COLLAGEN BIOSYNTHESIS.pdf

COLLAGEN BIOSYNTHESIS MS AMINAH SUHAILA BIOCHEMISTRY FACULTY OF DENTISTRY  At the end of this lecture: 1. Describe the structure, types and synthesis of collagen 2. Explain the disorders of collagen and its therapeutic applications.  The mos...

COLLAGEN BIOSYNTHESIS MS AMINAH SUHAILA BIOCHEMISTRY FACULTY OF DENTISTRY  At the end of this lecture: 1. Describe the structure, types and synthesis of collagen 2. Explain the disorders of collagen and its therapeutic applications.  The most abundant protein in the body. Its fiber-like structure is used to make connective tissue. Connects other tissues It helps to make and is a major tissues strong and component of bone, resilient, able to skin, muscles, tendons, withstand stretching. and cartilage.  Background In food, collagen is naturally found only in animal flesh like meat and fish that contain connective tissue. However, a variety of both animal and plant foods contain materials for collagen production in our own bodies.  Background Our bodies gradually make less collagen as we age, but collagen production drops most quickly due to excess sun exposure, smoking, excess alcohol, and lack of sleep and exercise. With aging, collagen in the deep skin layers changes from a tightly organized network of fibers to an unorganized maze. Environmental exposures can damage collagen fibers reducing their thickness and strength, leading to wrinkles on the skin’s surface.  What does collagen do? Collagen’s main role is to provide structure, strength and support throughout your body.  Collagen’s specific roles include: 1 –Helping fibroblasts form in your dermis (middle skin layer), which helps new cells grow. –Playing a role in replacing dead skin cells. 2  3 Providing a protective covering for organs. –Giving structure, strength and elasticity to your skin 4 5 –Helping your blood to clot. Collagen Molecular Structure Triple helix structure of collagen –Individually there are three polypeptide strands. These are called alpha chains and each of them has a conformation of a left-handed helix. –Further the three left-handed helices are twisted together into a right-handed coiled coil, forming a triple helix or "super helix". The final cooperative quaternary structure stabilized by numerous hydrogen bonds. Microfibril Each of the triple helices forms a right-handed super-super-coil that is referred to as the collagen microfibril. Thereafter, each of the microfibril is interdigitated or intercalated with its neighboring microfibrils. This strengthens the structure of the individual molecules. Arrangement of amino acids in collagen –Collagen contains specific amino acids – Glycine, Proline, Hydroxyproline and Arginine. These amino acids have a regular arrangement 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. –Proline or hydroxyproline constitute about 1/6 of the total sequence. –Glycine accounts for 1/3 of the sequence meaning that approximately half of the collagen sequence is not glycine, proline or hydroxyproline. Types of Collagen  Type I Collagen 1 The superstar of the collagen family, making up approximately 90% of the body's collagen supply. It is integral to the structure of the skin, bones, tendons, fibrous cartilage, connective tissue, and teeth. Sourced from bovine or marine collagen peptides.  Type I Collagen –enhance skin health by promoting skin elasticity and hydration, thereby reducing wrinkles and dryness. –bolster the health of nails, ensuring they stay strong and less prone to breakage. They also promote healthier, thicker hair by improving hair follicle health and function. –enhance bone health by contributing to bone density and strength, helping to reduce the risk of bone disorders like osteoporosis  Type II Collagen –Cartilage is the flexible connective tissue found in many areas of the body, including the joints between bones, such as the elbows, knees, and ankles. As we age, the wear and tear on our joints can lead to discomfort and conditions like osteoarthritis. Derived from chicken bones –can help reduce joint pain, inflammation, and swelling in individuals with joint disorders improve joint flexibility and contribute to the connective tissue's overall health, providing relief from joint discomfort.  Type III Collagen –Often found alongside type I, is integral to the structure and function of our skin, blood vessels, and organs. –Derived from bovine sources can promote cardiovascular health by strengthening the blood vessels aids in maintaining the structure of the muscle fibres  Type IV Collagen –A less well-known collagen type, performs an essential function as a filter in the skin layers, forming a barrier between the skin and internal organs. This helps to prevent toxins and other substances from moving from the organs into the skin. Derived from egg whites and shell membranes can significantly boost skin health and aid wound healing –helps to filter waste products and prevent kidney damage.  Type V Collagen –Plays an essential role in the health of our hair and cell surfaces. It contributes to the strength and thickness of hair strands, promoting healthy hair growth. –Plays a structural role in the matrix of bones, in skin cells, and the matrix of muscles, liver, lungs and placenta. Synthesis of Collagen  Within the cell 1. During translation, two types of peptide chains are formed on ribosomes along the rough endoplasmic reticulum (RER). These are called the alpha-1 and alpha-2 chains. These peptide chains (known as preprocollagen) have registration peptides on each end and a signal peptide. 2.The preprocollagen is then released into the lumen of the RER. Thereafter the signal peptides are cleaved inside the RER and the peptide chains are now called pro-alpha chains.  Within the cell 3.Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on ascorbic acid (Vitamin C) as a cofactor. Further glycosylation of specific hydroxylysine residues occurs. 4.Triple helical structure is formed inside the endoplasmic reticulum from each two alpha-1 chains and one alpha-2 chain. This is called procollagen. 5.Procollagen is transported into the golgi apparatus, where it is packaged and secreted by exocytosis.  Outside the cell 1.Once outside the cell, the registration peptides are cleaved and tropocollagen is formed by procollagen peptidase. 2.These tropocollagen molecules gather to form collagen fibrils, via covalent cross-linking 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. Diseases related with collagen Osteogenesis imperfecta – Caused by a mutation in type 1 collagen, dominant autosomal disorder, results in weak bones and irregular connective tissue, some cases can be mild while others can be lethal, mild cases have lowered levels of collagen type 1 while severe cases have structural defects in collagen. Chondrodysplasias – Skeletal disorder believed to be caused by a mutation in type 2 collagen, Ehlers-Danlos Syndrome – is a condition that affects the connective tissues in your body including cartilage, bones, blood and fat. -Some rare types of Ehlers-Danlos syndrome can cause fatal complications — especially vascular Ehlers-Danlos syndrome (EDS that affects your blood vessels). -A genetic mutation causes Ehlers-Danlos syndrome. Genetic mutations are changes to your DNA sequence that happen during cell division when your cells make copies of themselves. Alport syndrome - a genetic condition in which kidneys don’t produce normal type IV collagen proteins. - can be passed on genetically, usually as X-linked dominant, but also as both an autosomal dominant and autosomal recessive disorder, sufferers have problems with their kidneys and eyes, loss of hearing can also develop in during the childhood or adolescent years. Osteoporosis - A progressive bone disease characterized by reduced bone density and increased risk of fractures. It occurs when the body loses too much bone or makes too little bone, resulting in weakened and porous bones. -Collagen forms a scaffold upon which calcium and other minerals are deposited, contributing to bone density and hardness.  Why Use Collagen Biomaterials for Regenerative Medicine? Collagen-based biomaterials have a large range of applications both in vivo and in vitro. Excellent biocompatibility due to weak antigenicity and safety due to biodegradability, makes collagen a primary resource in medical applications.  Bone Orthopaedic graft substitutes & Cartilage Sports repair Tendon Medicine repair Bone graft substitutes Dental Dental membranes Dental plugs  Collagen dressings and powder Flowable Wound Care Scaffolds Skin substitutes Wound and burn grafts Vascular grafts Cardiovascular Vascular closure devices  Dermal fillers General, Suture Plastic & line reinforcement Reconstructive Hernia repair Surgery Breast reconstruction Ophthalmic Other Oncology Faizal Halim - Malaysian footballer got acid attack Thank You