Collagen is the main protein Proteins are organic compounds made of amino acids arranged in a linear chain. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In of connective tissue Connective tissue is a form of fibrous tissue.. It is one of the four types of tissue in traditional classifications in animals Animals are a major group of mostly multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and independently. Most animals are also and the most abundant protein in mammals Mammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain,^[1] making up about 25% to 35% of the whole-body protein content. It is naturally found exclusively in metazoa Animals are a major group of mostly multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and independently. Most animals are also, including sponges A Sponge are animals of the phylum Porifera . Their bodies consist of jelly-like mesohyl sandwiched between two thin layers of cells. While all animals have unspecialized cells that can transform into specialized cells, sponges are unique in having some specialized cells that can transform into other types, often migrating between the main cell. ^[2] In muscle tissue it serves as a major component of endomysium The endomysium, literally meaning within the muscle, is a layer of connective tissue that ensheaths a muscle fiber and is composed mostly from reticular fibers. It also contains capillaries, nerves and lymphatics. Collagen constitutes 1% to 2% of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles.^[3] The gelatin Gelatin is a translucent, colourless, brittle, nearly tasteless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning in a similar way are called gelatinous. Gelatin is an used in food and industry is derived from the partial hydrolysis Hydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization. Such polymer degradation is usually catalysed by of collagen.

Uses

Collagen is one of the long, fibrous structural proteins Scleroproteins are one of the two main classes of protein tertiary structure whose functions are quite different from those of globular proteins Globular proteins, or spheroproteins are one of the two main protein classes, comprising "globe"-like proteins that are more or less soluble in aqueous solutions . This main characteristic helps distinguishing them from fibrous proteins (the other class), which are practically insoluble such as enzymes Enzymes are biomolecules that catalyze chemical reactions. Nearly all known enzymes are proteins. However, certain RNA molecules can be effective biocatalysts too. These RNA molecules have come to be known as ribozymes. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into. Tough bundles of collagen called collagen fibers are a major component of the extracellular matrix In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has great tensile strength Tensile strength is indicated by the maxima of a stress-strain curve and, in general, indicates when necking will occur. As it is an intensive property, its value does not depend on the size of the test specimen. It is, however, dependent on the preparation of the specimen and the temperature of the test environment and material, and is the main component of fascia Fascia , pl. fas·ci·ae (făsh'ē-ē), adj. fascial (făsh'ē-əl) (from latin: a band) is the soft tissue component of the connective tissue system that permeates the human body. It interpenetrates and surrounds muscles, bones, organs, nerves, blood vessels and other structures. Fascia is an uninterrupted, three-dimensional web of tissue that, cartilage Cartilage is a type of dense connective tissue. It is composed of specialized cells called chondrocytes that produce a large amount of extracellular matrix composed of collagen fibers, abundant ground substance rich in proteoglycan, and elastin fibers. Cartilage is classified in three types, elastic cartilage, hyaline cartilage and fibrocartilage,, ligaments The study of ligaments is known as desmology, tendons A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fascia as they are both made of collagen except that ligaments join one bone to another bone, and fascia connect muscles to other muscles. Tendons and muscles work together and can, bone Bones are rigid organs that form part of the endoskeleton of vertebrates. They function to move, support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue. Because bones come in a variety of shapes and have a complex internal and external structure and skin. Along with soft keratin Keratins are a family of fibrous structural proteins; tough and insoluble, they form the hard but mineralized structures found in reptiles, birds, amphibians, and mammals. They are rivaled as biological materials in toughness only by chitin, it is responsible for skin The skin is the outer covering of the body. In humans, it is the largest organ of the integumentary system made up of multiple layers of epithelial tissues, and guards the underlying muscles, bones, ligaments and internal organs. Skin of a different nature exists in amphibians, reptiles, birds. Human skin is not unlike that of most other mammals strength and elasticity, and its degradation leads to wrinkles A wrinkle is a fold, ridge or crease in the skin. Skin wrinkles typically appear as a result of aging processes such as glycation or, temporarily, as the result of prolonged immersion in water. Wrinkling in the skin is caused by habitual facial expressions, aging, sun damage, smoking, poor hydration, and various other factors. With prolonged water that accompany aging Ageing or aging (American and Canadian English) is the accumulation of changes in an organism or object over time. Aging in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of aging grow and expand over time, while others decline. Reaction time, for example, may slow with age, while. It strengthens blood vessels The blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart, the capillaries, which enable the actual exchange of water and chemicals between the blood and the tissues; and the veins, which carry blood from and plays a role in tissue Tissue is a cellular organizational level intermediate between cells and a complete organism. Hence, a tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. Organs are then formed by the functional grouping together of multiple tissues development. It is present in the cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is approximately 43 dioptres. While the cornea contributes most of the eye' and lens of the eye Eyes are organs that detect light, and send signals along the optic nerve to the visual and other areas of the brain[citation needed]. Complex optical systems with resolving power have come in ten fundamentally different forms, and 96% of animal species possess a complex optical system. Image-resolving eyes are present in cnidaria, molluscs, in crystalline A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is crystallography. The process of crystal formation via mechanisms of crystal growth is called crystallization form. It is also used in cosmetic surgery Plastic surgery is a medical specialty concerned with the correction or restoration of form and function. While famous for aesthetic surgery, plastic surgery also includes two main fields: cosmetic and reconstructive surgery. The word "plastic" derives from the Greek plastikos meaning to mold or to shape; its use here is not connected and burns surgery A burn is a type of injury that may be caused by heat, cold, electricity, chemicals, light, radiation, or friction. Burns can be highly variable in terms of the tissue affected, the severity, and resultant complications. Muscle, bone, blood vessel, and epidermal tissue can all be damaged with subsequent pain due to profound injury to nerves. Hydrolyzed collagen can play an important role in weight management, as a protein, it can be advantageously used for its satiating power.^{[citation needed]}

Industrial uses

If collagen is sufficiently hydrolyzed Hydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization. Such polymer degradation is usually catalysed by, the three tropocollagen strands separate partially or completely into globular domains, containing a different secondary structure to the normal collagen polyproline II (PPII), e.g. random coils A random coil is a polymer conformation where the monomer subunits are oriented randomly while still being bonded to adjacent units. It is not one specific shape, but a statistical distribution of shapes for all the chains in a population of macromolecules. The conformation's name is derived from the idea that, in the absence of specific,. This process describes the formation of gelatin Gelatin is a translucent, colourless, brittle, nearly tasteless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning in a similar way are called gelatinous. Gelatin is an, which is used in many foods Food is any substance, usually composed of carbohydrates, fats, proteins and water, that can be eaten or drunk by an animal or human for nutrition or pleasure. Items considered food may be sourced from plants, animals or other categories such as fungus or fermented products like alcohol. Although many human cultures sought food items through, including flavored gelatin desserts The most common culinary use for gelatin is as a main ingredient in varieties of gelatin desserts. Unprepared gelatin for desserts is often marketed as a flavored powder or concentrated gelatinous solid. Prepared gelatin desserts are marketed in a variety of forms. Popular brands include Jell-O and Knox from Kraft Foods in North America, Royal in. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries.^[4] From a nutritional point of view, collagen and gelatin are a poor-quality sole source of protein since they do not contain all the essential amino acids An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet in the proportions that the human body requires—they are not 'complete proteins A complete protein is a source of protein that contains an adequate proportion of all of the essential amino acids for the dietary needs of humans or other animals' (as defined by food science, not that they are partially structured). Manufacturers of collagen-based dietary supplements A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to provide nutrients, such as vitamins, minerals, fatty acids or amino acids, that are missing or are not consumed in sufficient quantity in a person's diet. Some countries define dietary supplements as foods, while in others they are defined claim that their products can improve skin and fingernail quality as well as joint health. However, mainstream scientific research has not shown strong evidence to support these claims. Individuals with problems in these areas are more likely to be suffering from some other underlying condition (such as normal aging, dry skin, arthritis etc.) rather than just a protein deficiency.

From the Greek for glue, kolla, the word collagen means "glue An animal glue is an adhesive that is created by prolonged boiling of animal connective tissue producer" and refers to the early process of boiling the skin and sinews A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fascia as they are both made of collagen except that ligaments join one bone to another bone, and fascia connect muscles to other muscles. Tendons and muscles work together and can of horses The horse is a hoofed (ungulate) mammal, a subspecies of one of seven extant species of the family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today. Humans began to domesticate horses around 4000 BC, and their domestication is believed to have been and other animals to obtain glue. Collagen adhesive was used by Egyptians Egypt (pronounced /ˈiːdʒɪpt/ ; Arabic: مصر‎ Miṣr, pronounced [misˤɾ] ( listen); Egyptian Arabic: Maṣr [ˈmɑsˤɾ]; Coptic: Ⲭⲏⲙⲓ, kīmi; Egyptian: Kemet), officially the Arab Republic of Egypt, is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Western Asia. Covering an area of about 1,010, about 4,000 years ago, and Native Americans Native Americans in the United States are the indigenous peoples from the regions of North America now encompassed by the continental United States, including parts of Alaska and the island state of Hawaii. They comprise a large number of distinct tribes, states, and ethnic groups, many of which survive as intact political communities. There has used it in bows A bow is a weapon that projects arrows powered by the elasticity of the bow. Essentially, it is a form of spring. As the bow is drawn, energy is stored in the limbs of the bow and transformed into rapid motion when the string is released, with the string transferring this force to the arrow. Bows are used for hunting, sport , or as weapons of war about 1,500 years ago. The oldest glue in the world, carbon-dated Radiocarbon dating, or carbon dating, is a radiometric dating method that uses the naturally occurring radioisotope carbon-14 to determine the age of carbonaceous materials up to about 60,000 years. Raw, i.e. uncalibrated, radiocarbon ages are usually reported in radiocarbon years "Before Present" (BP), "Present" being defined as more than 8,000 years old, was found to be collagen—used as a protective lining on rope baskets and embroidered Embroidery is the art or handicraft of decorating fabric or other materials with needle and thread or yarn. Embroidery may also incorporate other materials such as metal strips, pearls, beads, quills, and sequins fabrics A textile is a flexible material consisting of a network of natural or artificial fibres often referred to as thread or yarn. Yarn is produced by spinning raw wool fibres, linen, cotton, or other material on a spinning wheel to produce long strands known as yarn. Textiles are formed by weaving, knitting, crocheting, knotting, or pressing fibres, and to hold utensils together; also in crisscross decorations on human A human is a member of a species of bipedal primates in the family Hominidae . DNA and fossil evidence indicates that modern humans originated in east Africa about 200,000 years ago. When compared to other animals and primates, humans have a highly developed brain, capable of abstract reasoning, language, introspection and problem solving. This skulls The skull is a bony structure found in the head of many animals. The skull supports the structures of the face and protects the head against injury.^[5] Collagen normally converts to gelatin, but survived due to the dry conditions. Animal glues are thermoplastic A thermoplastic is a polymer that turns to a liquid when heated and freezes to a very glassy state when cooled sufficiently. Most thermoplastics are high-molecular-weight polymers whose chains associate through weak Van der Waals forces ; stronger dipole-dipole interactions and hydrogen bonding (nylon); or even stacking of aromatic rings (, softening again upon reheating, and so they are still used in making musical instruments such as fine violins and guitars, which may have to be reopened for repairs—an application incompatible with tough, synthetic plastic adhesives, which are permanent. Animal sinews and skins, including leather, have been used to make useful articles for millennia.

Gelatin-resorcinol-formaldehyde glue (and with formaldehyde replaced by less-toxic pentanedial and ethanedial) has been used to repair experimental incisions in rabbit lungs.^[6]

Medical uses

Collagen has been widely used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic and surgical purposes. Some points of interest are:

1. when used cosmetically, there is a chance of allergic reactions causing prolonged redness; however, this can be virtually eliminated by simple and inconspicuous patch testing prior to cosmetic use, and
2. most medical collagen is derived from young beef cattle (bovine) from certified BSE (Bovine spongiform encephalopathy) free animals. Most manufacturers use donor animals from either "closed herds", or from countries which have never had a reported case of BSE such as Australia, Brazil and New Zealand.
3. porcine (pig) tissue is also widely used for producing collagen sheet for a variety of surgical purposes.
4. alternatives using the patient's own fat, hyaluronic acid or polyacrylamide gel are readily available.

Collagens are widely employed in the construction of artificial skin substitutes used in the management of severe burns. These collagens may be derived from bovine, equine or porcine, and even human, sources and are sometimes used in combination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances.

Collagen is also sold commercially as a joint mobility supplement^[7]. Because proteins are broken down into amino acids before absorption, there is no reason for orally ingested collagen to affect connective tissue in the body, except through the effect of individual amino acid supplementation.

Recently an alternative to animal-derived collagen has become available. Although expensive, this human collagen, derived from donor cadavers, placentas and aborted fetuses, may minimize the possibility of immune reactions.

Although it cannot be absorbed through the skin, collagen is now being used as a main ingredient for some cosmetic makeup.^[8]

Conformation and structure

Collagen structure is complex. Its conformation can be considered at the monomeric level (individual collagen molecules) and/or at its aggregate level (how the trimers are arranged), i.e. their packing structure (fibrils, networks, etc.—see below)^[9].

History and background

The molecular and packing structures of collagen have eluded scientists for decades; the first evidence that it possess a regular structure at the molecular level was presented in the mid-1930s ^{[10] [11]}. Since that time many prominent scholars, including (but not limited to) Nobel laureate Crick, and Pauling, Rich, Yonath, Brodsky, Berman and Ramachandran concentrated on the conformation of the collagen monomer. Several competing models although correctly dealing with the conformation of each individual peptide chain, gave way to the triple-helical "Madras" model which provided an essentially correct model of the molecule's quaternary structure ^[12][13][14] although this model still required some refinement ^{[15][16][17][18]}. The packing structure of collagen has not been defined to the same degree outside of the fibrillar collagen types, although it has been long known to be hexagonal or quasi-hexagonal ^[19][20][21]. As with its monomeric structure, several conflicting models alleged that either the packing arrangement of collagen molecules is ‘sheet-like’ or microfibrillar.^[22][23] Recently it was confirmed that the microfibrillar structure as described by Fraser, Miller, Wess (amongst others) was closest to the observed structure, although it over-simplified the topological progression of neighboring collagen molecules and hence did not predict the correct conformation of the discontinuous D-periodic pentameric arrangement termed simply: the microfibril^[24]

Molecular structure

The tropocollagen or "collagen molecule" is a subunit of larger collagen aggregates such as fibrils. It is approximately 300 nm long and 1.5 nm in diameter, made up of three polypeptide strands (called alpha peptides), each possessing the conformation of a left-handed helix (its name is not to be confused with the commonly occurring alpha helix, a right-handed structure). These three left-handed helices are twisted together into a right-handed coiled coil, a triple helix or "super helix", a cooperative quaternary structure stabilized by numerous hydrogen bonds. With type I collagen and possibly all fibrillar collagens if not all collagens, each triple-helix associates into a right-handed super-super-coil that is referred to as the collagen microfibril. Each microfibril is interdigitated with its neighboring microfibrils to a degree that might suggest that they are individually unstable although within collagen fibrils they are so well ordered as to be crystalline.

A distinctive feature of collagen is the regular arrangement of amino acids in each of the three chains of these collagen subunits. The sequence often follows the pattern Gly-Pro-Y or Gly-X-Hyp, where X and Y may be any of various other amino acid residues. Proline or hydroxyproline constitute about 1/6 of the total sequence. With Glycine accounting for the 1/3 of the sequence, this means that approximately half of the collagen sequence is not glycine, proline or hydroxyproline, a fact often missed due to the distraction of the unusual GXY character of collagen alpha-peptides. This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk fibroin. 75-80% of silk is (approximately) -Gly-Ala-Gly-Ala- with 10% serine—and elastin is rich in glycine, proline, and alanine (Ala), whose side group is a small, inert methyl group. Such high glycine and regular repetitions are never found in globular proteins save for very short sections of their sequence. Chemically-reactive side groups are not needed in structural proteins as they are in enzymes and transport proteins, however collagen is not quite just a structural protein. Due to its key role in the determination of cell phenotype, cell adhesion, tissue regulation and infrastructure, many sections of its non-proline rich regions have cell or matrix association / regulation roles. The relatively high content of Proline and Hydroxyproline rings, with their geometrically constrained carboxyl and (secondary) amino groups, along with the rich abundance of glycine, accounts for the tendency of the individual polypeptide strands to form left-handed helices spontaneously, without any intrachain hydrogen bonding.

Because glycine is the smallest amino acid with no side-chain, it plays a unique role in fibrous structural proteins. In collagen, Gly is required at every third position because the assembly of the triple helix puts this residue at the interior (axis) of the helix, where there is no space for a larger side group than glycine’s single hydrogen atom. For the same reason, the rings of the Pro and Hyp must point outward. These two amino acids help stabilize the triple helix—Hyp even more so than Pro—a lower concentration of them is required in animals such as fish, whose body temperatures are lower than most warm-blooded animals.

Fibrillar structure

The tropocollagen subunits spontaneously self-assemble, with regularly staggered ends, into even larger arrays in the extracellular spaces of tissues^[25][26]. In the fibrillar collagens, the molecules are staggered from each other by about 67nm (a unit that is referred to as ‘D’ and changes depending upon the hydration state of the aggregate). Each D-period contains 4 and a fraction collagen molecules. This is because 300 nm divided by 67 nm does not give an integer (the length of the collagen molecule divided by the stagger distance D). Therefore in each D-period repeat of the microfibril, there is a part containing five molecules in cross-section—called the “overlap” and a part containing only 4 molecules.^[24] The triple-helices are also arranged in a hexagonal or quasi-hexagonal array in cross-section, in both the gap and overlap regions.^[24][27].

There is some covalent crosslinking within the triple helices, and a variable amount of covalent crosslinking between tropocollagen helices forming well organized aggregates (such as fibrils)^[28]. Larger fibrillar bundles are formed with the aid of several different classes of proteins (including different collagen types), glycoproteins and proteoglycans to form the different types of mature tissues from alternate combinations of the same key players^[29]. Collagen's insolubility was a barrier to the study of monomeric collagen until it was found that tropocollagen from young animals can be extracted because it is not yet fully crosslinked. However, advances in microscopy techniques (Electron Microscopy (EM) and Atomic Force Microscopy (AFM)) and X-ray diffraction have enabled researchers to obtain increasingly detailed images of collagen structure in situ. These later advances are particularly important to better understanding the way in which collagen structure affects cell-cell and cell-matrix communication and how tissues are constructed in growth and repair, and changed in development and disease^[30][31].

Collagen fibrils are semi-crystalline aggregates of collagen molecules. Collagen fibers are bundles of fibrils.

Collagen fibrils/aggregates are arranged in different combinations and concentrations in various tissues to provide varying tissue properties. In bone, entire collagen triple helices lie in a parallel, staggered array. 40 nm gaps between the ends of the tropocollagen subunits (approximately equal to the gap region) probably serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component, which is (approximately) hydroxyapatite, Ca₁₀(PO₄)₆(OH)₂ with some phosphate. It is in this way that certain kinds of cartilage turn into bone. Type I collagen gives bone its tensile strength.

Types and associated disorders

Collagen occurs in many places throughout the body. The 29 types of collagen have thus far been identified and described in literature. Over 90% of the collagen in the body, however, are of type I, II, III, and IV.

• Collagen One: skin, tendon, vascular, ligature, organs, bone (main component of bone)
• Collagen Two: cartilage (main component of cartilage)
• Collagen Three: reticulate (main component of reticular fibers), commonly found alongside type I.
• Collagen Four: forms bases of cell basement membrane

Collagen diseases commonly arise from genetic defects that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes in the normal production of collagen.

In addition to the above mentioned disorders, excessive deposition of collagen occurs in Scleroderma.

Staining

In histology, collagen is brightly eosinophilic (pink) in standard H&E slides. The dye methyl violet may be used to stain the collagen in tissue samples.

The dye methyl blue can also be used to stain collagen and immunohistochemical stains are available if required.

The best stain for use in differentiating collagen from other fibers is Masson's trichrome stain.

Synthesis

Amino acids

Collagen has an unusual amino acid composition and sequence:

• Glycine (Gly) is found at almost every third residue
• Proline (Pro) makes up about 9% of collagen
• Collagen contains two uncommon derivative amino acids not directly inserted during translation. These amino acids are found at specific locations relative to glycine and are modified post-translationally by different enzymes, both of which require vitamin C as a cofactor.
  • Hydroxyproline (Hyp), derived from proline.
  • Hydroxylysine, derived from lysine. Depending on the type of collagen, varying numbers of hydroxylysines have disaccharides attached to them.

Cortisol stimulates degradation of amino acid from skin collagen.^[33]

Collagen I formation

Most collagen forms in a similar manner, but the following process is typical for type I:

1. Inside the cell
   1. Three peptide chains are formed (2 alpha-1 and 1 alpha-2 chain) in ribosomes along the Rough Endoplasmic Reticulum (RER). These peptide chains (known as preprocollagen) have registration peptides on each end; and a signal peptide is also attached to each
   2. Peptide chains are sent into the lumen of the RER
   3. Signal Peptides are cleaved inside the RER and the chains are now known as procollagen
   4. Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on Ascorbic Acid (Vitamin C) as a cofactor
   5. Glycosylation of specific hydroxylated amino acid occurs
   6. Triple helical structure is formed inside the RER
   7. Procollagen is shipped to the golgi apparatus, where it is packaged and secreted by exocytosis
2. Outside the cell
   1. Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.
   2. Multiple tropocollagen molecules form collagen fibrils, and multiple collagen fibrils form into collagen fibers
   3. Collagen is attached to cell membranes via several types of protein, including fibronectin and integrin.

Synthetic pathogenesis

Vitamin C deficiency causes scurvy, a serious and painful disease in which defective collagen prevents the formation of strong connective tissue. Gums deteriorate and bleed, with loss of teeth; skin discolors, and wounds do not heal. Prior to the eighteenth century, this condition was notorious among long duration military, particularly naval, expeditions during which participants were deprived of foods containing Vitamin C. In the human body, a malfunction of the immune system, called an autoimmune disease, results in an immune response in which healthy collagen fibers are systematically destroyed with inflammation of surrounding tissues. The resulting disease processes are called Lupus erythematosus, and rheumatoid arthritis, or collagen tissue disorders.^[34]

Many bacteria and viruses have virulence factors which destroy collagen or interfere with its production.

Fossil record

Because the synthesis of collagen requires a high level of atmospheric oxygen, complex animals may not have been able to evolve until the atmosphere was oxygenic enough for collagen synthesis.^[35] The origin of collagen may have allowed cuticle, shell and muscle formation. However, the preservation of collagen in the fossil record is very scarce.^[36] There is mounting evidence—which remains controversial—that collagen has been preserved in dinosaur specimens dated as long ago as 80 million years ago.^[37]

Art

Julian Voss-Andreae has created sculptures based on the collagen structure out of bamboo and stainless steel. His piece "Unravelling Collagen" is, according to the artist, a "metaphor for aging and growth"^[38][39].

See also

• Animal glue
• Collagenase, the enzyme involved in collagen breakdown and remodelling. For more on other proteases that target collagen see The Proteolysis Map
• Ehlers-Danlos Syndrome
• Fibrous protein
• Gelatine
• Hypermobility Syndrome
• LOXL1
• LOXL2
• LOXL3
• LOXL4
• Marfan Syndrome
• Osteoid

References

1. ^ Gloria A. Di LulloDagger , Shawn M. Sweeney, Jarmo Körkkö, Leena Ala-Kokko, and James D. San Antonio; Mapping the Ligand-binding Sites and Disease-associated Mutations on the Most Abundant Protein in the Human, Type I Collagen; J. Biol. Chem., Vol. 277, Issue 6, 4223-4231, February 8, 2002
2. ^ Muller, Werner E.G. The Origin of Metazoan Complexity: Porifera as Integrated Animals. Integrated Computational Biology, 43:3–10, 2003.
3. ^ Sikorski, Zdzisław E. (2001) Chemical and Functional Properties of Food Proteins. CRC Press. p. 242
4. ^ Gelatin's Advantages: Health, Nutrition and Safety
5. ^ Oldest Glue Discovered
6. ^ Ann Thorac Surg. 1994 Jun; 57(6): 1622–7
7. ^ Hydrolyzed Collagen pills usages
8. ^ http://www.articlesbase.com/skin-care-articles/can-collagen-be-absorbed-into-the-skin-or-is-it-all-just-one-big-hoax-674325.html
9. ^ Observe these structural aspect from a 3D perspective at http://www.messiah.edu/molscilab/Jmol/collagen/collagen_index.htm
10. ^ Wyckoff, R., R. Corey, and J. Biscoe, X-ray reflections of long spacing from tendon. Science, 1935. 82: p. 175–176.
11. ^ Clark, G., Parker, E., Schaad, J. and Warren, W.J, New measurements of previously unknown large interplaner spaceings in natural materials. J. Amer. Chem. Soc, 1935. 57: p. 1509–1509.
12. ^ GNR — A Tribute - Resonance - October 2001
13. ^ http://www.proteinscience.org/cgi/reprint/10/8/1689.pdf
14. ^ G.N. Ramachandran - Nature Structural & Molecular Biology
15. ^ Fraser, R.D., T.P. MacRae, and E. Suzuki, Chain conformation in the collagen molecule. J Mol Biol, 1979. 129(3): p. 463–81
16. ^ Okuyama, K., et al., Crystal and molecular structure of a collagen-like polypeptide (Pro-Pro-Gly)10. J Mol Biol, 1981. 152(2): p. 427–43.
17. ^ Traub, W., A. Yonath, and D.M. Segal, On the molecular structure of collagen. Nature, 1969. 221(5184): p. 914–7.
18. ^ Bella, J., M. Eaton, B. Brodsky, and H.M. Berman, Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. Science, 1994. 266(5182): p. 75–81.
19. ^ Hulmes, D.J. and A. Miller, Quasi-hexagonal molecular packing in collagen fibrils. Nature, 1979. 282(5741): p. 878–80.
20. ^ Jesior, J.C., A. Miller, and C. Berthet-Colominas, Crystalline three-dimensional packing is general characteristic of type I collagen fibrils. FEBS Lett, 1980. 113(2): p. 238–40.
21. ^ Fraser, R.D.B. and T.P. MacRae, Unit cell and molecular connectivity in tendon collagen. Int. J. Biol. Macromol., 1981. 3: p. 193–200.
22. ^ Fraser, R.D., T.P. MacRae, and A. Miller, Molecular packing in type I collagen fibrils. J Mol Biol, 1987. 193(1): p. 115–25.
23. ^ Wess, T.J., et al., Molecular packing of type I collagen in tendon. J Mol Biol, 1998. 275(2): p. 255–67.
24. ^ ^{a b c} Orgel, J.P., et al., "Microfibrillar structure of type I collagen in situ". Proc Natl Acad Sci U S A, 2006. 103(24): p. 9001–5.
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39. ^ Interview with J. Voss-Andreae "Seeing Below the Surface" in Seed Magazine

External links

• The Collagen Protein
• 12 types of collagen
• Database of type I and type III collagen mutations
• Science.dirbix Collagen
• Hydrolyzed Collagen
• Collagen Stability Calculator
• Computer-generated animations of the assembly of Type I and Type IV Collagens
• Integrin-Collagen interface, PMAP (The Proteolysis Map)—animation
• Integrin-Collagen binding model, PMAP (The Proteolysis Map)—animation
• Collagen-Integrin atomic detail, PMAP (The Proteolysis Map)—animation

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