Glycation (sometimes called non-enzymatic glycosylation) is the result of a sugar molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. Glycosylation is the enzymatic process that links Saccharides to produce glycans, either free or attached to Proteins and Lipids This enzymatic Fructose (also levulose or laevulose) is a simple reducing Sugar ( Monosaccharide) found in many foods and is one of the three Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins All blood sugars are reducing molecules. Blood sugar, used in a physiological context is a misnomer and misleading Glycation may occur either inside the body (endogenous glycation) or outside the body (exogenous glycation). Enzyme-controlled addition of sugars to protein or lipid molecules is termed glycosylation; glycation is a haphazard process that impairs the functioning of biomolecules, whereas glycosylation occurs at defined sites on the target molecule and is required in order for the molecule to function. Glycosylation is the enzymatic process that links Saccharides to produce glycans, either free or attached to Proteins and Lipids This enzymatic Much of the early laboratory research work on fructose glycations used inaccurate assay techniques that led to drastic underestimation of the importance of fructose in glycation[1].
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Exogenous
Exogenous, meaning outside the body, may also be referred to as dietary or pre-formed. Exogenous glycations and Advanced Glycation Endproducts (AGEs) are typically formed when sugars are cooked with proteins or fats. Temperatures over 120°C (~248°F) greatly accelerate the reactions, but lower temperatures with longer cooking times also promote their formation.
These compounds are absorbed by the body during digestion with about 30% efficiency. Browning reactions (usually Maillard type reactions) are evidence of pre-formed glycations. Indeed, sugar is often added to products such as french fries and baked goods to enhance browning. French fries ( North American English; sometimes not capitalized chips ( British English) fries or French-fried potatoes (formal Glycation may also contribute to the formation of acrylamide[2], a potential carcinogen, during cooking. The Chemical compound acrylamide (acrylic Amide) has the Chemical formula C 3 H 5 N[[Oxygen O]] The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation Until recently, it was thought that exogenous glycations and AGEs were negligible contributors to inflammation and disease states, but recent work has shown that they are important[3]. Although most of the research work has been done with reference to diabetes, these results are most likely important for all people, as exogenous AGEs are implicated in the initiation of retinal dysfunction, cardiovascular diseases, type II diabetes, and many other age-related chronic diseases.
Food manufacturers have added AGEs to foods, especially in the last 50 years, as flavor enhancers and colorants to improve appearance [4]. Foods with significant browning, caramelization, or with directly added preformed AGEs can be exceptionally high in these proinflammatory and disease initiating compounds. A very partial listing of foods with very high exogenous AGEs includes: donuts, barbecued meats, cake, and dark colored soda pop[5].
Endogenous
Endogenous glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Fructose (also levulose or laevulose) is a simple reducing Sugar ( Monosaccharide) found in many foods and is one of the three Galactose (Gal (also called brain sugar) is a type of Sugar which is less sweet than Glucose. The balance of the sugar molecules is used for metabolic processes. It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel[6]. Glycation is the first step in the evolution of these molecules through a complex series of very slow reactions in the body known as Amadori reactions, Schiff base reactions, and Maillard reactions; all lead to advanced glycation endproducts (AGEs). The Amadori rearrangement is an Organic reaction describing the acid or base catalyzed Isomerization or Rearrangement reaction of the N- Schiff base (or azomethine) named after Hugo Schiff, is a Functional group that contains a Carbon - Nitrogen Double bond The Maillard reaction is a Chemical reaction between an Amino acid and a Reducing sugar, usually requiring Heat. Some AGEs are benign, but others are more reactive than the sugars they are derived from, and are implicated in many age-related chronic diseases such as: type II diabetes mellitus (beta cell damage), cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged), Alzheimer's disease (amyloid proteins are side-products of the reactions progressing to AGEs), cancer (acrylamide and other side-products are released), peripheral neuropathy (the myelin is attacked), and other sensory losses such as deafness (due to demyelination) and blindness (mostly due to microvascular damage in the retina). Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Peripheral neuropathy is the term for damage to Nerves of the Peripheral nervous system, which may be caused either by diseases of the Nerve or from the Blindness is the condition of lacking Visual perception due to Physiological or Neurological factors This range of diseases is the result of the very basic level at which glycations interfere with molecular and cellular functioning throughout the body and the release of highly-oxidizing side-products such as hydrogen peroxide. Hydrogen peroxide (H2O2 is a very pale blue liquid which appears colorless in a dilute solution slightly more Viscous than water
Glycated substances are eliminated from the body slowly, since the renal clearance factor is only about 30%. This implies that the half-life of a glycation within the body is about double the average cell life. Red blood cells are the shortest-lived cells in the body (120 days), so the half-life is about 240 days. This fact is used in monitoring blood sugar control in diabetes by monitoring the glycated hemoglobin level. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Glycosylated (or glycated hemoglobin ( hemoglobin A1c Hb1c, or HbA1c) is a form of Hemoglobin used primarily to identify the average As a consequence, long-lived cells (such as nerves, brain cells), long-lasting proteins (such as eye crystalline and collagen), and DNA may accumulate substantial damage over time. Metabolically-active cells such as the glomeruli in the kidneys, retina cells in the eyes, and beta cells (insulin-producing) in the pancreas are also at high risk of damage. The kidneys are complicated organs that have numerous biological roles The vertebrate retina is a light sensitive part inside the inner layer of the Eye. Beta cells ( beta-cells, β-cells) are a type of cell in the Pancreas in areas called the Islets of Langerhans. The epithelial cells of the blood vessels are damaged directly by glycations, which are implicated in atherosclerosis, for example. Atherosclerotic plaque tends to accumulate at areas of high blood flow (such as the entrance to the coronary arteries) due to the increased presentation of sugar molecules, glycations and glycation end-products at these points. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro-aneurisms; this may cause strokes if in the brain.
See also
References
- ^ Ahmed N, Furth AJ. Alagebrium (formerly known as ALT-711) is a drug produced by Alteon Corporation which is currently being evaluated in clinical trials Glycosylation is the enzymatic process that links Saccharides to produce glycans, either free or attached to Proteins and Lipids This enzymatic Fructose (also levulose or laevulose) is a simple reducing Sugar ( Monosaccharide) found in many foods and is one of the three Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. "Failure of common glycation assays to detect glycation by fructose. " Clin Chem 1992;38:1301-3 PMID 1623595.
- ^ Stadler RH, Blank I, Varga N, Robert F, Hau J, Guy PA, Robert MC, Riediker S. "Acrylamide from Maillard reaction products. " Nature 2002;419:449-50. Nature is a prominent Scientific journal, first published on 4 November 1869 PMID 12368845.
- ^ Vlassara, Helen, "Advanced Glycation in Health and Disease: Role of the Modern Environment", Annals of the New York Academy of Science, 1043: 452–460 (2005). doi: 10. 1196/annals. 1333. 051
- ^ Melpomeni Peppa, et al, "Glucose, Advanced Glycation End Products, and Diabetes Complications: What Is New and What Works", Clinical Diabetes • Volume 21, Number 4, 2003
- ^ Theodore Koschinsky, et al. "Orally absorbed reactive glycation products: an environmental risk factor in diabetic nephropathy", Proceedings of the National Academy of Science, USA Vol. 94, pp. 6474–6479, June 1997
- ^ McPherson JD, Shilton BH, Walton DJ. "Role of fructose in glycation and cross-linking of proteins. " Biochemistry 1988;27:1901-7. PMID 3132203.
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