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Extracellular Matrix / Mast cell / Mitochondria / Methylation Connection

Discussion in 'General ME/CFS Discussion' started by Radio, Feb 20, 2014.

  1. Radio

    Radio *****

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    http://en.wikipedia.org/wiki/Extracellular_matrix

    In biology, the extracellular matrix (ECM) is the extracellular part of multicellular structure (e.g., organisms, tissues, biofilms) that typically provides structural and biochemical support to the surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

    The animal extracellular matrix includes the interstitial matrix and the basement membrane Interstitial matrix is present between various animal cells (i.e., in the intercellular spaces). Gels of polysaccharides and fibrous proteins fill the interstitial space and act as a compression buffer against the stress placed on the ECM.[4][page needed] Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest.

    The plant ECM includes cell wall components, like cellulose, in addition to more complex signaling molecules. Some single-celled organisms adopt multicelluar biofilms in which the cells are embedded in an ECM composed primarily of extracellular polymeric substances (EPS).

    Medical applications
    Extracellular matrix cells have been found to cause regrowth and healing of tissue. In human fetuses, for example, the extracellular matrix works with stem cells to grow and regrow all parts of the human body, and fetuses can regrow anything that gets damaged in the womb. Scientists have long believed that the matrix stops functioning after full development. It has been used in the past to help horses heal torn ligaments, but it is being researched further as a device for tissue regeneration in humans.

    In terms of injury repair and tissue engineering, the extracellular matrix serves two main purposes. First, it prevents the immune system from triggering from the injury and responding with inflammation and scar tissue. Next, it facilitates the surrounding cells to repair the tissue instead of forming scar tissue.

    For medical applications, the cells required are usually extracted from pig bladders, an easily accessible and relatively unused source. It is currently being used regularly to treat ulcers by closing the hole in the tissue that lines the stomach, but further research is currently being done by many universities as well as the U.S. Government for wounded soldier applications. As of early 2007, testing was being carried out on a military base in Texas. Scientists are using a powdered form on Iraq War veterans whose hands were damaged in the war.

    Not all ECM devices come from the bladder. Extracellular matrix coming from pig small intestine submucosa are being used to repair "atrial septal defects" (ASD), "patent foramen ovale" (PFO) and inguinal hernia. After one year 95% of the collagen ECM in these patches is replaced by the normal soft tissue of the heart.

    Extracellular matrix proteins are commonly used in cell culture systems to maintain stem and precursor cells in an undifferentiated state during cell culture and function to induce differentiation of epithelial, endothelial and smooth muscle cells in vitro. Extracellular matrix proteins can also be used to support 3D cell culture in vitro for modelling tumor development.

    A class of biomaterials derived from processing human or animal tissues to retain portions of the extracellular matrix are called ECM Biomaterial.
    http://en.wikipedia.org/wiki/Polysaccharide

    Nutrition polysaccharides are common sources of energy.
    Many organisms can easily break down starches into glucose, however, most organisms cannot metabolize cellulose or other polysaccharides like chitin and arabinoxylans. These carbohydrates types can be metabolized by some bacteria and protists. Ruminants and termites, for example, use microorganisms to process cellulose.

    Even though these complex carbohydrates are not very digestible, they may divour important dietary elements for humans. Called dietary fiber, these carbohydrates enhance digestion among other benefits. The main action of dietary fiber is to change the nature of the contents of the gastrointestinal tract, and to change how other nutrients and chemicals are absorbed. Soluble fiber binds to bile acids in the small intestine, making them less likely to enter the body; this in turn lowers cholesterol levels in the blood. Soluble fiber also attenuates the absorption of sugar, reduces sugar response after eating, normalizes blood lipid levels and, once fermented in the colon, produces short-chain fatty acids as byproducts with wide-ranging physiological activities (discussion below). Although insoluble fiber is associated with reduced diabetes risk, the mechanism by which this occurs is unknown.

    Not yet formally proposed as an essential macronutrient (as of 2005), dietary fiber is nevertheless regarded as important for the diet, with regulatory authorities in many developed countries recommending increases in fiber intake.

    Storage polysaccharides

    Starches are glucose polymers in which glucopyranose units are bonded by alpha-linkages. It is made up of a mixture of amylose (15–20%) and amylopectin (80–85%). Amylose consists of a linear chain of several hundred glucose molecules and Amylopectin is a branched molecule made of several thousand glucose units (every chain of 24–30 glucose units is one unit of Amylopectin). Starches are insoluble in water. They can be digested by hydrolysis, catalyzed by enzymes called amylases, which can break the alpha-linkages (glycosidic bonds). Humans and other animals have amylases, so they can digest starches. Potato, rice, wheat, and maize are major sources of starch in the human diet. The formations of starches are the ways that plants store glucose

    Glycogen
    Glycogen serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue. Glycogen is made primarily by the liver and the muscles, but can also be made by glycogenesis within the brain and stomach.

    Glycogen is the analogue of starch, a glucose polymer in plants, and is sometimes referred to as animal starch, having a similar structure to amylopectin but more extensively branched and compact than starch. Glycogen is a polymer of α(1→4) glycosidic bonds linked, with α(1→6)-linked branches. Glycogen is found in the form of granules in the cytosol/cytoplasm in many cell types, and plays an important role in the glucose cycle. Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose, but one that is less compact and more immediately available as an energy reserve than triglycerides (lipids).

    In the liver hepatocytes, glycogen can compose up to eight percent (100–120 g in an adult) of the fresh weight soon after a meal. Only the glycogen stored in the liver can be made accessible to other organs. In the muscles, glycogen is found in a low concentration of one to two percent of the muscle mass. The amount of glycogen stored in the body—especially within the muscles, liver, and red blood cells, varies with physical activity, basal metabolic rate, and eating habits such as intermittent fasting. Small amounts of glycogen are found in the kidneys, and even smaller amounts in certain glial cells in the brain and white blood cells. The uterus also stores glycogen during pregnancy, to nourish the embryo.

    Glycogen is composed of a branched chain of glucose residues. It is stored in liver and muscles.

    • It is an energy reserve for animals.
    • It is the chief form of carbohydrate stored in animal body.
    • It is insoluble in water. It turns red when mixed with iodine.
    • It also yields glucose on hydrolysis.

    ATP

    Hydrolysis is related to energy metabolism and storage. All living cells require a continual supply of energy for two main purposes: for the biosynthesis of micro and macromolecules, and for the active transport of ions and molecules across cell membranes. The energy derived from the oxidation of nutrients is not used directly but, by means of a complex and long sequence of reactions, it is channelled into a special energy-storage molecule, adenosine triphosphate (ATP). The ATP molecule contains pyrophosphate linkages (bonds formed when two phosphate units are combined together) that release energy when needed. ATP can undergo hydrolysis in two ways: the removal of terminal phosphate to form adenosine diphosphate (ADP) and inorganic phosphate, or the removal of a terminal diphosphate to yield adenosine monophosphate (AMP) and pyrophosphate. The latter usually undergoes further cleavage into its two constituent phosphates. This results in biosynthesis reactions, which usually occur in chains, that can be driven in the direction of synthesis when the phosphate bonds have undergone hydrolysis.

    Polysaccharides
    [​IMG]
    [​IMG]

    Sucrose. The glycoside bond is represented by the central oxygen atom, which holds the two monosaccharide units together.
    Monosaccharides can be linked together by glycosidic bonds, which can be cleaved by hydrolysis. Two, three, several or many monosaccharides thus linked form disaccharides, trisaccharides, oligosaccharides or polysaccharides, respectively. Enzymes that hydrolyse glycosidic bonds are called "glycoside hydrolases" or "glycosidases".

    The best-known disaccharide is sucrose (table sugar). Hydrolysis of sucrose yields glucose and fructose. Invertase is a sucrase used industrially for the hydrolysis of sucrose to so-called invert sugar. Lactase is essential for digestive hydrolysis of lactose in milk; many adult humans do not produce lactase and cannot digest the lactose in milk (not a disorder).




    Enzymatic Therapy - Better Veins?
    www.amazon.com/dp/B00014FVA4/ref=wl_it_dp_o_pC_nS_ttl?_encoding=UTF8&colid=STE6K5DNMJYK&coliid=I1KNY89BO5074C
     
    Last edited: Feb 26, 2014
  2. Allyson

    Allyson *****

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    Radio and merylg like this.
  3. Radio

    Radio *****

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    Proposed Model of the Relationships Among Changes in Expression of Extracellular Matrix and Cytoskeletal Proteins and Mitochondrial Changes in Insulin-Resistant Muscle
    Our proposed model of the relationship between inflammation and insulin resistance in skeletal muscle is shown in Fig. 5. In this model, an inflammatory response leads to changes in the extracellular matrix that are reminiscent of fibrosis. The extracellular matrix remodeling that is observed in insulin resistance may then alter mechanosignal transduction mediated by cytoskeletal elements such as intermediate (desmin) filaments or the actin cytoskeleton, resulting in altered sensing of contractile activity and ensuing gene expression changes that lead to decreased muscle fiber type I remodeling and regeneration and reduced mitochondrial number and function (perhaps mediated by changes in PGC-1α expression). Changes in sensing of contractile activity could then result in alterations in expression of cytoskeletal and structural proteins by a feedback mechanism, reinforcing this vicious cycle. Changes in these genes and proteins contribute to the mitochondrial abnormalities observed in insulin-resistant muscle and may in the end lead to decreased fat oxidation, accumulation of ectopic lipid, insulin-signaling abnormalities, and ultimately insulin resistance. We point out that this mechanism is compatible with and complementary to other current hypotheses regarding the vicious cycle connecting inflammation, mitochondrial changes, lipid accumulation, and insulin-signaling defects. The novel aspect of this mechanism is that it connects inflammatory processes with changes in insulin sensitivity by means of altered mechanosignal transduction due to fibrotic changes.

    [​IMG]

    http://ajpendo.physiology.org/content/301/5/E749
     
  4. Radio

    Radio *****

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    Fibroblasts-What-do-they-do?

    The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix. Fibroblasts secrete the precursors of all the components of the extracellular matrix, primarily the ground substance and a variety of fibres. The composition of the extracellular matrix determines the physical properties of connective tissues.

    Like other cells of connective tissue, fibroblasts are derived from primitive mesenchyme. Thus they express the intermediate filament protein vimentin, a feature used as a marker to distinguish their mesodermal origin. However, this test is not specific as epithelial cells cultured in vitro on adherent substratum may also express vimentin after some time.

    Fibroblasts-What-do-they-do
    ?
    http://www.news-medical.net/health/Fibroblasts-What-do-they-do.aspx

    Mitochondria in human disease

    http://www.ohsu.edu/nod/documents/2012/05-03/Duchen2010.pdf.
     
    Last edited: Feb 21, 2014
  5. Radio

    Radio *****

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    Thiol S-methyltransferase role in detoxication of intestinal hydrogen sulfide.

    Methylated-thiol-coenzyme M methyltransferase , mtsA (gene)) is an enzyme with system name methylated-thiol:coenzyme M methyltransferase. This enzyme catalyses the following chemical reaction

    methanethiol + coenzyme M [​IMG] methyl-CoM + hydrogen sulfide (overall reaction)
    (1a) methanethiol + [Co(I) methylated-thiol-specific corrinoid protein] [​IMG] [methyl-Co(III) methylated-thiol-specific corrinoid protein] + hydrogen sulfide
    (1b) [methyl-Co(III) methylated-thiol-specific corrinoid protein] + coenzyme M [​IMG] methyl-CoM + [Co(I) methylated-thiol-specific corrinoid protein]
    This enzyme involved in methanogenesis from methylated thiols, such as methane thiol, dimethyl sulfide, and 3-S-methylmercaptopropionate.



    Methyltransferase
    http://en.wikipedia.org/wiki/Methyltransferase
    Methylation determines fibroblast activation and fibrogenesis in the kidney
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106179/
     
    Last edited: Feb 26, 2014
  6. Allyson

    Allyson *****

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    good thread thanks @Radio

    I have been thinking about mast cells versus stretchy veins theory

    eg do mast cells make the veins stretch?

    But for anyone with varicose weins you have a vivid visual of a stretchy vein that is always dialated


    And peripheral veins are quite small - if you imagine an abdominal vein - see the size in the heart pic above - that would hold quite a lot of blood whenever you go upright.

    Ally
     
  7. Radio

    Radio *****

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    Possibly a Methyltransferase imbalance, It's crazy but all roads lead to Methyation / Gut dysfunction.
     
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  8. Xhale19991

    Xhale19991

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    What do you think about ketosis?
     
  9. Allyson

    Allyson *****

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  10. Radio

    Radio *****

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    We need glucose to fuel the Mitochondria and the Extracellular-matrix. Ketosis can be a good short term strategy to pull you out of a flare...
     
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  11. Allyson

    Allyson *****

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    yes if all else fails sugar plus caffeine works - eg the V brand energy drink - disgustingy sweet but it works - it will also keep me awake tho if I take it in the afternoon


    A
     
  12. wastwater

    wastwater Senior Member

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    uk
    Last edited: Aug 29, 2014

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