutamateAspartate + α-ketoglutarate ⇌ oxaloacetate + glutamateBoth pyruvate and oxaloacetate are key components of cellular metabolism, contributing as substrates or intermediates in fundamental processes such as glycolysis and the citric acid cycle. Glutamate plays an important role in the body's disposal of excess or waste nitrogen. Glutamate undergoes deamination, an oxidative reaction catalysed by glutamate dehydrogenase, as follows: glutamate + H2O + NADP+ → α-ketoglutarate + NADPH + NH3 + H+Ammonia is excreted predominantly as urea, synthesised in the liver. Transamination can thus be linked to deamination allowing nitrogen from the amine groups of amino acids to be removed, via glutamate as an intermediate, excreted from the body in the form of urea.
Glutamate is a
Tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group; the word "tyrosine" is from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional side chain. While tyrosine is classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine, it is encoded by the codons UAC and UAU in messenger RNA. Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality, it occurs in proteins. It functions as a receiver of phosphate groups. Phosphorylation of the hydroxyl group can change the activity of the target protein, or may form part of a signaling cascade via SH2 domain binding. A tyrosine residue plays an important role in photosynthesis. In chloroplasts, it acts as an electron donor in the reduction of oxidized chlorophyll.
In this process, it loses the hydrogen atom of its phenolic OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese clusters; the Dietary Reference Intake for phenylalanine and tyrosine is 33 mg per kilogram of body weight, or 15 mg per pound. For a 70 kg person, this is 2310 mg. Tyrosine, which can be synthesized in the body from phenylalanine, is found in many high-protein food products such as chicken, fish, yogurt, cottage cheese, peanuts, pumpkin seeds, sesame seeds, soy products, lima beans and bananas. For example, the white of an egg has about 250 mg per egg, while lean beef/lamb/pork/salmon/chicken/turkey contains about 1000 mg per 3 ounces portion. In plants and most microorganisms, tyr is produced via prephenate, an intermediate on the shikimate pathway. Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate, transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate.
Mammals synthesize tyrosine from the essential amino acid phenylalanine, derived from food. The conversion of phe to tyr is catalyzed by a monooxygenase; this enzyme catalyzes the reaction causing the addition of a hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine. Some of the tyrosine residues can be tagged with a phosphate group by protein kinases. In its phosphorylated form, tyrosine is called phosphotyrosine. Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase. Like the phosphotyrosine antibodies mentioned above, antibodies have been described that detect sulfotyrosine. In dopaminergic cells in the brain, tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase.
TH is the rate-limiting enzyme involved in the synthesis of the neurotransmitter dopamine. Dopamine can be converted into other catecholamines, such as norepinephrine and epinephrine; the thyroid hormones triiodothyronine and thyroxine in the colloid of the thyroid are derived from tyrosine. The latex of Papaver somniferum, the opium poppy, has been shown to convert tyrosine into the alkaloid morphine and the bio-synthetic pathway has been established from tyrosine to morphine by using Carbon-14 radio-labelled tyrosine to trace the in-vivo synthetic route. Tyrosine ammonia lyase is an enzyme in the natural phenols biosynthesis pathway, it transforms L-tyrosine into p-coumaric acid. Tyrosine is the precursor to the pigment melanin. Tyrosine is needed to synthesize the benzoquinone structure which forms part of coenzyme Q10; the decomposition of L-tyrosine begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate. The positional description para, abbreviated p, mean that the hydroxyl group and side chain on the phenyl ring are across from each other.
The next oxidation step catalyzes by p-hydroxyphenylpyruvate dioxygenase and splitting off CO2 homogentisate. In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentisate 1,2-dioxygenase is required. Thereby, through the incorporation of a further O2 molecule, maleylacetoacetate is created. Fumarylacetoacetate is created by maleylacetoacetate cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation; this cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is split by the enzyme fumarylacetoacetate hydrolase through the addition of a water molecule. Thereby fumarate and acetoacetate are liberated. Acetoacetate is a ketone body, activated with succinyl-CoA, thereafter it can be converted into acetyl-CoA, which in turn can be oxidized by the citric acid cycle or be used for fatty acid synthesis. Phloretic acid is a urinary metabolite of tyrosine in rats. Three structural isomers of L-tyrosine are known.
In addition to the common a