Collagen
Collagen ( tropocollagen precursor; internationalized notation collagen; emphasis on the last syllable ) is only in multicellular organisms ( including humans), mainly occurring structural protein of the connective tissue (more precisely, of the extracellular matrix). In the human body, collagen is the most frequently occurring protein with over 30 % share of the total mass of all proteins. It is an important organic part of the connective tissue (bones, teeth, cartilage, tendons, ligaments ) and the skin. The name was inspired collagen (from the Greek: glue -causing) originally due to its former use as bone glue in wood crafts. It is the main raw material for the production of gelatin.
Collagen consists of single, long collagen molecules (protein chains) that form (similar to the polyproline - II helix ) a left-handed helix. Three of these helices are then arranged in a right-handed superhelix, which are stabilized by hydrogen bonds with each other. A striking feature of the primary structure ( amino acid sequence) of collagen is that every third amino acid is glycine. A frequently repeated in the protein family of collagens sequence motif is glycine -proline- hydroxyproline.
Collagen fibers have enormous tensile strength and are hardly extensible. The tight winding is crucial for the high tensile strength of collagen fibers: they can withstand tensions up to ten thousand times their own weight record.
Collagens play a crucial role in the biomineralization of vertebrates.
In common parlance, collagen type I is equated with " collagen ". Collagen type I, although quantitatively the most important in the mammalian collagen and also the most famous by its use as gelatin, but there are other types of collagen, the structural differ significantly from type I collagen and perform other important biological functions. Gelatin is the denatured form of fibrillar collagen type I, II and / or III and is usually obtained from slaughterhouse waste. It should be noted that collagen type II occur mainly in cartilage, mixtures of collagen type I and III are taken from tendons, ligaments and skin.
- 3.1 translation
- 3.2 hydroxylation
- 3.3 triple helix
- 3.4 glycosylation
- 3.5 exocytosis
- 3.6 Prokollagenpeptidasen
- 3.7 fibrillogenesis
- 3.8 Cross-linking
- 3.9 collagen fibers
- 4.1 Structure of type I collagen
- 5.1 Nutrition and Linings
- 5.2 pharmaceuticals
- 5.3 Cosmetics
- 5.4 technology
Occurrence
Functional genes collagenous structural proteins are found in all the tribes of the multicellular animals, in sponges, cnidarians to mammals, mainly in the extracellular matrix and in connective tissue. Collagens do not occur in other organisms such as fungi, plants and protozoa.
Construction
Collagen molecule
The polypeptide chains of collagen are individually synthesized by the ribosomes of the rough endoplasmic reticulum. The collagen molecule or triple helical tropocollagen only molecules of the extracellular matrix (ECM ) are known. They have in common that they are composed of three polypeptide chains. These are each in left-handed collagen helices ( α - chains, not to be confused with the α helices rechtsgänginen ) and are common in the form of the characteristic right-handed triple helix wrapped around each other (see picture right). Each collagen helix can be composed depending on the type of collagen amino acids 600 to 3000 and is equipped with large domains of repeating itself ( repetitive ) GXY sequences are constructed.
Thus is located at every third position is a glycine (G ) residue. Glycine as the smallest amino acid fits perfectly into the triple helix with its very tight turns. The amino acid proline is very common to find X at position. Proline functions here due to its rigid ring structure as a "corner" in the polypeptide chain and supports the training of tight turns within the triple helix. 4-hydroxyproline is predominantly localized at position Y and stabilizes the triple helix via hydrogen bonds between adjacent polypeptide chains. By the use of glycine, proline and hydroxyproline, the rotation of the polypeptide is defined and supported the narrow space conditions in the triple helix into account.
The presence of hydroxylysine next hydroxyproline is also characteristic of collagen. Hydroxylysine is a prerequisite for the formation of covalent cross-links, thus the individual triple helices can be fixed in space within the collagen fibrils.
Collagen fibril
In the fibrils adjacent collagen molecules are not arranged flush, but about 67 nm, ie,, offset from each other by about one- fifth of its length. This arrangement has the consequence that on electron micrographs of metal - contrasted a collagen cross-striations can be seen. The result is a characteristic banding pattern which is all 67 nm ( 234 amino acids ) are repeated and designated as D period. Characterized the α - chains are divided into four homologous regions D1-D4. The bands occurring in a D unit are denoted by ae. Collagen fibrils are ordered polymers, which can be many microns in length in the mature tissue. They are often too large, cable-like bundles of collagen fibers are grouped. In tendons, the collagen type I fibril diameter 50-500 nm amounted, in the skin 40-100 nm and in the cornea ( cornea ) 25 nm fibrillogenesis of collagen is often regulated by small leucine-rich proteoglycans, so that in the corresponding tissues fibrils can occur with a defined diameter and defined arrangement.
Structure elucidation
The current appearance of the collagen triple helix and the spatial arrangement of amino acid residues and their hydrogen bonds with each other is largely due to the X-ray crystallographic work of Indian scientists GN Ramachandran and Gopinath Kartha back (1954).
Significant Enlightenment ( the entire primary structure of type I collagen as well as the macro-structures of type IV and VI) was made by the former Max Planck Institute for Protein and Leather Research in Munich (1956 to clarify the connective tissue founded by sponsoring the leather industry ) from 1966 under the direction of Klaus Kühn (after laying Institute at the Max Planck Institute for Biochemistry in Martinsried ).
Biosynthesis
Translation
The individual collagen polypeptide chains are produced as with other Proteinbiosynthesen on the rough endoplasmic reticulum, where they enter the lumen of the endoplasmic reticulum. They arise in the form of larger precursor molecules, the pro- α - chains, which are equipped with N- and C-terminal propeptides.
Hydroxylation
Arising in the endoplasmic reticulum, or polypeptide of any existing OH groups to individual proline and lysine residues attached ( hydroxylation ).
Ascorbic acid (vitamin C ) is an important cofactor in the hydroxylation of the amino acid proline to hydroxyproline by the enzyme prolyl 4- hydroxylase ( EC 1.14.11.2 ) and lysine hydroxylysine by the enzyme lysyl hydroxylase ( EC 1.14.11.4 ). Hydroxyproline comes to the function to strengthen the triple helix within a collagen molecule via hydrogen bonds between adjacent collagen polypeptide chains. Hydroxylysine serves to anchor covalent cross-links between collagen molecules. In the absence of hydroxylation only damaged collagen molecules are formed, which can not fulfill its function as a structural protein. It should be noted that nearly all of the symptoms of ascorbic acid deficiency is scurvy disease caused by failure of the collagen biosynthesis.
Triple helix formation
By the formation of disulfide bonds between the C-terminal propeptides, the triple helix formation is initiated. Three pro- α - chains form this via hydrogen bonds, a three-stranded helix molecule that procollagen.
Glycosylation
Finally, most glycosylation occurs some lysine residues by the procollagen galactosyltransferase ( EC 2.4.1.50 ) or procollagen - glucosyltransferase ( EC 2.4.1.66 ) or more glycosylation enzymes.
Exocytosis
The triple-helical collagen molecules are released in this form from the cell. The release of the molecules in the extracellular space occurs by exocytosis of secretory vesicles over what the Glycosylbestandteile appear to be involved.
Prokollagenpeptidasen
Immediately after release from the cell with the help of the propeptides are cleaved procollagen peptidases. The enzyme procollagen N- endopeptidase ( EC 3.4.24.14 ) is required for the elimination of amino-terminal sequences, while the enzyme procollagen C- endopeptidase ( EC 3.4.24.19 ) cleaves carboxy-terminal procollagen sequences.
Fibrillogenesis
After cleavage of the Prokollagenpeptide, individual collagen molecules to collagen fibrils store together ( fibrillogenesis ).
Cross-linking
After having triple helical collagen molecules, individual offset by one-fifth of its length mounted on one another, carried on covalent cross-links only to be converted related hydroxylysine, thus, the spatial arrangement is permanently fixed. The (intracellular incurred by the lysyl hydroxylase ) hydroxylysine residues are oxidized by lysyl oxidase ( EC 1.4.3.13 ) to Allysin. The two adjacent Allysinreste enter into an aldol condensation, which is fixed by a vicinity of this permanent cross-linking.
Collagen fibers
Many such covalently stabilized collagen fibrils eventually form collagen fibers, which constitute the basic structure of the extracellular matrix of all tissues animals.
Collagen types
The collagens are divided into several subgroups.
In mammals, type I collagen, a fibrillar collagen, the most common collagen type and is found in skin, tendons, fascia, bone, blood vessels, internal organs and in the dentine, while type II collagen acts as a structural protein of hyaline and elastic cartilage. Type III collagen found in vessel walls, internal organs, skin and cornea. Collagen Types IV and V are part of the basal lamina.
28 different types of collagen are known ( type I to XXVIII ) and at least ten other proteins with collagen-like domains.
The following compilation of some members of the collagen family are listed.
A cleavage product of the Collagen XVIII is endostatin with a molecular mass of 20 kDa.
Structure of type I collagen
The three collagen polypeptide chains are in the case of type I collagen, the α - chains, [ α1 (I) 2α2 (I) ], which wind around each other to form a triple helix. The gene for the α1 chain of type I collagen is composed of 50 exons, of which more than half of a length of 54 base pairs (bp ), or two to three times this length. They code for the sequence ( GXY ) 6 or a multiple thereof.
Use
Collagen is used primarily in the form of gelatin, which is derived from cattle gap, pigskin and bones of cattle and pigs.
Nutrition and feed materials
About 32,000 t of gelatin in Germany produced annually in food quality, the overall European production is 120,000 t ( 70 % pigskin, 18% bone, 10 % bovine gap, 2 % Other ) are used in Germany to about 90,000 t, of which 2/ 3 to the field of nutrition and omitted from the rest, about half the feed area.
Pharma
Approximately 15,000 tons are processed in the chemical and pharmaceutical industries. This packaging of tablets and vitamin supplements (hard and soft capsules ) and gelatin suppositories are the main areas of application in the pharmaceutical industry dar. addition, gelatin is used for hemostatic sponge and as a blood plasma substitute.
Cosmetics
Collagen is used as a drug for many years in the cosmetic application and is there mainly for the reduction of skin aging, anti -aging serve. Today collagen products are used in cosmetics in the form of creams use. The collagen used for this purpose is usually extracted from pig skin.
Technology
In analogue photography provides the basis for the gelatin photosensitive layers on the film and photo paper. Even modern printer paper for printing color images are coated with gelatin.