Carbohydrate Session 1 Slides PDF

Nutritional Advances in Practice Carbohydrates: Changing knowledge and recommendations (Session 1) Dr Andrea Peakall [email protected]...

Nutritional Advances in Practice Carbohydrates: Changing knowledge and recommendations (Session 1) Dr Andrea Peakall [email protected] R  Part 1: Introduction Plan for the session Part 2: Basic overview of sugars (supplementary discussion on sugar chemistry as a recording) A Part 3: Digestion & absorption of sugars and carbohydrates Part 4: Regulation of blood glucose & the glycaemic response NEXT WEEK – session 2 Part 5: Sources of sugars and role in foods, relation to health & disease, consumption patterns and dietary recommendations Carbohydrates: Changing knowledge and recommendations The story of carbohydrates continues elsewhere….  protein topic (low carb, keto diets)  fat topic (many links with carbohydrates  microbiome topic (non-digestible carbohydrates)  (micronutrient – role of B-vitamins)  (phytochemicals – impact on sugar absorption & metabolism) Famine relief (pre-1980s) Low vitamin D (during winter months) What links the following? Cave paintings and ancient pots ~11000-5000 BCE  ~65-75% of world’s population are lactose intolerance Milk powder sent to help with famine relief “Food chauvinism” Better to consider lactose tolerance (lactase persistence) is in fact the more unusual condition  Milk the perfect food for new born mammals Milk is produced by the mammary gland of all female mammals Milk is unique having a complete range of nutrients required for growth of infants Milk has no rival in the diversity and range of products formed from the raw material  Milk the perfect food for new born mammals  perfect isotonic balance of minerals for hydration  unique protein – casein forms “curds” in stomach which slows passage through GI tract  unique sugar – lactose balanced for use and storage  Lactose Digestion  Lactose is a di-saccharide  Made up of glucose + galactose  No transporter in the small intestine for absorption  Enzyme lactase breaks it into mono-saccharides  Glucose and galactose are absorbed by transporter  Milk the perfect food for new born mammals  Limited in iron and vitamin C  Mammals need to be weaned on to solids  Lactase no longer needed and so is down-regulated  Some humans have genetically evolved to retain lactase past weaning and into adulthood  Disaccharide Digestion  Three important dietary di-saccharide  Lactose, Sucrose and Maltose  No transporters for disaccharides for absorption  Disaccharidases convert to monosaccharides: Lactase : glucose + galactose Sucrase : glucose + fructose Maltase : glucose + glucose (& isomaltose) Nutritional Advances in Practice Part 2: Overview of sugar chemistry Carbohydrates – back to basics  Carbohydrate = hydrated (water) carbon  Monosaccharide formula = (CH2O)n, where n is 3 or more carbons; (e.g. C6H12O6) Carbohydrat es Comple Simple x Disaccharide Oligosaccharide Polysaccharide Monosaccharide (2 sugar units) (3-9 sugar units) (>10 sugar (1 sugar unit) units) Fructos Lactose Maltose Raffinose Inulin Galactos Glycogen Starch e e Sucrose Dietary Glucose fibre Monosaccharides  Classified based on number of carbon atoms  Triose (3 carbon) – e.g. glyceraldehyde  Tetrose (4 carbon) – e.g. erythrulose  Pentose (5 carbon) – e.g. ribose and arabinose  Hexose (6 carbon) – e.g. glucose, galactose and fructose Monosaccharides Monosaccharide Characteristic Glucose The main carbohydrate used by the brain; oxidised in all cells. Galactose Both galactose and fructose must be converted into Fructose glucose (or lactate) before they can be oxidised. The conversion of fructose and galactose into glucose occurs mainly in the liver at a relatively slow pace. Numbering the carbons: GLUCOSE You do not need to learn any structures Cyclic sugars: 6 5 4 1 2 3 Haworth projection You do not need to learn any structures Carbon 1: the alpha bond 4 1 α You do not need to learn any structures Maltose 1  Maltose (alpha 1-4 glycosidic bond) 1 4  Condensation synthesis reaction (dehydration)  1,4 alpha (α) or 1,4 beta (β) glycosidic bonds (α) (β)  The 1,4 alpha (α) glycosidic bonds are formed when the carbon-1 OH points down  1,4 beta (β) glycosidic bonds are formed when the carbon- 1 OH points up Different monosaccharides You do not need to learn any structure Different monosaccharides β α You do not need to learn any structure Different monosaccharides 6 2 1 4 You do not need to learn any structures  α β β 4 1 4 1 1 4 You do not need to learn any structure Disaccharide formation Combination of two monosaccharides  Condensation synthesis reaction (dehydration)  Results in glycosidic bond (a covalent bond) Oligosaccharides & Polysaccharides Oligosaccharides  are 3-9 monosaccharides combined  found in most vegetables  E.g. raffinose (3), stachyose (4), inulin (2-60) Polysaccharides  contain 10+ monosaccharides combined in one molecule, usually thousands  can be digestible or non-digestible  E.g. starch, glycogen and cellulose, as well as resistant starches Polysaccharide structure  Homopolysaccharides are composed of a single type of sugar monomer bonded to identical molecules to form a polymer E.g. Starch - made entirely of glucose monomers  Heteropolysaccharides contain two or more different monosaccharide units E.g. Heparin - made up of D-glucuronic acid, L-iduronic acid, N-sulfo-D-glucosamine Starch  Storage form for monosaccharides  Main dietary carbohydrate (bread, cereal, rice, potatoes etc)  Amylose consists of long unbranched chains of glucose residues, - connected by α-1,4 linkages  Amylopectin consists of highly branched structures - with α-1,4 linkages BUT - the branch points are α-1,6 linkages Amylopectin Glycogen  storage form of glucose within animals  similar structure to starch amylopectin; homopolysaccharides (branched glucose)  Difference between starch amylopectin and glycogen is the frequency of branches  Digestion - AMYLASE Alpha-amylase catalyses the hydrolysis of starch Only hydrolyses α-1-4 links Two enzymes: salivary α-amylase & pancreatic α-amylase  X X X X X X X Alpha-amylase is an endo-enzyme (does not work at the end of chains) and only works on α-1-4 not on α-1-6 links Cellulose  Structural components of plant cell walls  Unbranched homopolysaccharides – like amylose  Linkage is beta β1-4 glycosidic bonds Nutritional Advances in Practice Part 3: Digestion & Absorption of Sugars R Carbohydrate summary of key points so far…  Differences between some sugars appears minor – but this can have a big difference on how they behave, e.g.  glucose and galactose are virtually identical (except in one OH orientation) but are treated differently by the liver  the alpha-1,4 link is different to beta-1,4 link and is the difference between starch and cellulose  the D- form and L-form are identical mirror images – but this can be the difference between being active or not being active You do not need to know the chemistry/structures – they were to show you the importance of small changes Carbohydrate digestion summary so far…  α-Amylase will break down α-1,4 linkages in amylose, amylopectin and glycogen to give:  maltose, maltotriose, & dextrins (short chains with α-1,4 linkages)  limited-dextrins (short chains with α-1,6 linkages; isomaltose)  Free monomers and disaccharides are intact  Non-digestible starches and cellulose remain intact Monosaccharide absorption  Sucrose, maltose & lactose cannot diffuse through the phospholipid bilayer  They all require brush-border enzymes to hydrolyse into monomers  Glucose cannot diffuse through the phospholipid bilayer  Glucose requires a transporter (facilitated diffusion or active transport)  Galactose & fructose also cannot diffuse through the phospholipid bilayer  They both require transporters  Transport across Small intestine Enterocytes efflux influx Simple diffusion – crosses membrane Passive transport (facilitated diffusion) Active transport (requires energy; = specialised protein transporter or channel ATP)  down a concentration gradient  Against a concentration gradient - large nutrients e.g. sugars, amino acids - some small nutrients/ ions Enterocytes are specialised epithelial cells Absorbed nutrients go into blood capillaries [hepatic portal vein – goes directly to liver] or lymph vessels (most fat)  Enterocytes are specialised epithelial cells  (Transmembrane) Enzymes on the outside surface of the brush-border help in digestion:  Disaccharidases Maltase Sucrase-Isomaltase \ Lactase  Peptidases  (Transmembrane) Protein carriers carry specific compounds into the enterocytes Active transport of glucose outside/ gut lumen apical membrane An epithelial cell is polarized Inside enterocyte (it has an orientation) basal membrane outside/ blood vessel  Maltose Glucose Glucose Sucrose apical Lactose Galactose Glucose & Fructose Brush-Border disaccharidases: Lactase >> glucose and galactose Maltase>> glucose and glucose Sucrase (-isomaltase) >> glucose and fructose basal An Enterocyte  Na+ glucose apical LOW glucose Na+ HIGH sodium-dependent Brush-Border active glucose Transporter transporter basal An Enterocyte  Na+ glucose glucose Na+ secondary active transporter Na+ GRADIENT Sodium-Potassium Pump 3 Na 2K + + ATP primary ADP active transport uses ATP basal 3 Na+ 2 K+ N Glucose transport  Two main types of glucose transporters have been identified:  sodium–dependent glucose transporters (SGLTs) (secondary active transport – requires energy)  glucose transporters (GLUTs) (passive transport/ facilitated diffusion) Transport of glucose through an intestinal epithelial cell (enterocyte) Active transport of glucose by SGLT1 through apical border Passive transport of glucose by GLUT2 through basal border  Major characteristics of SGLT1 & 2 SGLT Location Function Type SGLT1 Apical membranes of small Absorption of glucose from intestinal content intestinal cells Straight cells (S3 segment) of Re-absorption of proximal tubule of nephron remaining glucose from urine filtrate Taken from Bays, H. (201 SGLT2 Proximal convoluted tubule of Re-absorption of bulk nephron (S1 and S2 segments) plasma glucose from glomerular filtrate Major characteristics of GLUT transporters GLUT type Location Primary Function GLUT1 All mammalian tissues Basal glucose uptake GLUT2 Small intestine, liver, kidney and Glucose, galactose and fructose transport pancreatic β-cells in the small intestine, liver and kidneys GLUT3 All mammalian tissues, major transporter Basal glucose uptake across blood-brain barrier GLUT4 Muscle and fat cells Major mediator of glucose removal from (insulin dependent) plasma GLUT5 Small intestine Fructose transport Summary transport of sugars in the intestine  Glucose and galactose use SGLT1, and fructose uses GLUT5 to move from the gut lumen into the enterocyte.  Glucose, galactose and fructose all use GLUT2 to exit the cell into the blood. Summary transport of sugars in the intestine  Fructose is absorbed independently by a passive transporter called GLUT5. Fructose absorption is limited by GLUT5 saturation (highly variable in population). Summary of key points so far: Many different types of carbohydrates enter our diet from varied sources. Only mono-saccharide sugars can be absorbed. Structure of the carbohydrate determines whether it can be digested in the small intestine (e.g. amylose vs cellulose). Summary of key points so far: Mono-saccharide sugars can be only be absorbed if there are transporters available Variation between individuals in some enzymes and some transporters (e.g. lactase and GLUT5) The gut microbiome can utilise virtually all the sugars from any form Nutritional Advances in Practice Part 4: Regulation of Blood Glucose & the Glycaemic Response R Key functions of carbohydrate in the body 1) Provide energy in the form of glucose (to produce ATP) 2) Reserve energy (e.g. glycogen) 3) Formation of cell organelles/ membranes (e.g. DNA, glycoproteins, glycolipids) Homeostasis Corrective Detection mechanism of change brings about a Increase return to norm from norm NOR NOR M M Decrease Negative Feedback from Corrective norm mechanism Detection of change brings about a return to norm  Overview – Endocrine System endocrine cell Hormones are chemical messengers – sent by endocrine glands in the blood to target cells/ tissues to produce a blood response target cell Overview – Endocrine System endocrine input cell -synthesis and release of hormone FEEDBACK blood target cell degradation of hormone -hormone activates response in target Hormone Receptors  “lock and key” fit  all cells have multiple receptors  each receptor is specific to a certain hormone and it is the hormone-receptor complex that initiates change within the cell  different targets can have identical receptors but, once bound to hormone, will have different effects specific to the target  pancreas – β-cells from increased blood Islets of Langerhans glucose after food endocrine input cell -synthesis and release of hormone FEEDBACK blood lower blood glucose - negative feedback responses in: -liver, muscle, pancreas & adipose target cell degradation of hormone -hormone activates response in target  What happens when blood glucose levels rise? Stimulus (elevated blood glucose) Insulin released from beta cells of Islets of Langerhans Stimulates glycogen formation, and glucose uptake (GLUT4) Decreases blood glucose concentration  What happens when blood glucose levels fall? Stimulus (decreased blood glucose) Glucagon released from alpha cells of Islets of Langerhans Stimulates glycogen breakdown to glucose and release into blood Increases blood glucose concentration Taken from textbook: Marieb and Hoehn (2018) Human Anatomy and Physiology. Chap 16, p.663.  Insulin is produced in response to feeding and increased blood glucose levels Roles of insulin: 1) to stimulate conversion of glucose to glycogen for storage in liver 2) to increase glucose transporters (GLUT4) in muscle cells in order to reduce blood glucose levels 3) to increase activity of lipoprotein lipase (particularly at adipose tissue) to increase uptake of free fatty acids 4) to inhibit glucagon synthesis and release in pancreas Glucose uptake in muscle cells 1 Insulin binds to the insulin Blood GLUCOSE 1 INSULIN receptor on the cell membrane INSULIN RECEPTOR 3 +2 3 Glucose transporters IRS-1 (GLUT4) are MAP-kinase 2 (insulin receptor translocated to the substrate 1) Response is cell membrane PI3K initiated within (phosphatidyl the cell inositol 3-kinase) GLUCOSE (GLUT4) RECEPTORS Glucose uptake in muscle cells Blood GLUCOSE 4 INSULIN Glucose is INSULIN RECEPTOR rapidly taken 4 into the muscle cell due to the + increase in IRS-1 GLUT4 MAP-kinase (insulin receptor transporters substrate 1) PI3K (phosphatidyl inositol 3-kinase) GLUCOSE (GLUT4) RECEPTORS Insulin resistance in muscle cells Blood GLUCOSE INSULIN Fatty acids INSULIN RECEPTOR Activation of 5 kinases inhibit the activation from the + IRS-1 5 - Kinase insulin receptor – MAP-kinase (insulin receptor even though insulin substrate 1) is bound to the receptor GLUCOSE (GLUT4) RECEPTORS Insulin resistance in muscle cells Blood GLUCOSE INSULIN Blood glucose Fatty acids INSULIN RECEPTOR remains HIGH + IRS-1 5 - Kinase MAP-kinase (insulin receptor substrate 1) GLUT4 are not translocated to the cell membrane GLUCOSE (GLUT4) RECEPTORS Diabetes thresholds Condition 2 h blood Fasting glucose HbA1C glucose Unit mmol/l(mg/dl) mmol/l(mg/dl) mmol/mol DCCT % Normal