APA ITU KOLAGEN? Kolagen merupakan kelompok protein yang terjadi secara alami.
Di alam, itu ditemukan secara eksklusif pada hewan, terutama di jaringan ikat daging dan mamalia. Ini adalah komponen utama dari jaringan ikat, dan merupakan protein yang paling melimpah pada mamalia, membuat naik sekitar 25% sampai 35% dari konten -seluruh tubuh protein.
Kolagen, dalam bentuk fibril memanjang, kebanyakan ditemukan di jaringan berserat seperti t endon, ligamen dan kulit, dan juga melimpah di kornea, tulang rawan , tulang, pembuluh darah, usus, dan cakram intervertebralis.
Dalam jaringan otot berfungsi sebagai komponen utama endomisium.
Kolagen merupakan 1% sampai 2% dari jaringan otot, dan menyumbang 6% dari berat kuat, otot tendon. Gelatin, yang digunakan dalam makanan dan industri, adalah kolagen yang telah ireversibel terhidrolisis. Image of collagen fibrils Sebuah gambar atom-force-mikroskop fibril kolagen dalam serat kolagen. Gambar Kredit: UChicago Argonne LLC
Struktur molekul dan kemasan dari kolagen telah lolos dari para ilmuwan selama beberapa de kade penelitian. Bukti pertama bahwa ia memiliki struktur yang teratur pada tingkat molekuler disajikan pada pertengahan tahun 1930-an.
Sejak saat itu banyak tokoh ulama, termasuk pemenang Hadiah Nobel C rick, Pauling, Kaya dan Yonath dan lain-lain termasuk Brodsky, Berman, dan Ramachandran, berkonsentrasi pada konformasi dari monomer kolagen.
Bersaing model beberapa, meskipun dengan benar berurusan dengan konformasi dari setiap rantai peptida individu, memberi jalan untuk model triple-heliks "Madras" yang disediakan model dasarnya benar struktur kuaterner molekul walaupun model ini masih diperlukan beberapa perbaikan.
Struktur kolagen kemasan belum ditetapkan ke tingkat yang sama di luar jenis kolagen fibrillar, meskipun telah lama dikenal heksagonal ... atau kuasi-heksagonal.
Seperti dengan struktur monomer nya, model bertentangan beberapa menuduh bahwa baik pengaturan kemasan dari molekul kolagen adalah 'lembaran-seperti' atau microfibrillar. Struktur microfibrillar fibril kolagen pada tendon, kornea dan tulang rawan telah langsung dicitrakan dengan mikroskop elektron.
Pada tahun 2006, itu menegaskan bahwa struktur microfibrillar tendon dewasa sepert i yang dijelaskan oleh Fraser, Miller, Wess (antara lain) yang paling dekat dengan struktur yang diamati, meskipun terlalu disederhanakan perkembangan topologi molekul kolagen tetangga dan karenanya tidak memprediksi konformasi yang benar dari pengaturan D-periodik terputus pentameric disebut hanya: yang mikrofibril.
Kolagen adalah sejenis protein. Berserat di alam, menghubungkan dan mendukung jaringan tubuh lainnya, seperti kulit, tulang, tendon , otot, dan tulang rawan . Ini juga mendukung organ-organ internal dan bahkan hadir dalam gigi. Ada lebih dari 25 je nis kolagen yang secara alamiah terjadi dalam tubuh.
Kolagen adalah salah satu protein yang paling banyak hadir dalam tubuh mamalia, termasuk manusia. Bahkan, itu membuat sekitar 25 persen dari jumlah total protein dalam tubuh. Beberapa orang menyebut kolagen sebagai lem yang memegang tubuh bersama-sama. Tanpa itu, tubuh akan, secara harfiah, berantakan.
Memiliki kekuatan tarik yang besar, kolagen berfungsi dengan cara yang sangat berbeda dari jenis lain dari protein. Sebagai contoh, dapat ditemukan baik di dalam dan di luar sel. Serat kolagen yang penting untuk berkontribusi dalam struktur eksternal dari sel. Namun, mereka yang hadir pada bagian dalam beberapa sel juga.
Kolagen karya tangan-di-tangan dengan elastin dalam mendukung jaringan-jaringan tubuh. Pada dasarnya, memberikan bentuk jaringan tubuh dan memberikan ketegasan dan kekuatan, elastin memberikan jaringan tubuh yang sama banyak membutuhkan fleksibilitas. Kombinasi kolagen dan
elastin sangat penting di banyak bagian tubuh, termasuk, namun tidak terbatas pada, paru-paru, tulang, dan tendon. Bahkan pembuluh darah bergantung pada kedua kolagen dan elastin.
Seringkali, kolagen dibahas dalam kaitannya dengan kulit. Ia bekerja dengan keratin untuk menyediakan kulit dengan kekuatan, fleksibilitas, dan ketahanan. Seiring bertambahnya usia, bagaimanapun, degradasi kolagen terjadi, yang menyebabkan keriput . Dengan demikian, itu adalah zat penting bagi mereka yang mencari cara untuk melawan efek penuaan pada kulit. Beberapa profesional perawatan kulit sebenarnya menyarankan orang tentang cara-cara untuk merangsang produksi kolagen dalam sel kulit.
Selain menjadi begitu penting dalam tubuh, kolagen juga memiliki banyak keperluan medis. Hal ini digunakan dalam beberapa bedah kosmetik prosedur dan dijual sebagai suplemen diciptakan untuk mobilitas sendi. Hal ini bahkan digunakan dalam merawat dan mengelola luka bakar yang serius. Untuk tujuan ini, digunakan dalam menciptakan buatan pengganti kulit.
Karena kolagen sangat penting dalam tubuh, maka bisa dipastikan bahwa kekurangan kolagen bisa menimbulkan masalah. Bahkan, ada beberapa penyakit genetik yang berhubungan dengan kekurangan kolagen. Misalnya, osteogenesis imperfecta, sering disebut sebagai penyakit tulang rapuh , hasil dari tingkat signifikan penurunan kolagen. Hal ini juga dapat terjadi akibat adanya kolagen yang berkualitas lebih rendah dari normal.
Collagen is a type of protein. Fibrous in nature, it connects and supports other bodily tissues, such as skin, bone, tendons, muscles, and cartilage. It also supports the internal organs and is even present in teeth. There are more than 25 types of collagens that naturally occur in the body.
Collagen is one of the most plentiful proteins pre sent in the bodies of mammals, including humans. In fact, it makes up about 25 percent of the total amount of proteins in the body. Some people refer to collagen as the glue that holds the body together. Without it, the body would, quite liter ally, fall apart.
Possessing great tensile strength, collagen functions in a manner that is very different from many other types of proteins. For example, it can be found both inside and outside of cells. Collagen fibers are important in contributing to the external structure of cells. However, they are present on the inside of some cells as well.
Collagen works hand-in- hand with elastin in supporting the body’s tissues. Basically, it gives body tissues form and provides firmness and strength; elastin gives the same body t issues much need flexibility. This combination of collagen and elastin is very important in many parts of the body, including, but not limited to, the lungs, bones, and te ndons. Even the blood vessels rely on both collagen and elastin.
Often, collagen is discussed in relation to the skin. It works with keratin to provide the skin with strength, flexibility, and resilience. As people age, however, collagen degradation occurs, leading to wrinkles. As such, it is an important substance for those looking for ways to fight the visible effe cts of aging on the skin. Some skincare professionals actually advise people on ways to stimulate the production of collagen in skin cells.
In addition to being so important in the body, collagen also has many medical uses. It is used in some cosmetic surgery procedures and is sold as a supplement created for joint mobility. It is even used in treating and managing serious burns. For this purpose, it is used in creating man-made skin substitutes.
Since collagens are so important within the body, it stands to reason that collagen deficiencies can be problematic. In fact, there are some genetic diseases that are associated with collagen deficiencies. For example, osteogenesis imperfecta, commonly referred to as brittle bone disease, results from a significantly decreased level of collagen. It can also result from the presence of collagen that is of lower quality than normal.
Molecular structure
The tropocollagen or collagen molecule is a subunit of larger collagen aggregates such as fibrils. At approximately 300 nm long and 1.5 nm in diameter, it is made up of three polypeptide strands (called alpha peptides, see step 2), 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 lefthanded 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 supersuper-coil referred to as the collagen microfibril. Each microfibril is interdigitated with its neighboring microfibrils to a degree that might suggest they are individually unstable, although within collagen fibrils, they are so well ordered as to be crystalline.
A distinctive feature of collagen is t he regular arrangement of amino acids in each of the three chains of these collagen subunits. The sequence often follows the pattern G ly-Pro-X or Gly-X-Hyp, where X may be any of various other amino acid residues.[23] Proline or hydroxyproline constitute about 1/6 of the total sequence. With glycine accounting for the 1/3 of the sequence, this means approximately half of t he collagen sequence is not glycine, proline or hydroxyproline, a fact often missed due to the distraction of the unusual GX1X2 character of collagen alpha-peptides. The high glycine content of collagen is important with respect to stabilization of the collagen helix as this allows the very close association of the collagen fibers within the molecule, facilitating hydrogen bonding and the formation of intermolecular cross-links.[23] This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk fibroin. About 75-80% of silk is (approximately) -Gly-Ala-Gly-Alawith 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 j ust a structural protein. Due to its key role in the determination of cell phenotype, cell adhesion, tissue re gulation and infrastructure, many sections of its nonproline-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 t riple 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 tr iple 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. Lower proline and hydroxyproline contents are characteristic of cold-water , but not warm-water fish; the latter tend to have similar proline and hydroxyproline contents to mammals.[23] The lower proline and hydroxproline contents of cold-water fish and other poikilotherm animals leads to their collagen having a lower thermal stability than mammalian collagen.[23] This lower thermal stability means that gelatin derived from fish collagen is not suitable for many food and industrial applications.
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 stagge red from each other by about 67 nm (a unit that is referred to as ‘D’ and changes depending upon the
hydration state of the aggregate). Each D-period contains four plus a fraction collagen molecules, 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 c ontaining only four molecules, called the "gap".[21] The triple-helices are also arranged in a hexagonal or quasihexagonal array in cross-section, in both the gap and overlap regions.[13][21]
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).[27] Larger fibrillar bundles are formed with t he 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.[26] 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 (i.e. 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 c ell-matrix communication, and how tissues are constructed in growth and re pair, and changed in development and disease.[28][29] For example using AFM –based nanoindentation it has been shown that a single collagen fibril is a heterogeneous material along its axial direction with significantly different mechanical properties in its gap and overlap regions, cor relating with its different molecular organizations in these two regions.[30]
Collagen fibrils are semicrystalline aggregates of collagen mole cules. Collagen fibers are bundles of fibrils.
Collagen fibrils/aggregates are arranged in different com binations and concentrations in various tissues to provide varying tissue properties. In bone, entire collagen triple helices lie in a parallel, stagg ered 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) Ca10(OH)2(PO4)6.[31] Type I collagen gives bone its tensile strength. Types and associated disorders
Collagen occurs in many places throughout the body. Over 90% of the collagen in the body, however, is of type one.[32]
So far, 28 types of collagen have been identified and described. The five most common types ar e:
Collagen I: skin, tendon, vascular ligature, organs, bone (main component of the o rganic part of bone) Collagen II: cartilage (main component of cartilage) Collagen III: reticulate (main component of reticular fibers), commonly found alongside type I. Collagen IV: forms bases of cell basement membrane Collagen V: cell surfaces, hair and placenta
Collagen-related diseases most commonly arise from genetic defects or nutritional deficiencies that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes involved in normal collagen production. Synthesis Action of lysyl oxidase 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 17% 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 (Hyl), derived from lysine (Lys). Depending on the type of collagen, varying numbers of hydroxylysines are glycosylated (mostly having disaccharides attached).
Cortisol stimulates degradation of (skin) collagen into amino acids.[34] Collagen I formation
Most collagen forms in a similar manner, but the following process is typical for type I:
Inside the cell Two types of peptide chains are formed during translation on ribosomes along the rough endoplasmic reticulum (RER): alpha-1 and alpha-2 chains. These peptide chains (known as preprocollagen) have registration peptides on each end and a signal peptide. Polypeptide chains are released into the lumen of the RER. Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains. Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on ascorbic acid (Vitamin C) as a co factor. Glycosylation of specific hydroxylysine residues occurs. Triple helical structure is formed inside the endoplasmic reticulum from e ach two alpha-1 chains and one alpha-2 chain. Procollagen is shipped to the Golgi apparatus, where it is packaged and secreted by e xocytosis. Outside the cell Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.
Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking (aldol reaction) by lysyl oxidase which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers. Collagen may be attached to cell mem branes via several types of protein, including fibronectin and integrin.
Synthetic pathogenesis
Vitamin C deficiency causes scurvy, a ser ious 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.
An autoimmune disease such as lupus erythematosus or rheumatoid arthritis[35] may attack he althy collagen fibers.
Many bacteria and viruses have virulence factors which destroy collagen or interfere with its production. Characteristics
Collagen is one of the long, fibrous structural proteins whose functions are quite different from those of globular proteins such as enzymes. Tough bundles of collagen called collagen fibers are a major component of the extracellular matrix that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has gre at tensile strength, and is the main component of fascia, cartilage, ligaments, tendons, bone and skin.[36][37] Along with soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging.[38][39] It strengthens blood vessels and plays a ro le in tissue development. It is present in the cornea and lens of the eye in crystalline form. Uses
Collagen has a wide variety of applications, from food to me dical. For instance, it is used in cosmetic surgery and burns surgery. It is widely used in the form of collagen casings for sausages.
If collagen is sufficiently denatured, e.g. by heating, 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. This process describes the formation of gelatin, which is used in many foods, including flavored gelatin desserts. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries.[40] 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 in the proportions that the human body requires —they are not 'complete proteins' (as defined by food science, not that they are partially structured). Manufacturers of collagen-based dietary supplements 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.[citation needed] 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 producer" and refers to the early process of boiling the skin and sinews of horses and other animals to obtain glue. Collagen adhesive was used by Egyptians about 4,000 years ago, and Native Amer icans used it in bows about 1,500 years ago. The oldest glue in the world, carbon-dated as more than 8,000 years old, was found to be collagen—used as a protective lining on rope baskets and embroidered fabrics, and to hold utensils together; also in crisscross decorations on human skulls.[41] Collagen normally converts to gelatin, but survived due to the dry conditions. Animal glues are thermoplastic, 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. Medical uses Cardiac applications This section may require cleanup to meet Wikipedia's quality standards. No cleanup reason has been specified. Please help improve this section if you can. (Decem ber 2010)
The four dense collagen valve rings, the central body of the heart and the cardiac skeleton of the heart are histologically bound to the myocardium. Collagen contribution to heart performance summarily represents an essential, unique and moving solid anchor opposed to the fluid mechanics of blood within
the heart. This structure is an imperme able firewall that excludes both blood and electrical influence (except through anatomical channels) from the upper to the lower chambers of the heart. As proof, one could posit that atrial fibrillation almost never deteriorates to ve ntricular fibrillation. Individual valvular leaflets are held in sail shape by collagen under variable pressure. Calcium deposition within collagen occurs as a natural consequence of aging. Calcium rich fixed points in an otherwise moving display of blood and muscle enable current cardiac imaging technology to ar rive at ratios essentially stating blood in cardiac input and blood out cardiac output. Specified imaging such as c alcium scoring illustrates the utility of this methodology, especially in an aging patient subject to pathology of the collagen underpinning. Type II Collagen and Rheumatoid Arthritis
According to a study[43] published in the journal Science, oral administration of type II collagen improves symptoms of rheumatoid arthritis. The authors conducted a randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis. A de crease in the number of swollen joints and tender joints occurred in subjects fed with chicken type II collagen for 3 months, but not in those that received a placebo. Four patients in the collagen group had complete remission of t he disease. No side effects were evident. Cosmetic surgery
Collagen has been widely used in cosmetic sur gery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic and surgical purposes. Both human and bovine collagen is widely used as dermal fillers for treatment of wrinkles and skin aging.[39] Some points of interest are:
when used cosmetically, there is a c hance of allergic reactions causing prolonged redness; however, this can be virtually eliminated by simple and inconspicuous patch testing prior to cosmetic use, and 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. porcine (pig) tissue is also widely used for producing collagen sheet for a variety of surgical purposes. alternatives using the patient's own fat, hyaluronic acid or polyacrylamide gels which are r eadily available.
Reconstructive surgical uses
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 com bination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances.
Collagen is also sold as a pill commercially as a joint mobility supplement with poor references. 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.
Collagen is also frequently used in scientific research applications for ce ll culture, studying cell behavior and cellular interactions with the extracellular e nvironment.[44] Suppliers such as Trevigen manufacture rat and bovine Collagen I and mouse Collagen IV. Wound care management uses
Collagen is one of the body’s key natural resources and a component of skin tissue that can benefit all
stages of the wound healing process. When co llagen is made available to the wound bed, closure can occur. Wound deterioration, followed sometimes by procedures such as amputation, can thus be avoided.
Throughout the 4 phases of wound healing, collagen performs the following functions in wound healing: • Guiding Function: Collagen fibers serve to guide fibroblasts. Fibroblasts migrate along a connective tissue matrix. • Chemotactic Properties: The large surface area available on collagen fibers can attract fibrogenic cells which help in healing. • Nucleation: Collagen, in the presence of certain neutral salt
molecules can act as a nucleating age nt causing formation of fibrillar structures. A collagen wound dressing might serve as a guide for orienting new collagen deposition and capillary growth. • Hemostatic properties: Blood platelets interact with the collagen to make a hemostatic plug.
Suppliers such as Human BioSciences manufacture bovine type 1 collagen into wound care bandages.
Paleontology and Archaeology
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.[45] The origin of collagen may have allowed cuticle, shell and muscle fo rmation. However, the preservation of collagen in the fossil record is ver y scarce.[46] There is mounting evidence—which remains controversial—that collagen has been preserved in dinosaur specimens dated as long ago as 80 million years ago.[47]
Also worth noting are the actinofibrils, collagen fibers present on the wings of pterosaurs.
Collagen is regularly extracted from t he bones of prehistoric animals for use in radiocarbon dating and stable isotope analysis. The integrity of the molecule can be assessed with a number of measurements (collagen yield, C:N ratio, %C and %N).[23] With re spect to radiometric dating, extracted collagen produces a 'more pure' form of carbon that can be dated than does bulk bone, which contains a high amount of carbonated apatite, which is prone to exchange with environmental sources of carbon, causing contamination. Stable isotope analysis of carbon and nitrogen are commonly used to study diet in past populations of humans, as well as to reconstruct ecological conditions.
