18. Metabolism of carbohydrates. Classification, digestion, transport (GLUTs, SGLUTs)..pptx

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Metabolism of carbohydrates: classification, digestion, transport (GLUTs, SGLUTs). Course: Biochemistry and Genetics Prepared by: Dr. Alisa Chebotarova, MD, PhD Modified by: Dr. I. Vyshnytska, MSc, PhD INTENDED LEARNING OBJECTIVES By the end of the lecture students must be able to: 1. Identify the...

Metabolism of carbohydrates: classification, digestion, transport (GLUTs, SGLUTs). Course: Biochemistry and Genetics Prepared by: Dr. Alisa Chebotarova, MD, PhD Modified by: Dr. I. Vyshnytska, MSc, PhD INTENDED LEARNING OBJECTIVES By the end of the lecture students must be able to: 1. Identify the major monosaccharides, disaccharides, and polysaccharides found in the human body and diet 2. Explain why ingested disaccharides and polysaccharides must be broken down into monosaccharides and describe how this is accomplished 3. Draw a diagram of how glucose is transported across intestinal epithelial cells and into the bloodstream and describe the proteins involved 4. Describe the role of glucose transporters (GLUTs) in the transport of glucose into and out of cells, and tissue specific differences in the expression and regulation of GLUTs 5. Explain the biochemical basis for the symptoms seen in lactose intolerance 6. Describe the steps of Digestion of Carbohydrates 7. Describe Absorption of Carbohydrates Alisa Chebotarova, MD, PhD Introduction • Carbohydrates are the most abundant organic molecules in nature. • They have a wide range of functions, including providing a significant fraction of the dietary calories for most organisms, acting as a storage form of energy in the body, and serving as cell membrane components that mediate some forms of intercellular communication. • Carbohydrates also serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants. Alisa Chebotarova, MD, PhD Carbohydrates – an overview • Carbohydrates are defined chemically as aldehyde or ketone derivatives of the higher polyhydric alcohols, or compounds which yield these derivatives on hydrolysis. • The empiric formula for many of the simpler carbo - hydrates is (CH2O)n, hence the name “hydrate of carbon.” Alisa Chebotarova, MD, PhD Functions of Carbohydrates 1. significant fraction of energy in the diet of most organisms • main dietary source of energy ! 2. storage form of energy in the body 3. cell membrane components that mediate some forms of intercellular communication 4. structural component of many organisms 5. precursors to many molecules Alisa Chebotarova, MD, PhD Classification • I. Simple carbohydrates (include only carbohydrate components) 1. Monosaccharides: (also called ‘simple’ sugars) are those which cannot be hydrolyzed further into simpler forms. • They can be subdivided further: (a) Depending upon the number of carbon atoms they possess, as trioses, tetroses, pentoses, hexoses, etc. (b) Depending upon whether aldehyde (– CHO) or ketone (– CO) groups are present as aldoses or ketoses. (c) Depending upon the positions of the hydroxyl groups on their asymmetric carbon atoms (D- or L-sugars, stereoisomers, or epimers) (d) Depending upon their substituents (e.g., amino sugars) 2. Disaccharides: Those sugars which yield two molecules of the same or different molecules of monosaccharide on hydrolysis. 3. Oligosaccharides: Those sugars which yield 3 to 10 monosaccharide units on hydrolysis. 4. Polysaccharides (Glycans): Those sugars which yield more than ten molecules of monosaccharides on hydrolysis. • II. Complex carbohydrates ( attached by glycosidic bonds to non-carbohydrate structures, including: 1. purine and pyrimidine bases (found in nucleic acids), 2. aromatic rings (such as those found in steroids and bilirubin) 3. proteins (found in glycoproteins and proteoglycans) 4. lipids (found in glycolipids) .asdkcnm Alisa Chebotarova, MD, PhD 1. Monosaccharides • Simple monosaccharides consist of a linear chain of three or more carbon atoms, one of which forms a carbonyl group through a double bond with oxygen • The other carbons of an unmodified monosaccharide contain hydroxyl groups • The suffix “-ose” is used in the names of sugars • NB! A carbon atom that contains four different chemical groups forms an asymmetric (or chiral) center Alisa Chebotarova, MD, PhD 1. Monosaccharides A. NUMBER OF CARBON ATOMS:✔ 3-Triose 4-Tetrose 5-Pentose 6-Hexose 7-Heptose 8-Octose 9-Nonose Alisa Chebotarova, MD, PhD B. KETOSES AND ALDOSES: ✔ If the carbonyl group is an aldehyde, the sugar is an aldose; if the carbonyl group is a ketone, the sugar is a ketose 1. Monosaccharides C. D- AND L-SUGARS (Enantiomers): • Compounds that are mirror-images of each other • Form depends on the orientation of the –H and – OH groups around the penultimate carbon (carbon atom adjacent to the terminal primary alcohol carbon) • When the – OH group on this carbon is on the right, it belongs to D-series, when the – OH group is on the left, it is a member of Lseries • NB! The vast majority of the sugars in humans are D-sugars ✔ - sugars are assumed toChebotarova, be D unless L is specifically added to the name Alisa MD, PhD 1. Monosaccharides D. STEREOISOMERS AND EPIMERS ✔ • Stereoisomers have the same chemical formula but differ in the position of the hydroxyl group on one or more of their asymmetric carbons Epimers: a special case of isomers that differ in configuration about only one ✔ asymmetric carbon (that is not the penultimate carbon-the carbon atom just adjacent to the terminal primary alcohol carbon) 1. glucose and galactose (C4) - can be interconverted in human cells by enzymes called epimerases 2. glucose and mannose (C2) Alisa Chebotarova, MD, PhD 1. Monosaccharides E. RING STRUCTURES • Monosaccharides exist in solution mainly as ring structures in which the carbonyl (aldehyde or ketone) group has reacted with a hydroxyl group in the same molecule to form a five-(Furanose) or six-membered (Pyranose) ring Carbonyl carbon - becomes a new chiral center as cyclization occurs. It is called the anomeric carbon Alisa Chebotarova, MD, PhD 1. Monosaccharides E. RING STRUCTURES • Cyclic structure has 2 possible forms (called anomers) • Based on the position of the -OH group attached to the anomeric C • Simply put: • When –OH group is below the ring =  -anomeric form ✔ • When –OH group is above the ring =  -anomeric form ✔ Alisa Chebotarova, MD, PhD 1. Monosaccharides F. REDUCING SUGARS: Sugars can be oxidized at the aldehyde carbon to form an acid. All monosaccharides are reducing sugars. Disaccharides with 1,4- glycosidic bond: lactose, maltose are reducing sugars. Galactose Disaccharide with 1,2- glycosidic bond fructose is a non- reducing sugars The anomeric carbon of a reducing sugar becomes oxidized in the presence of Benedict’s solution (Benedict’s reagent is reduced). A positive Benedict’s test is the formation of a red precipitate Clinical Biochemistry Clinitest ✔ Trademark for alkaline copper sulfate reagent (Benedict’s reagent) tablets used to test for reducing substances, such as sugars, in urine. The practice of periodic testing of urine for sugar in diabetic patients has been supplanted by blood glucose monitoring, which is far more accurate. A negative dipstick glucose assay and a positive reducing test suggest that some sugars other than glucose is present in the urine. These sugars galactose, lactose. Alisa Chebotarova, MD,include PhD 1. Monosaccharides G. SUBSTITUTED SUGARS Sugars frequently contain phosphate groups, amino groups, sulfate groups, or N-acetyl groups. 1. Phosphorylated and sulfated sugars: Most of the free monosaccharides within cells are phosphorylated at their terminal carbons, which prevents their transport out of the cell ✔ Alisa Chebotarova, MD, PhD 1. Monosaccharides G. SUBSTITUTED SUGARS 2. Amino Sugars a hydroxyl group is replaced by an amino group • Frequently, this amino group has been acetylated to form an Nacetylated sugar. • In complex molecules proteoglycans, many of the N-acetylated sugars also contain negatively charged sulfate groups attached to a hydroxyl group on the sugar Alisa Chebotarova, MD, PhD 1. Monosaccharides H. OXIDIZED AND REDUCED SUGARS 1. Oxidized sugars • Sugars can be oxidized at the aldehyde carbon to form an acid • change from “-ose” to “-onic acid” or “-onate” (e.g., gluconic acid) Alisa Chebotarova, MD, PhD 1. Monosaccharides H. OXIDIZED AND REDUCED SUGARS 2. Reduced sugars: • If the aldehyde of a sugar is reduced, all of the carbon atoms contain alcohol (hydroxyl) groups, and the sugar is a polyol (e.g., sorbitol) • If one of the hydroxyl groups of a sugar is reduced so that the carbon contains only hydrogen, the sugar is a deoxysugar, such as the deoxy ribose in DNA ✔ Alisa Chebotarova, MD, PhD Sorbitol pathway✔ • Sorbitol is a sugar alcohol formed from glucose by Aldose reductase. Sorbitol is formed from glucose in the nerve tissues, retina and the lens of the eyes, when the blood glucose level is elevated for a prolonged period of time (prolonged hyperglycemia) • Sorbitol formation is partly responsible for some of the chronic complications of diabetes mellitus • Galactitol is formed from galactose by Aldose reductase too, in the lens in children with untreated galactosemia – early cataract Alisa Chebotarova, MD, PhD E420 food Additive 2. Disaccharides • The hydroxyl group on the anomeric carbon of a monosaccharide can react with an -OH or an -NH group of another compound to form a glycosidic bond Disaccharides = 2 monosaccharides • formed from the condensation between the hydroxyl group of the anomeric carbon of a monosaccharide and a hydroxyl group of another monosaccharide Alisa Chebotarova, MD, PhD 2. Disaccharides 1. Lactose - milk sugar ✔ • galactose + glucose  (14) glycosidic bond • Reducing because it has 1 anomeric -OH 2. Sucrose – cane sugar or beet sugar ✔ • glucose + fructose ( 1 2) glycosidic bond • Non-Reducing because of no any anomeric -OH Alisa Chebotarova, MD, PhD 2. Disaccharides 3. Maltose - malt sugar •  (14) glycosidic linkage between 2 D-glucose molecules • Reducing because it has 1 anomeric OH 4. Cellobiose – a degradation product of cellulose • Composed of 2 molecules of glucose linked by a  (1,4) glycosidic bond • Chebotarova, notMD, exist Alisa Does PhD freely in nature 3. Oligosaccharides • 3-10 monosaccharides • frequently linked to proteins, where they play important roles in protein folding and serve as markers to target proteins for transport to the cell surface or incorporation into different subcellular organelles • Serve as markers on the surface of cells, playing important roles in cell recognition and the interactions between cells in tissues of multicellular organisms • most often found attached to polypeptides in glycoproteins and some glycolipids Alisa Chebotarova, MD, PhD 3. Oligosaccharides • with 2 broad classes: A. N-linked oligosaccharides attached to polypeptides by an Nglycosidic bond with the side chain amide group of the amino acid asparagine B. O-linked oligosaccharides attached to the side chain hydroxyl group of amino acid serine or threonine in polypeptide chains or the hydroxyl group of membrane lipids Alisa Chebotarova, MD, PhD 4. Polysaccharides • Most contain from hundreds to thousands of sugar units • May have linear structure ( eg cellulose, amylose) or may have branched structure (eg glycogen, amylopectin) • May be divided in 2 classes: * homopolysaccharides – composed of 1 type of monosaccharides: A. Starch Amylose (15-20%) – has a non-branching helical structure Amylopectin (80-85%) – consists of branched chains B. Glycogen consists of branched chains composed of glucose residues united by  (14) linkages in the chains and by  (16) linkages at the branch points * heteropolysaccharides – contain 2 or more types of monosaccharides. Often referred to as MD, glycosaminoglycans (GAGs) Alisa Chebotarova, PhD 4. Polysaccharides • A. Starch ✔ • polymer of glucose, and occurs in many plants as storage foods • Starch granules: • Appear under microscope as particles made up of concentric layers of material. • consist of two polymeric units of glucose: • Amylose - 15 to 20%; Low molecular weight; Soluble in water; Unbranched; 250-300 D-Glucose units linked by α1 → 4 linkages; • Amylopectin - 80 to 85%; Insoluble in water; can absorb water and swells up; Highly branched structure; Structure similar to glycogen; Main stem has α-1 → 4 glycoside bonds, At branch point α1 → 6 linkage • differ in molecular architecture and in certain properties insoluble in Alisa•Chebotarova, MD,cold PhD water 4. Polysaccharides • B. Glycogen ✔ • the reserve carbohydrate of the animal, hence it is called as animal starch • In higher animals, it is deposited in the liver and muscle as storage material which are readily available as immediate source of energy. • Structure is similar to amylopectin except that it has more branch points • It is a polymer of D-Glucose units • Glucose units in main stem are joined by α1→4 glucosidic linkages • Branching occurs at branch points by α1 → 6 glucosidic linkage • Because glycogen is so heavily branched, it is able to pack more glucose units together in a small space, thus it is more compact and has a greater solubility. MD, PhD Alisa Chebotarova, 4. Polysaccharides Alisa Chebotarova, MD, PhD 4. Polysaccharides • C. Cellulose • a polymer of glucose • principal structural component of the plant cell wall • made up of two molecules of D-Glucose linked together by β1 → 4 -Glucosidic linkage • very stable insoluble compound • in human beings no cellulose splitting enzyme is secreted by GI mucosa, hence it is not of any nutritional value • adds bulk to the intestinal contents (roughage) thereby stimulating peristalsis and elimination of indigestible food residues Alisa Chebotarova, MD, PhD Digestion and Absorption of Carbohydrates Dietary Carbohydrates • Carbohydrates are the largest source of calories in the average US diet and usually constitute 40% to 45% of our caloric intake • The plant starches amylopectin and amylose constitute approximately 50% to 60% of the carbohydrate calories consumed • The other major sugar found in fruits and vegetables is sucrose • Most foods derived from animals contain very little carbohydrate except for small amounts of glycogen • The major dietary carbohydrate of animal origin is lactose • Although all cells require glucose for metabolic functions, neither glucose nor other sugars are specifically required in the diet. • Glucose can be synthesized from amino acids found in dietary protein. • Fructose, galactose, xylulose, and all the other sugars required for metabolic processes in the human can be synthesized from glucose. Alisa Chebotarova, MD, PhD Dietary Carbohydrates • Dietary fiber is the portion of the diet that is resistant to digestion by human digestive enzymes • It consists principally of plant materials that are polysaccharide derivatives and lignan • Soluble • Insoluble • Certain types of soluble fiber have been associated with disease prevention • may lower blood cholesterol levels by binding bile acids • may have a beneficial effect in the diet of individuals with diabetes mellitus by slowing the rate of absorption of simple sugars and preventing high blood glucose levels after meals • may participate in inactivation of toxins in the gut Alisa Chebotarova, MD, PhD Digestion Of Dietary Carbohydrates • In the digestive tract, dietary polysaccharides and disaccharides are converted to monosaccharides by glycosidases, enzymes that hydrolyze the glycosidic bonds • exhibit some specificity for the sugar, the glycosidic bond (a- or b), and the number of saccharide units in the chain • Only monosaccharides are absorbed by the intestinal epithelial cells • Undigested carbohydrates enter the colon, where they may be fermented by bacteria Alisa Chebotarova, MD, PhD Digestion Of Dietary Carbohydrates A. Salivary and Pancreatic α-Amylase 1. Saliva contains salivary α-amylase✔ • endoglucosidase - hydrolyzes internal α -1,4-bonds between glucosyl residues at random intervals in the polysaccharide chains • shortened polysaccharide chains that are formed - αdextrins 2. Salivary α-amylase is largely inactivated by the acidity of the stomach contents 3. Secretions from the exocrine pancreas contain pancreatic α-amylase ✔ • enters the duodenum • continues to hydrolyze the starches and glycogen - α -1,4bonds • forms the disaccharide maltose, the trisaccharide maltotriose, and oligosaccharides - limit dextrins (contain one or more α -1,6-branches) • displays no activity toward the α -1,6-bond at branch points Alisa Chebotarova, MD, PhD Digestion Of Dietary Carbohydrates B. Disaccharidases of the Intestinal Brush Border Membrane • The dietary disaccharides lactose and sucrose and the products of starch digestion are converted to monosaccharides by glycosidases attached to the membrane in the brush border of absorptive cells: • Glucoamylase is an exoglucosidase that is specific for the α -1,4-bonds between glucosyl residues; • Substrates: amylose, amylopectin, glycogen, and maltose • Activity is highest in the ileum • Sucrase–isomaltase complex (Sucrase, Maltase, Isomaltase) - an exoglucosidase breaks the α -1,4-bonds and α -1-6 bonds • Substrates: sucrose, maltose, and maltotriose, limit dextrins • Works in the jejunum • 𝛃-Glycosidase complex (Lactase, Glucosyl–ceramidase) - Splits 𝛃 -glycosidic bonds • Substrates: glycolipids, lactose • Works in the jejunum Alisa Chebotarova, MD, PhD Digestion Of Dietary Carbohydrates B. Disaccharidases of the Intestinal Brush Border Membrane • For most of the world’s population, lactase activity decreases to adult levels at approximately 5 to 7 years of age • Adult hypolactasia is the normal condition for most of the world’s population (In people who are derived mainly from Western Northern Europeans, and milkdependent nomadic tribes of Saharan Africa, the levels of lactase remain at or only LACTOSE INTOLERANCE ✔ slightly below lactose infant levels throughout adulthood) Primary intolerance: Hereditary (autosomal recessive) Clinical Biochemistry deficiency of lactase, most commonly found in persons of Asian and African descent Secondary lactose intolerance: Precipitated at any age by GI disturbances such as celiac disease, colitis, or viral-induced damage to intestinal mucosa Symptoms: • vomiting, bloating, explosive and watery diarrhea, cramps, and dehydration after milk intake Caused by bacterial fermentation of lactose to a mixture of CH4, H2 and small organic acids in the colon • The acids are osmotically active → water inflow to colon → Alisa Chebotarova, MD, PhD Digestion Of Dietary Carbohydrates • A hydrogen breath test is used as a diagnostic tool for small intestine bacterial overgrowth and carbohydrate malabsorption, such as lactose intolerance; fructose and sorbitol malabsorption. • Breath hydrogen test (50 g of lactose are ingested orally → lactose is not digested but it is fermented by colon bacteria → lactic acid, short chain organic acids, methane, CO2, H2 → H2 is exhaled via the lungs • Normally, very little hydrogen is detectable in the breath, but undigested lactose produces high levels of hydrogen. The test takes about 2 to 3 hours Alisa Chebotarova, MD, PhD Absorption Of Dietary Carbohydrates • Only monosaccharides are absorbed from the intestinal lumen to blood • Main monosaccharides that result from digestion of di- and polysaccharides to be absorbed: • Glucose - 90% • GalactoseOther 10% • Fructose Secondary active transport serves for the uptake of glucose and galactose, which are transported against of concentration gradient in cotransport with Na+. Fructose is absorbed via GLUT5 on the apical membrane by facilitated diffusion. All are pumped into the plasma by GLUT2 from basal membra Alisa Chebotarova, MD, PhD Transport of carbohydrates • The glucose molecule is extremely polar and cannot diffuse through the hydrophobic phospholipid bilayer of the cell membrane • It passes the absorptive cells by binding to membranespanning transport proteins that bind the glucose molecule on one side of the membrane and release it on the opposite side • Two types of transporters transport monosaccharides through the cellular membranes: • Secondary active transporters (Na+ dependent) – SGLT 1, SGLT2 • Absorption of glucose and galactose • Facilitative diffusion transporters – GLUTs • Absorption of glucose, galactose and fructose • Transport of monosaccharides from blood to tissues Alisa Chebotarova, MD, PhD Transport of carbohydrates Absorption Of Dietary Carbohydrates A. Absorption by the Intestinal Epithelium • Facilitative diffusion transporters, and secondary active transporters are located on the luminal side of the cells • 1. Na+-dependent glucose transporters (SGLT1, SGLT2) ✔ • located on the luminal side of the absorptive cells • Secondary active transport: • transports Glucose from a low concentration in the lumen to a high concentration in the cell is by the cotransport of Na+ from a high concentration in the lumen to a low concentration in the cell • 2. GLUT 5 transporter✔ • Facilitated diffusion • Transports Fructose Alisa Chebotarova, MD, PhD Clinical Biochemistry • Galactose is absorbed through the same mechanisms Phlorizin is a structural • Also found in proximal convoluted tubules analogue of glucose, acts as a competitive inhibitor of SGLT1&2– can be used in treatment of DM Transport of carbohydrates Absorption Of Dietary Carbohydrates B. Transport of monosaccharides from enterocytes to blood: All are pumped into the plasma by GLUT2 from basal membrane into blood • GLUT 2 transporters ✔: • Facilitated diffusion – no energy is required • Glucose moves via the facilitative transporters from the high concentration inside the cell to the lower concentration in the blood without the expenditure of energy • Galactose and Fructose are transported along with glucose by this transporter Alisa Chebotarova, MD, PhD Transport of carbohydrates – Transport into Tissues • Glucose is transported into peripheral cells by GLUT transporters. • There are about 14 GLUTs with differing tissue specificity • Exist in 2 conformational states • 1) bind glucose outside cell, this induces conformational change to state • 2) glucose is released inside cell; GLUT returns to original conformation, ready to bind extracellular glucose again Alisa Chebotarova, MD, PhD Transport of carbohydrates – Transport into Tissues 1. Red blood cells • glucose transport is not rate limiting • GLUT 1 transporter ✔ • is present in extremely high concentrations - 5% of all membrane proteins • high affinity to glucose • as the blood glucose levels fall (to even the hypoglycemic level of 40 mg/dL) the supply of glucose is still adequate 2. Liver, Pancreas • GLUT 2 transporter ✔ • the Km is relatively high compared with that of other tissues • low affinity • Liver is the organ that maintains blood glucose levels, it converts glucose into other energy storage molecules only when blood glucose levels are high • Pancreas produces insulin when glucose levels in blood are high Alisa Chebotarova, MD, PhD Transport of carbohydrates – Transport into Tissues 3. Brain • GLUT1 and GLUT3 transporters ✔ • Both are of high affinity (low Km) • The GLUT3 transporter is expressed exclusively in neurons and the brain and has a very high affinity for glucose, allowing for preferential glucose uptake by these tissues during low glucose states. • The Vmax for glucose transport into the brain is only slightly higher than the rate of glucose utilization by the brain – thus the brain is very sensitive to hypoglycemia (< 54 mg/dL glucose) – light headedness, dizzyness, coma Alisa Chebotarova, MD, PhD Transport of carbohydrates – Transport into Tissues 4. Muscles, adipose cells • the transport of glucose is greatly stimulated by insulin • GLUT 4 transporter ✔ • Insulin dependent!!!! • In the presence of insulin, the number of GLUT 4 transporters increases on the cell surface • In adipose tissue, the stimulation of glucose transport across the plasma membrane by insulin increases its availability for the synthesis of fatty acids and glycerol from • In skeletal muscle, the stimulation of glucose transport by insulin increases its availability for glycolysis and glycogen synthesis Alisa Chebotarova, MD, PhD Elevated concentrations of glucose in blood stimulate release of insulin from b cells of the pancreas ✔ • Glucokinase is most important in liver and islet cells of pancreas. 1.Glucose enters beta cells via GLUT2 (low affinity) 2.Phosphorylated to glucose-6-phosphate by glucokinase (trapped in cell) 3.Glycolysis/TCA Cycle/Oxidative Phosphorylation – increased ATP levels 4.ATP-dependent Potassium channel closes 5.Membrane depolarization 6.Activation of a voltage-gated calcium channel 7.Ca2+ increases in the cell 8.Ca2+ stimulates fusion of insulin-containing exocytotic vesicles with the plasma membrane 9.Insulin is secreted through the plasma membrane Alisa Chebotarova, MD, PhD Elevated concentrations of glucose in blood stimulate release of insulin from b cells of the pancreas ✔ (K+ channels) ↑K+ Ca2+ ↑ Ca2+ (Ca2+ channels) IRS Glucose Depolarization DNA mRNA A and B chains (granules + C peptide in Golgi) Glucose Tyrosi ne kinase ATP (nucleus) GLUT4 (insulin R Tyrosine kinase)Pi Tyrosi ne kinase GLUT2 insulin Pi proinsulin (rER) mRNA preproinsulin (ribosomes) pancreatic β Alisa Chebotarova, MD, PhD C peptide Adipose and muscle GLUT 4 recruitment: Insulin and Exercise✮ • Both muscle contraction and insulin induce translocation of GLUT4 from the intracellular pool to the plasma membrane • The exercise signal are initiated by calcium release from the sarcoplasmic reticulum and AMPK (AMP dependent kinase) activation, or from autocrine- or paracrine-mediated activation of glucose transport. • This can be used for better blood glucose level control in patients with DM • During exercise skeletal muscle utilizes more glucose than when at rest. However, endurance training leads to decreased glucose utilization during sub-maximal exercise, in spite of a large increase in the total GLUT4 content associated with training Alisa Chebotarova, MD, PhD Properties of the GLUT 1 to GLUT 5 Isoforms ✔ TRANSPOR TER TISSUE DISTRIBUTION FEATURES GLUT 1 Human erythrocyte Blood–brain barrier Blood–retinal barrier Blood–placental barrier Blood–testis barrier a high-affinity glucose transport system Allow to import glucose even when plasma levels are very low (Basal uptake) GLUT 2 Liver Pancreatic b-cell Serosal surface of intestinal mucosa cells – transport of glucose, fructose and galactose Renal tubular cells (the same as above) A high-capacity, low-affinity transporter May be used as the glucose sensor in the pancreas – regulation of insulin release GLUT 3 Brain (neurons), placenta a high-affinity system (Basal uptake) GLUT 4 Adipose tissue Skeletal muscle Heart muscle Insulin-dependent Alisa Chebotarova, MD, PhD fructose GLUT5 Alisa Chebotarova, MD, PhD T1 T2 U L G Blood glucose (absorbed from gut and synthesized) G LU T4 glu gal GLUT2 fru G LU G LU glucose SGL Na+ T galactose T2 Transport of carbohydrates GL UT GL UT 1 GLU T3 4 Carbohydrates Monosaccharides Simple sugars Cn(H2O)n Oligosaccharides They cannot be further Contain 2-10 monosaccharides hydrolysed. molecules which are liberated on hydrolysis. aldoses О С Н triоses tetrоses pentоses hexоses Polysaccharides Polymers with high molecular weight. Contain 100 and more monosaccharides units which are liberated on hydrolysis. ketoses С О reducing mаltose, lаctose… Disaccharides, tri-, tetra-,penta- non-reducing sucrose… homopolysaccharides contain monosacchar. units of a single type. heteropolysaccharides possess 2 or more different type of monosacchar. units or their derivatives. Examples of aldoses and ketoses Aldose Ketose 3 carbon atoms Glyceraldehyde Dihydroxyacetone 4 carbon atoms Erythrose 5 carbon atoms Ribose Xylose Ribulose Xylulose Glucose Fructose 6 carbon atoms 7 carbon atoms 9 carbon atoms Galactose Mannose Sedoheptulose Neuraminic acid

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