womn of the bible

Home / Poetry / True Bread / Fig. of Speech / SymScript / SixDays     NOTABLE WOMEN OF THE BIBLE "Who can find a virtuous woman? for her price is far above rubies". Prov31:10 Abigail - Adah - Anna - Athaliah - Bathsheba - Deborah - Delilah - Dinah - Elisabeth - Esther - Eve - Hagar - Hannah - Herodias - Huldah - Jael - Jezebel - Joanna - Judith - Keturah - Leah - Martha - Mary - Michal - Miriam- Naamah - Naomi - Noah - Phoebe - Priscilla - Rachel - Rahab - Rebekah - Ruth - Sarah - Salome -Sapphira - Tabitha - Tamar - Vashti - Zeruiah - Zipporah

co factor of collagn

Vitamin C or L-ascorbic acid, or simply ascorbate (the anion of ascorbic acid), is an essential nutrient for humans and certain other animal species. Vitamin C refers to a number of vitamers that have vitamin C activity in animals, including ascorbic acid and its salts, and some oxidized forms of the molecule like dehydroascorbic acid. Ascorbate and ascorbic acid are both naturally present in the body when either of these is introduced into cells, since the forms interconvert according to pH.

Vitamin C is a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions that, when dysfunctional, cause the most severe symptoms of scurvy.^[1] In animals, these reactions are especially important in wound-healing and in preventing bleeding from capillaries. Ascorbate may also act as an antioxidant against oxidative stress.^[2] However, the fact that theenantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,^[3]underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific. "Ascorbate" without the letter for the enantiomeric form is always presumed to be the chemical L-ascorbate.

Ascorbate (the anion of ascorbic acid) is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms; the main exceptions are most bats, all guinea pigs, capybaras, and the Anthropoidea (i.e.,Haplorrhini, one of the two major primate suborders, consisting of tarsiers, monkeys, and humans and other apes). Ascorbate is also not synthesized by some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this vitamin causes the disease scurvy in humans

collan3

Deriving its name from the Greek word kolla, collagen is indeed a vital element that helps to keep the body functioning. Fortunately, there are a number of foods that help to support the creation of collagen within our bodies. Here are a few examples of the many different foods that provide the building blocks for the collagen production.

Soy products such as soymilk and cheese contain an element known as genistein. The presence of genistein gives soy products their collagen production qualities, as swell as helping to block enzymes that tend to break down and age the skin. Just about any soy product contains enough genistein to be helpful, including soy products that have been developed as substitutes for meat products.

Dark green vegetables are also excellent examples of foods containing collagen producing agents. Rich in Vitamin C, regular consumption of kale, spinach, collards, and asparagus helps to strengthen the body’s ability to manufacture collagen and to utilize the protein effectively.

Red fruits and vegetables also are excellent sources to up the collagen content of foods in the diet. The presence of lycopenes in these types of foods helps to act as antioxidants, which in turn increases collagen production. Try adding rep peppers, beets, and fresh or stewed tomatoes to the diet. In like manner, darker berries, such as blueberries and blackberries also help to boost the antioxidant level in the body and stimulate the production of collagen.

collagn2

Collagen

From Wikipedia, the free encyclopedia

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2010)

Tropocollagen triple helix

Collagen /ˈkɒlədʒɨn/ is the main structural protein of the various connective tissues in animals. (The name collagen comes from the Greek kolla meaning glue and suffix -gen denoting producing.^[1][2]) As the main component of connective tissue, it is the most abundant protein in mammals,^[3] making up from 25% to 35% of the whole-body protein content. Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendons, ligaments and skin, and is also abundant in corneas, cartilage, bones, blood vessels, the gut, and intervertebral discs. The fibroblast is the most common cell that creates collagen.

In muscle tissue, it serves as a major component of the endomysium. Collagen constitutes one to two percent of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles.^[4] Gelatin, which is used in food and industry, is collagen that has been irreversibly hydrolyzed.

Contents

  [hide] 

• 1 History and background
• 2 Chemistry
• 3 Synthesis
  • 3.1 Amino acids
  • 3.2 Collagen I formation
  • 3.3 Synthetic pathogenesis
• 4 Molecular structure
• 5 Types and associated disorders
• 6 Diseases
• 7 Characteristics
  • 7.1 Uses
• 8 Medical uses
  • 8.1 Cardiac applications
  • 8.2 Type II collagen and rheumatoid arthritis
  • 8.3 Hydrolyzed type II collagen and osteoarthritis
  • 8.4 Cosmetic surgery
  • 8.5 Bone grafts
  • 8.6 Tissue regeneration
  • 8.7 Reconstructive surgical uses
  • 8.8 Wound care management uses
• 9 See also
• 10 References
• 11 External links

History and background[edit]

The molecular and packing structures of collagen have eluded scientists over decades of research. The first evidence that it possesses a regular structure at the molecular level was presented in the mid-1930s.^[5][6] Since that time, many prominent scholars, including Nobel laureates Crick, Pauling, Rich and Yonath, and others, including 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 of Ramachandran, which provided an essentially correct model of the molecule's quaternary structure^[7][8][9] although this model still required some refinement. Not clear which refinement. Question:^{[10][11][12][13]} 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.^[14][15][16] As with its monomeric structure, several conflicting models alleged that either the packing arrangement of collagen molecules is 'sheet-like' or microfibrillar.^[17][18] The microfibrillar structure of collagen fibrils in tendon, cornea and cartilage has been directly imaged by electron microscopy.^[19][20][21] The microfibrillar structure of tail tendon, as described by Fraser, Miller, and Wess (amongst others), was modeled as being closest to the observed structure, although it oversimplified 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.^[22][23] Various cross linking agents like dopaquinone, embelin, potassium embelate and 5-O-methyl embelin could be developed as potential cross-linking/stabilization agents of collagen preparation and its application as wound dressing sheet in clinical applications is enhanced.^[24]

Chemistry[edit]

Collagen is composed of a triple helix, which generally consists of two identical chains (α1) and an additional chain that differs slightly in its chemical composition (α2).^[25] The amino acid composition of collagen is atypical for proteins, particularly with respect to its high hydroxyproline content. The most common motifs in the amino acid sequence of collagen are glycine-proline-X and glycine-X-hydroxyproline, where X is any amino acid other than glycine, proline or hydroxyproline. The average amino acid composition for fish and mammal skin is given.^[25]

Amino acid	Abundance in mammal skin (residues/1000)	Abundance in fish skin (residues/1000)
Glycine	329	339
Proline	126	108
Alanine	109	114
Hydroxyproline	95	67
Glutamic acid	74	76
Arginine	49	52
Aspartic acid	47	47
Serine	36	46
Lysine	29	26
Leucine	24	23
Valine	22	21
Threonine	19	26
Phenylalanine	13	14
Isoleucine	11	11
Hydroxylysine	6	8
Methionine	6	13
Histidine	5	7
Tyrosine	3	3
Cysteine	1	1
Tryptophan	0	0

Synthesis[edit]

First, a three-dimensional stranded structure is assembled, with the amino acids glycine and proline as its principal components. This is not yet collagen but its precursor, procollagen. A recent study^[which?](Murad et al., 1981) shows that vitamin C must have an important role in its synthesis. Prolonged exposure of cultures of human connective-tissue cells to ascorbate induced an eight-fold increase in the synthesis of collagen with no increase in the rate of synthesis of other proteins.^[26] Since the production of procollagen must precede the production of collagen, vitamin C must have a role in this step. The conversion involves a reaction that substitutes a hydroxyl group, -OH, for a hydrogen atom, H, in the proline residues at certain points in the polypeptide chains, converting those residues to hydroxyproline. This hydroxylation reaction organizes the chains in the conformation necessary for them to form a triple helix.^[27] The hydroxylation, next, of the residues of the amino acid lysine, transforming them to hydroxylysine, is then needed to permit the cross-linking of the triple helices into the fibers and networks of the tissues.

These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase^[28] and lysyl-hydroxylase. Vitamin C also serves with them in inducing these reactions. in this service, one molecule of vitamin C is destroyed for each H replaced by OH. ^[29] The synthesis of collagen occurs inside and outside of the cell. The formation of collagen which results in fibrillary collagen (most common form) is discussed here. Meshwork collagen, which is often involved in the formation of filtration systems, is the other form of collagen. All types of collagens are triple helices, and the differences lie in the make-up of the alpha peptides created in step 2.

1. Transcription of mRNA: About 34 genes are associated with collagen formation, each coding for a specific mRNA sequence, and typically have the "COL" prefix. The beginning of collagen synthesis begins with turning on genes which are associated with the formation of a particular alpha peptide (typically alpha 1, 2 or 3).
2. Pre-pro-peptide formation: Once the final mRNA exits from the cell nucleus and enters into the cytoplasm, it links with the ribosomal subunits and the process of translation occurs. The early/first part of the new peptide is known as the signal sequence. The signal sequence on the N-terminal of the peptide is recognized by a signal recognition particle on the endoplasmic reticulum, which will be responsible for directing the pre-pro-peptide into the endoplasmic reticulum. Therefore, once the synthesis of new peptide is finished, it goes directly into the endoplasmic reticulum for post-translational processing. It is now known as pre-pro-collagen.
3. Alpha peptide to procollagen: Three modifications of the pre-pro-peptide occur leading to the formation of the alpha peptide. Secondly, the triple helix known as procollagen is formed before being transported in a transport vesicle to the golgi apparatus. 1) The signal peptide on the N-terminal is dissolved, and the molecule is now known as propeptide (not procollagen). 2) Hydroxylation of lysines and prolines on propeptide by the enzymes 'prolyl hydroxylase' and 'lysyl hydroxylase' (to produce hydroxyproline and hydroxylysine) occurs to aid cross-linking of the alpha peptides. This enzymatic step requires vitamin C as a cofactor. In scurvy, the lack of hydroxylation of prolines and lysines causes a looser triple helix (which is formed by three alpha peptides). 3) Glycosylation occurs by adding either glucose or galactose monomers onto the hydroxy groups that were placed onto lysines, but not on prolines. From here the hydroxylated and glycosylated propeptide twists towards the left very tightly and then three propeptides will form a triple helix. It is important to remember that this molecule, now known as 'procollagen' (not propeptide) is composed of a twisted portion (center) and two loose ends on either end. At this point, the procollagen is packaged into a transfer vesicle destined for the Golgi apparatus.
4. Golgi apparatus modification: In the Golgi apparatus, the procollagen goes through one last post-translational modification before being secreted out of the cell. In this step, oligosaccharides (not monosaccharides as in step 3) are added, and then the procollagen is packaged into a secretory vesicle destined for the extracellular space.
5. Formation of tropocollagen: Once outside the cell, membrane bound enzymes known as 'collagen peptidases', remove the "loose ends" of the procollagen molecule. What is left is known as tropocollagen. Defects in this step produce one of the many collagenopathies known as Ehlers-Danlos syndrome. This step is absent when synthesizing type III, a type of fibrilar collagen.
6. Formation of the collagen fibril: 'Lysyl oxidase', an extracellular enzyme, produces the final step in the collagen synthesis pathway. This enzyme acts on lysines and hydroxylysines producing aldehyde groups, which will eventually undergo covalent bonding between tropocollagen molecules. This polymer of tropocollogen is known as a collagen fibril.

Action of lysyl oxidase

Amino acids[edit]

Collagen has an unusual amino acid composition and sequence:

• Glycine is found at almost every third residue.
• Proline 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 acofactor.
  • Hydroxyproline derived from proline
  • Hydroxylysine derived from lysine - 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.^[30]

Collagen I formation[edit]

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

1. Inside the cell
   1. Two types of alpha helices are formed during translation on ribosomes along the rough endoplasmic reticulum (RER): alpha-1 and alpha-2 helices. These form peptide chains (known as preprocollagen) have registration peptides on each end and a signal peptide.
   2. Polypeptide chains are released into the lumen of the RER.
   3. Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains.
   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 hydroxylysine residues occurs.
   6. Triple ɣ helical structure is formed inside the endoplasmic reticulum from each two alpha-1 chains and one alpha-2 chain.
   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, via covalent cross-linking (aldol reaction) by lysyl oxidase which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers.
   3. Collagen may be attached to cell membranes via several types of protein, including fibronectin and integrin.

Synthetic pathogenesis[edit]

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 18th 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^[31] may attack healthy collagen fibers.

Many bacteria and viruses secrete virulence factors, such as the enzyme collagenase, which destroys collagen or interferes with its production.

Molecular structure[edit]

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 threepolypeptide 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 left-handed helices are twisted together into a right-handed triple helix or "super helix", a cooperative quaternary structurestabilized 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 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 the regular arrangement of amino acids in each of the three chains of these collagen subunits. The sequence often follows the pattern Gly-Pro-X or Gly-X-Hyp, where X may be any of various other amino acid residues.^[25] 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 the 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.^[25] 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-Ala- with 10% serine, and elastin is rich in glycine, proline, and alanine (Ala), whose side group is a small 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 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 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. 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.^[25] 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.^[25] 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.^[32][33] In the fibrillar collagens, the molecules are staggered 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 containing only four molecules, called the "gap".^[22] The triple-helices are also arranged in a hexagonal or quasihexagonal array in cross-section, in both the gap and overlap regions.^[14][22]

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).^[34] 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.^[33] 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 cell–matrix communication, and how tissues are constructed in growth and repair, and changed in development and disease.^[35][36] 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, correlating with its different molecular organizations in these two regions.^[37]

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) Ca₁₀(OH)₂(PO₄)₆.^[38] Type I collagen gives bone its tensile strength.

Types and associated disorders[edit]

Collagen occurs in many places throughout the body.^{[citation needed]} Over 90% of the collagen in the body, however, is type I.^[39]

So far, 28 types of collagen have been identified and described. The five most common types are:

• Collagen I: skin, tendon, vascular ligature, organs, bone (main component of the organic 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 basal lamina, the epithelium-secreted layer of the 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.