Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the gram-staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found everywhere, in all environments on Earth that support life; the gram-negative bacteria include the model organism Escherichia coli, as well as many pathogenic bacteria, such as Pseudomonas aeruginosa, Neisseria gonorrhoeae, Chlamydia trachomatis, Yersinia pestis. They are an important medical challenge, as their outer membrane protects them from many antibiotics. Additionally, the outer leaflet of this membrane comprises a complex lipopolysaccharide whose lipid A component can cause a toxic reaction when these bacteria are lysed by immune cells; this toxic reaction can include fever, an increased respiratory rate, low blood pressure — a life-threatening condition known as septic shock.
Several classes of antibiotics have been designed to target gram-negative bacteria, including aminopenicillins, ureidopenicillins, beta-lactam-betalactamase combinations, Folate antagonists and carbapenems. Many of these antibiotics cover gram positive organisms; the drugs that target gram negative organisms include aminoglycosides and Ciprofloxacin. Gram-negative bacteria display these characteristics: An inner cell membrane is present A thin peptidoglycan layer is present Has outer membrane containing lipopolysaccharides in its outer leaflet and phospholipids in the inner leaflet Porins exist in the outer membrane, which act like pores for particular molecules Between the outer membrane and the cytoplasmic membrane there is a space filled with a concentrated gel-like substance called periplasm The S-layer is directly attached to the outer membrane rather than to the peptidoglycan If present, flagella have four supporting rings instead of two Teichoic acids or lipoteichoic acids are absent Lipoproteins are attached to the polysaccharide backbone Some contain Braun's lipoprotein, which serves as a link between the outer membrane and the peptidoglycan chain by a covalent bond Most, with few exceptions, do not form spores Along with cell shape, gram-staining is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria.
The kingdom Monera was divided into four divisions based on gram-staining: Firmacutes, Gracillicutes and Mendocutes. Since 1987, the monophyly of the gram-negative bacteria has been disproven with molecular studies; however some authors, such as Cavalier-Smith still treat them as a monophyletic taxon and refer to the group as a subkingdom "Negibacteria". Bacteria are traditionally classified based on their gram-staining response into the gram-positive and gram-negative groups, it was traditionally thought that the groups represent lineages, i.e. the extra membrane only evoved once, such that gram-negative bacteria are more related to one another than to any gram-positive bacteria. While this is true, the classification system breaks down in some cases, with lineage groupings not matching the staining result. Thus, gram-staining cannot be reliably used to assess familial relationships of bacteria. Staining gives reliable information about the composition of the cell membrane, distinguishing between the presence or absence of an outer lipid membrane.
Of these two structurally distinct groups of prokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon a number of different observations including that the gram-positive bacteria are the major reactors to antibiotics and that gram-negative bacteria are, in general, resistant to them, it has been proposed that the outer cell membrane in gram-negative bacteria evolved as a protective mechanism against antibiotic selection pressure; some bacteria such as Deinococcus, which stain gram-positive due to the presence of a thick peptidoglycan layer, but possess an outer cell membrane are suggested as intermediates in the transition between monoderm and diderm bacteria. The diderm bacteria can be further differentiated between simple diderms lacking lipopolysaccharide; the conventional LPS-diderm group of gram-negative bacteria are uniquely identified by a few conserved signature indel in the HSP60 protein. In addition, a number of bacterial taxa that are either part of the phylum Firmicutes or branches in its proximity are found to possess a diderm cell structure.
They lack the GroEL signature. The presence of this CSI in all se
DD-transpeptidase is a bacterial enzyme that catalyzes the transfer of the R-L-aca-D-alanyl moiety of R-L-aca-D-alanyl-D-alanine carbonyl donors to the γ-OH of their active-site serine and from this to a final acceptor. It is involved in bacterial cell wall biosynthesis, the transpeptidation that crosslinks the peptide side chains of peptidoglycan strands; the antibiotic penicillin irreversibly binds to and inhibits the activity of the transpeptidase enzyme by forming a stable penicilloyl-enzyme intermediate. Because of the interaction between penicillin and transpeptidase, this enzyme is known as penicillin-binding protein. DD-transpeptidase is mechanistically similar to the proteolytic reactions of the trypsin protein family. Crosslinking of peptidyl moieties of adjacent glycan strands is a two-step reaction; the first step involves the cleavage of the D-alanyl-D-alanine bond of a peptide unit precursor acting as carbonyl donor, the release of the carboxyl-terminal D-alanine, the formation of the acyl-enzyme.
The second step involves the breakdown of the acyl-enzyme intermediate and the formation of a new peptide bond between the carbonyl of the D-alanyl moiety and theamino group of another peptide unit. Most discussion of DD-peptidase mechanisms revolves around the catalysts of proton transfer. During formation of the acyl-enzyme intermediate, a proton must be removed from the active site serine hydroxyl group and one must be added to the amine leaving group. A similar proton movement must be facilitated in deacylation; the identity of the general acid and base catalysts involved in these proton transfers has not yet been elucidated. However, the catalytic triad tyrosine and serine, as well as serine, serine have been proposed. Transpeptidases are members of the penicilloyl-serine transferase superfamily, which has a signature SxxK conserved motif. With "x" denoting a variable amino acid residue, the transpeptidases of this superfamily show a trend in the form of three motifs: SxxK, SxN, KTG; these motifs occur at equivalent places, are equally spaced, along the polypeptide chain.
The folded protein brings these motifs close to each other at the catalytic center between an all-α domain and an α/β domain. With "x" denoting a variable amino acid residue, the transpeptidases of this superfamily show a trend in the form of three motifs: SxxK, SxN, KTG; these motifs occur at equivalent places, are equally spaced, along the polypeptide chain. The folded protein brings these motifs close to each other at the catalytic center between an all-α domain and an α/β domain; the structure of the streptomyces K15 DD-transpeptidase has been studied, consists of a single polypeptide chain organized into two domains. One domain contains α-helices, the second one is of α/β-type; the center of the catalytic cleft is occupied by the Ser35-Thr36-Thr37-Lys38 tetrad, which includes the nucleophilic Ser35 residue at the amino-terminal end of helix α2. One side of the cavity is defined by the Ser96-Gly97-Cys98 loop connecting helices α4 and α5; the Lys213-Thr214-Gly215 triad lies on strand β3 on the opposite side of the cavity.
The backbone NH group of the essential Ser35 residue and that of Ser216 downstream from the motif Lys213-Thr214-Gly215 occupy positions that are compatible with the oxyanion hole function required for catalysis. The enzyme is classified as a DD-transpeptidase because the susceptible peptide bond of the carbonyl donor extends between two carbon atoms with the D-configuration. All bacteria possess at least one, most several, monofunctional serine DD-peptidases; this enzyme is an excellent drug target because it is essential, is accessible from the periplasm, has no equivalent in mammalian cells. DD-transpeptidase is the target protein of β-lactam antibiotics This is because the structure of the β-lactam resembles the D-ala-D-ala residue. Β-lactams exert their effect by competitively inactivating the serine DD-transpeptidase catalytic site. Penicillin is a cyclic analogue of the D-Ala-D-Ala terminated carbonyl donors, therefore in the presence of this antibiotic, the reaction stops at the level of the serine ester-linked penicilloyl enzyme.
Thus β-lactam antibiotics force these enzymes to behave like penicillin binding proteins. Kinetically, the interaction between the DD-peptidase and beta-lactams is a three-step reaction: E + I ⇌ E ⋅ I → E − I ∗ → E + P Beta-Iactams may form an adduct E-I* of high stability with DD-transpeptidase; the half life of this adduct is around hours, whereas the half-life of the normal reaction is in the order of milliseconds. The interference with the enzyme processes responsible for cell wall formation results in cellular lysis and death due to the triggering of the autolytic system in the bacteria. Vancomycin, an antibiotic that binds the D-ala-D-ala residues, inhibiting elongation via glycosyltransferase The MEROPS online database for peptidases and their inhibitors: S11.001 EC 126.96.36.199 Serine-Type+D-Ala-D-Ala+Carboxypeptidase at the US National Library of Medicine Medical Subject Headings
The cytosol known as intracellular fluid or cytoplasmic matrix, is the liquid found inside cells. It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which comprises the mitochondria and other organelles; the cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles; the cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and properties within cells is not well understood; the concentrations of ions such as sodium and potassium are different in the cytosol than in the extracellular fluid.
The cytosol contains large amounts of macromolecules, which can alter how molecules behave, through macromolecular crowding. Although it was once thought to be a simple solution of molecules, the cytosol has multiple levels of organization; these include concentration gradients of small molecules such as calcium, large complexes of enzymes that act together and take part in metabolic pathways, protein complexes such as proteasomes and carboxysomes that enclose and separate parts of the cytosol. The term "cytosol" was first introduced in 1965 by H. A. Lardy, referred to the liquid, produced by breaking cells apart and pelleting all the insoluble components by ultracentrifugation; such a soluble cell extract is not identical to the soluble part of the cell cytoplasm and is called a cytoplasmic fraction. The term cytosol is now used to refer to the liquid phase of the cytoplasm in an intact cell; this excludes any part of the cytoplasm, contained within organelles. Due to the possibility of confusion between the use of the word "cytosol" to refer to both extracts of cells and the soluble part of the cytoplasm in intact cells, the phrase "aqueous cytoplasm" has been used to describe the liquid contents of the cytoplasm of living cells.
Prior to this, other terms, including "hyaloplasm", were used for the cell fluid, not always synonymously, as its nature was not clear. The proportion of cell volume, cytosol varies: for example while this compartment forms the bulk of cell structure in bacteria, in plant cells the main compartment is the large central vacuole; the cytosol consists of water, dissolved ions, small molecules, large water-soluble molecules. The majority of these non-protein molecules have a molecular mass of less than 300 Da; this mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism is immense. For example, up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell. Estimates of the number of metabolites in single cells such as E. coli and baker's yeast predict that under 1,000 are made. Most of the cytosol is water; the pH of the intracellular fluid is 7.4. While human cytosolic pH ranges between 7.0 - 7.4, is higher if a cell is growing.
The viscosity of cytoplasm is the same as pure water, although diffusion of small molecules through this liquid is about fourfold slower than in pure water, due to collisions with the large numbers of macromolecules in the cytosol. Studies in the brine shrimp have examined. Although water is vital for life, the structure of this water in the cytosol is not well understood because methods such as nuclear magnetic resonance spectroscopy only give information on the average structure of water, cannot measure local variations at the microscopic scale; the structure of pure water is poorly understood, due to the ability of water to form structures such as water clusters through hydrogen bonds. The classic view of water in cells is that about 5% of this water is bound in by solutes or macromolecules as water of solvation, while the majority has the same structure as pure water; this water of solvation is not active in osmosis and may have different solvent properties, so that some dissolved molecules are excluded, while others become concentrated.
However, others argue that the effects of the high concentrations of macromolecules in cells extend throughout the cytosol and that water in cells behaves differently from the water in dilute solutions. These ideas include the proposal that cells contain zones of low and high-density water, which could have widespread effects on the structures and functions of the other parts of the cell. However, the use of advanced nuclear magnetic resonance methods to directly measure the mobility of water in living cells contradicts this idea, as it suggests that 85% of cell water acts like that pure water, while the remainder is less mobile and bound to macromolecules; the concentrations of the other ions in cytosol are quite different from those in extracellular flui
Proteoglycans are proteins that are glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain; the point of attachment is a serine residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge. The Ser residue is in the sequence -Ser-Gly-X-Gly-, although not every protein with this sequence has an attached glycosaminoglycan; the chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions due to the occurrence of sulfate and uronic acid groups. Proteoglycans occur in the connective tissue. Proteoglycans are categorized by their relative size and the nature of their glycosaminoglycan chains. Types include: Certain members are considered members of the "small leucine-rich proteoglycan family"; these include decorin, biglycan and lumican. Proteoglycans are a major component of the animal extracellular matrix, the "filler" substance existing between cells in an organism.
Here they form large complexes, both to other proteoglycans, to hyaluronan, to fibrous matrix proteins, such as collagen. The combination of proteoglycans and collagen form cartilage, a sturdy tissue, heavily hydrated, they are involved in binding cations and water, regulating the movement of molecules through the matrix. Evidence shows they can affect the activity and stability of proteins and signalling molecules within the matrix. Individual functions of proteoglycans can be attributed to either the protein core or the attached GAG chain, they can serve as lubricants. The protein component of proteoglycans is synthesized by ribosomes and translocated into the lumen of the rough endoplasmic reticulum. Glycosylation of the proteoglycan occurs in the Golgi apparatus in multiple enzymatic steps. First a special link tetrasaccharide is attached to a serine side chain on the core protein to serve as a primer for polysaccharide growth. Sugars are added one at a time by glycosyl transferase; the completed proteoglycan is exported in secretory vesicles to the extracellular matrix of the tissue.
An inability to break down proteoglycans is characteristic of a group of genetic disorders, called mucopolysaccharidoses. The inactivity of specific lysosomal enzymes that degrade glycosaminoglycans leads to the accumulation of proteoglycans within cells; this leads to a variety of disease symptoms, depending upon the type of proteoglycan, not degraded. Diagram at nd.edu
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough and sometimes rigid, it provides the cell with both structural support and protection, acts as a filtering mechanism. Cell walls are present in most prokaryotes, in algae and fungi but in other eukaryotes including animals. A major function is to act as pressure vessels, preventing over-expansion of the cell when water enters; the composition of cell walls varies between species and may depend on cell type and developmental stage. The primary cell wall of land plants is composed of the polysaccharides cellulose and pectin. Other polymers such as lignin, suberin or cutin are anchored to or embedded in plant cell walls. Algae possess cell walls made of glycoproteins and polysaccharides such as carrageenan and agar that are absent from land plants. In bacteria, the cell wall is composed of peptidoglycan; the cell walls of archaea have various compositions, may be formed of glycoprotein S-layers, pseudopeptidoglycan, or polysaccharides.
Fungi possess cell walls made of the N-acetylglucosamine polymer chitin. Unusually, diatoms have a cell wall composed of biogenic silica. A plant cell wall was first observed and named by Robert Hooke in 1665. However, "the dead excrusion product of the living protoplast" was forgotten, for three centuries, being the subject of scientific interest as a resource for industrial processing or in relation to animal or human health. In 1804, Karl Rudolphi and J. H. F. Link proved. Before, it had been thought that fluid passed between them this way; the mode of formation of the cell wall was controversial in the 19th century. Hugo von Mohl advocated the idea. Carl Nägeli believed that the growth of the wall in thickness and in area was due to a process termed intussusception; each theory was improved in the following decades: the apposition theory by Eduard Strasburger, the intussusception theory by Julius Wiesner. In 1930, Ernst Münch coined the term apoplast in order to separate the "living" symplast from the "dead" plant region, the latter of which included the cell wall.
By the 1980s, some authors suggested replacing the term "cell wall" as it was used for plants, with the more precise term "extracellular matrix", as used for animal cells, but others preferred the older term. Cell walls serve similar purposes in those organisms, they may give cells offering protection against mechanical stress. In multicellular organisms, they permit the organism to hold a definite shape. Cell walls limit the entry of large molecules that may be toxic to the cell, they further permit the creation of stable osmotic environments by preventing osmotic lysis and helping to retain water. Their composition and form may change during the cell cycle and depend on growth conditions. In most cells, the cell wall is flexible, meaning that it will bend rather than holding a fixed shape, but has considerable tensile strength; the apparent rigidity of primary plant tissues is enabled by cell walls, but is not due to the walls' stiffness. Hydraulic turgor pressure creates this rigidity, along with the wall structure.
The flexibility of the cell walls is seen when plants wilt, so that the stems and leaves begin to droop, or in seaweeds that bend in water currents. As John Howland explains Think of the cell wall as a wicker basket in which a balloon has been inflated so that it exerts pressure from the inside; such a basket is rigid and resistant to mechanical damage. Thus does the prokaryote cell gain strength from a flexible plasma membrane pressing against a rigid cell wall; the apparent rigidity of the cell wall thus results from inflation of the cell contained within. This inflation is a result of the passive uptake of water. In plants, a secondary cell wall is a thicker additional layer of cellulose which increases wall rigidity. Additional layers may be formed by suberin in cork cell walls; these compounds are rigid and waterproof. Both wood and bark cells of trees have secondary walls. Other parts of plants such as the leaf stalk may acquire similar reinforcement to resist the strain of physical forces.
The primary cell wall of most plant cells is permeable to small molecules including small proteins, with size exclusion estimated to be 30-60 kDa. The pH is an important factor governing the transport of molecules through cell walls. Cell walls evolved independently including within the photosynthetic eukaryotes. In these lineages, the cell wall is related to the evolution of multicellularity, terrestrialization and vascularization; the walls of plant cells must have sufficient tensile strength to withstand internal osmotic pressures of several times atmospheric pressure that result from the difference in solute concentration between the cell interior and external solutions. Plant cell walls vary from 0.1 to several µm in thickness. Up to three strata or layers may be found in plant cell walls: The primary cell wall a thin and extensible layer formed while the cell is growing; the secondary cell wall, a thick layer formed inside the primary cell wall after the cell is grown. It is not found in all cell types.
Some cells, such as the conducting cells in xylem, possess a secondary wall containing lignin, which strengthens and waterproofs the wall. The middle lamella, a layer rich in pectins; this outermost layer
In chemistry and biology a cross-link is a bond that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural polymers. In polymer chemistry "cross-linking" refers to the use of cross-links to promote a change in the polymers' physical properties; when "crosslinking" is used in the biological field, it refers to the use of a probe to link proteins together to check for protein–protein interactions, as well as other creative cross-linking methodologies. Although the term is used to refer to the "linking of polymer chains" for both sciences, the extent of crosslinking and specificities of the crosslinking agents vary greatly; as with all science, there are overlaps, the following delineations are a starting point to understanding the subtleties. Crosslinking is the general term for the process of forming covalent bonds or short sequences of chemical bonds to join two polymer chains together; the term curing refers to the crosslinking of thermosetting resins, such as unsaturated polyester and epoxy resin, the term vulcanization is characteristically used for rubbers.
When polymer chains are crosslinked, the material becomes more rigid. In polymer chemistry, when a synthetic polymer is said to be "cross-linked", it means that the entire bulk of the polymer has been exposed to the cross-linking method; the resulting modification of mechanical properties depends on the cross-link density. Low cross-link densities decrease the viscosities of polymer melts. Intermediate cross-link densities transform gummy polymers into materials that have elastomeric properties and high strengths. High cross-link densities can cause materials to become rigid or glassy, such as phenol-formaldehyde materials. Cross-links can be formed by chemical reactions that are initiated by heat, change in pH, or irradiation. For example, mixing of an unpolymerized or polymerized resin with specific chemicals called crosslinking reagents results in a chemical reaction that forms cross-links. Cross-linking can be induced in materials that are thermoplastic through exposure to a radiation source, such as electron beam exposure, gamma radiation, or UV light.
For example, electron beam processing is used to cross-link the C type of cross-linked polyethylene. Other types of cross-linked polyethylene are made by addition of peroxide during extruding or by addition of a cross-linking agent and a catalyst during extruding and performing a post-extrusion curing; the chemical process of vulcanization is a type of cross-linking that changes rubber to the hard, durable material associated with car and bike tires. This process is called sulfur curing; this is, however, a slower process. A typical car tire is cured for 15 minutes at 150 °C. However, the time can be reduced by the addition of accelerators such as 2-benzothiazolethiol or tetramethylthiuram disulfide. Both of these contain a sulfur atom in the molecule that initiates the reaction of the sulfur chains with the rubber. Accelerators increase the rate of cure by catalysing the addition of sulfur chains to the rubber molecules. Cross-links are the characteristic property of thermosetting plastic materials.
In most cases, cross-linking is irreversible, the resulting thermosetting material will degrade or burn if heated, without melting. In the case of commercially used plastics, once a substance is cross-linked, the product is hard or impossible to recycle. In some cases, though, if the cross-link bonds are sufficiently different, from the bonds forming the polymers, the process can be reversed. Permanent wave solutions, for example, break and re-form occurring cross-links between protein chains in hair. Where chemical cross-links are covalent bonds, physical cross-links are formed by weak interactions. For example, sodium alginate gels upon exposure to calcium ion, which allows it to form ionic bonds that bridge between alginate chains. Polyvinyl alcohol gels upon the addition of borax through hydrogen bonding between boric acid and the polymer's alcohol groups. Other examples of materials which form physically cross-linked gels include gelatin, collagen and agar agar. Chemical covalent cross-links are stable mechanically and thermally, so once formed are difficult to break.
Therefore, cross-linked products like car tires cannot be recycled easily. A class of polymers known as thermoplastic elastomers rely on physical cross-links in their microstructure to achieve stability, are used in non-tire applications, such as snowmobile tracks, catheters for medical use, they offer a much wider range of properties than conventional cross-linked elastomers because the domains that act as cross-links are reversible, so can be reformed by heat. The stabilizing domains may be crystalline as in thermoplastic copolyesters. Note: A rubber which cannot be reformed by heat or chemical treatment is called a thermoset elastomer. On the other hand, a thermoplastic elastomer can be recycled by heat. Many polymers undergo oxidative cross-linking when exposed to atmospheric oxygen. In some cases this is undesirable and thus polymerization reactions may involve the use of an antioxidant to slow the formation of oxidative cross-links. In other cases, when formation of cross-links by oxidation is desirable, an oxidizer such as hydrogen peroxide may be used to speed up the process.
The aforementioned process of applying a permanent wave to hair is one example of oxidative cross-linking. In that process the disulfide bonds
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