(C.

H2O)n Hydrates of Carbon

Common Dietary Carbohydrates Monosaccharides

Common Dietary Carbohydrates - Disaccharides

Dietary carbohydrates Polysacchrides (complex carbohydrates)

Oligosaccharides -3 to 10 units Polysaccharides - more than 10 units Starch storage form of glucose in plants Glycogen-storage form of glucose in animals Dietary fiber Undigestible carbohydrates Soluble fibre & insoluble fibres cellulose, hemi-cellulose, lignin, pectin,

Dietary Carbohydrates
Starch (Amylose & Amylopectin) Glycogen Sucrose Potatoes, rice, wheat , bread, onions Meat, Liver Table sugar, desserts, sweets Milk, Milk products

Lactose

Dietary Carbohydrates Trehalose Mushrooms

Fructose Glucose Fruits, Honey Fruit, Honey, Grapes

Raffinose,

Stachyose

Verbascose

Leguminous seeds, beans, peas cabbage, whole grains cannot be digested by human gut Beans, soya beans cannot be digested by human gut Beans, soya beans cannot be digested by human gut

Trisacchride of Gal-Glu-Fru

TetrasacchrideGal- Gal-Glu-Fr PentasacchrideGal- Gal- GalGlu-Fru

Starch
Major storage carbohydrate in plants Amylose long straight glucose chains ( 1-4) 20 -30 % of starch Amylopectin branched every 24-30 glc residues ( 1-6)- 70% of starch Provides 80% of dietary calories in humans

Glycogen
Storage carbohydrate in humans & animals Homopolysacchride of Long straight glucose chains
G G G G G G G

Glucose residues linked by 1- 4 glycosidic bond

G G

G G G G G

a 1-6 link

a 1-4 link

G Branched every 4-8 glucose G residues 1-6 glycosidic linkage at branch points Less osmotic pressure & Easily mobilized More branched than starch

Dietary Carbohydrates
Daily dietary carbohydrates consumption is around 250 to 400 gm Constitute 50 to 70 % of our total caloric intake Complex carbohydrates - starch constitutes 50-60 % of this 200-250 gm of glucose is utilised daily by our body About 120 gm is utilised by brain & 30 gm by other tissues of CNS Only 50 to 100 gm by other tissues

Dietary Carbohydrates
Although all cells require glucose for metabolic functions, neither glucose nor other sugars are specifically required in the diet. Glucose can be synthesized from many amino acids found in dietary protein. Fructose, galactose, xylose, and all the other sugars required for metabolic processes in the human can be synthesized from glucose Recommended Dietary Allowance for humans (RDA) - 130 gm /day a minimum of 100 gm of carbohydrate is required daily in diet to prevent ketosis(breakdown of lipids)

Digestion of carbohydrates
dietary polysaccharides and disaccharides are converted to monosaccharides by GLYCOSIDASES, enzymes that hydrolyze the glycosidic bonds between the sugars. All glycosidic enzymes exhibit some specificity
for the sugar the glycosidic bond number of saccharide units in the chain

Digestion of carbohydrates
Digestion begins in mouth

Hydration of polysaccharides is essential for the action of -amylase as digestive enzymes are hydrolases
Mastication & Chewing essential for homogenization & hydration of dietary polysaccharides Efficiency of salivary digestion depends on the extent of chewing

Digestion of carbohydrates
Salivary -Amylase Hydrolysis of starch (amylose & amylopectin) & Glycogen Products - Maltose, Isomaltose, Maltotriose, (a trisacchride of glucose) Limit dextrin (branched oligosachrride) Endoglucosidase - acts only on the internal 1,4 glycosidic bonds Does not act on 1,6 bonds and 1,4 bond at the non reducing end of a chain and 1,4 bonds at the branch point

Digestion of carbohydrates
Salivary -Amylase Limit dextrins an oligosaccharide formed as a result of limited action of amylase (beyond which it cannot act) Usually has 4 to 9 glucosyl units (average 8) with one or more 1,6 branches. Requires chloride ions for its activity

Digestion of carbohydrates
Pancreatic Amylase Major digestion of polysacchrides Similar to salivary amylase in action. Salivary & Pancreatic amylase - true isoenzymes allozymes (protein products of different genes (in different /same chromosomes) Products are same - Maltose, Isomaltose, Maltotriose, Limit Dextrin failure of exocrine pancreatic secretion will therefore affect the digestion of carbohydrates - as in cystic fibrosis, chronic pancreatic disease

Action of Salivary & Pancreatic -amylase

Intestinal digestion of carbohydrates

The dietary disaccharides lactose and sucrose & products of starch digestion, are converted to monosaccharides by intestinal disacchridases Attached to the membrane in the brush-border (villi) of intestinal absorptive cells : not secreted into lumen Lactase Sucrase-Isomaltase complex Glucoamylase - oligosaccharidase Lactase- glucosylceramidase Trehalse

 All intestinal disacchridases are inducible enzymes The greater the amount of a disaccharide found in the diet or produced by digestion, the greater is the amount of a specific disaccharidase produced by the enterocyte Exception - lactase is not inducible - constant secretion

Intestinal digestion of carbohydrates

 Glucoamylase an oligosaccharidase an exoglucosidase specific for 1,4 bonds between glucosyl residues from non-reducing end of a polysaccharide or -limit dextrin, and hydrolyzes the bonds one after the other End product is glucose & isomaltose. It will digest -limit dextrin down to glucose, & isomaltose that is subsequently hydrolyzed principally by the isomaltase activity in the sucraseisomaltase complex

Intestinal digestion of carbohydrates

Intestinal digestion of carbohydrates

Glucoamylase activity

Intestinal digestion of carbohydrates

SucraseIsomaltase - a single polypeptide chain 2 separate subunits that remain attached to each other Each subunit has a catalytic site for sucrose & iso maltose & maltose exhibits sucarse, maltase & isomaltase activity

Intestinal digestion of carbohydrates Trehalse Hydrolyses trehalose a disaccharide containing 2 glucose units in a 1,1 glycosidic linkage

Intestinal digestion of carbohydrates

Lactase - - exists as -Glycosidase complex (lactase-glucosylceramidase) attached to the brush border of intestinal villi a single polypeptide chain with 2 separate subunits that remain attached to each other Each subunit has a catalytic for lactose & glycolipids

Intestinal digestion of carbohydrates

The lactase catalytic site hydrolyzes the -1,4 glycosidic bond connecting glucose and galactose in lactose

The other catalytic site hydrolyses - bond between glucose or galactose and ceramide in glycolipids

Digestion of Carbohydrate
Pancreatic Amylase Highest activity in duodenum Sucrase-Isomaltase jejunum - Glucoamylase progressively increase from jejunum to ileum Lactase / -glycosidase Jejunum

Fermentation of dietary carbohydrates by colonic bacteria

Not all dietary starch ingested as part of foods is completely digested in the small intestine Starches - high in amylose, or less well hydrated are resistant to digestion and enter the colon. Dietary fibers (cellulose, hemicellulose, pectins, lignins) cannot be digested because glycosidases cannot hydrolyse their glycosidic bonds .

Fermentation of dietary carbohydrates by colonic bacteria

colonic bacteria rapidly metabolize these saccharides, forming gases H2 , CO2,CH4 , short-chain fatty acids & lactate The short-chain fatty acids are absorbed by the colonic mucosal cells and provide a source of energy for these cells. These gases are released through the colon resulting in abdominal distension, flatulence, or in the breath. Incomplete products of digestion in the intestines increase the retention of water in the colon, resulting in diarrhea.

Undigestible dietary carbohydrates

Glucose absorption

Digestion of Carbohydrates

Dietary Carbohydrates
? ?

Carbohydrate absorption
Only monosaccharides can be absorbed from intestine Only D-isomers of sugars are absorbed and not L-sugars Absorption takes place in duodenum, jejunum & ileum

Rate of absorption greatest for galactose; least for fructose

Galactose > Glucose > Fructose Different sugars have different mechanisms for absorption

Glucose absorption
Glucose is an uncharged polar molecule hence cannot diffuse by simple diffusion through lipid bilayer of membrane inspite of conc.gradient Passive Transport (Facilitated Diffusion) with the help of Transport / Carrier Proteins down concentration gradient called GluT (Glucose Transporters) Secondary Active Transport against concentration gradient - energy dependent utilising ATP

Glucose absorption

Glucose absorption
Glucose & Galactose are absorbed against their concentration gradient along with sodium (Co transport Symport) The sodium ions flow down their concentration gradient while the glucose molecules are pumped up against their conc gradient An energy requiring process Secondary Active transport Energy derived indirectly from hydrolysis of ATP by Na+K + ATPase. Hence called Secondary Active Transport

SGLT 1

GLUT 2

Glucose Absorption
Sodium ions pumped back out of the cell by the Na+/K+ ATPase in order to maintain their concentration gradient & intracellular electrical neutrality

SGLT 1 Sodium Glucose Transporter 1

2 different sites for binding 1 for Na and another for glucose (SGLT 2 is present in the PCT of kidney for reabsorption of glucose from Glomerular filtrate)

Glucose absorption
From inside cell into capillary blood of portal circulation by GluT 2 by facilitated transport down the gradient

PASSIVE TRANSPORT NOT REQUIRING ENERGY

GLuT 2 is located on the basal membrane of endothelial cells on anti luminal side enterocyte

GLUT 2

Glucose Fructose; also glucose, INTESTINAL EPITHELIAL CELL

Na+

Galactose

Lumen of intestine

GLUT-5

SGLT-1

Brush border
Fructose

Glucose
Galactose

Na+

3Na+ 2K+

ATP ADP + Pi

contraluminal membrane

GLUT-2

TO CAPILLARIES = facilitated diffusion

3Na+ 2K+

= Na,K-ATPase

+ = Na -dependent co -transport

ABSORPTION OF MONOSACCHARIDES

Absorption of Fructose
Passive Facilitated Transport Down its conc. gradient with the help of GluT 5 (also for Glucose & galactose) From inside cell into capillary blood of portal circulation by GluT 2 by facilitated transport down the gradient located on the basal membrane of endothelial cells on anti luminal side enterocyte fructose is absorbed at a much more rapid rate when it is ingested as sucrose than when it is ingested as a monosaccharide

Abnormal degradation of disaccharides Lactose Intolerance

As disacchrides are not absorbed and only monosaccharides are absorbed, any defect in a specific disaccharidase activity of the intestinal mucosa causes the passage of undigested carbohydrate into the large intestine. As a consequence of the presence of this osmotically active material, water is drawn from the mucosa into the large intestine, causing osmotic diarrhea. Also undigested disacchride undergoes fermentation by the bacteria to two- and three-carbon compounds (which are also osmotically active) & large volumes of CO2 and H2 gas, causing abdominal cramps, pain, diarrhea, and flatulence, bloating

 Lactose intolerance is a condition of abdominal pain, cramps, nausea, and flatulence, diarrhoea after the ingestion of foods containing lactose, mainly milk & dairy products Primary lactose intolerance due to low lactase activity inherited Secondary lactose intolerance due to injury to intestinal villi due to kwashiorkar, AGE, colitis, non tropical sprue, chronic alcoholism all disacchridases are affected but others sucrase, maltase, isomaltase, and glucoamylase activities are usually present at such excessive levels that no pathological effects occur Lactase is the first to be affected and last to recover

Lactase & lactose intolerance

Normal lactose digestion

Lactose digestion in intolerance

Treatment of lactose intolerance

Reduction or avoidance of lactose containing Foods depending on the severity of the deficiency of intestinal lactase. Cheeses are low in lactose for patients with mild to moderate lactase deficiency. Yogurt contain bacteria that release free lactases when the bacteria are lysed by gastric acid and proteolytic enzymes. Commercially available milk products that have been hydrolyzed with a lactase enzyme provide a 70% reduction in total lactose content, in mildly affected patients. Soy protein Milk free from lactose Tablets and capsules containing lactase

Lactose intolerance

Special lactose free milk substitutes for intolerance Lactase

Glucose transport - SGLT 1 & Clinical relevance

A practical application of this is taken advantage during the treatment of Acute Gastroenteritis esp. children due to rota virus diarrhoea & in adults & children due to cholera

the fact that the Na+- dependent transporters for glucose and amino acids are not affected by the cholera exotoxin is taken advantage of..

Glucose transport SGLT 1 & Oral Rehydration Salt (ORS)

DILIP MAHALANBIS, AN INIDAN

Sodium Chloride Glucose KCl Sodium Citrate

Glucose transport - SGLT 1 & Clinical relevance

Oral Rehydration Solution (ORS) APPROVED by
WHO in 1978 and is given for rehydration during AGE, & has both glucose and Na ( in addition to potassium and bicarbonate/citrate)

As a result, co administration of glucose and Na+ by mouth results in the uptake of glucose & Na+, accompanied by chloride and water, thereby partially correcting the ion deficits and fluid loss Sodium absorption in the gut is facilitated when some glucose is present in the intestinal lumen. .

GluT Structure
CELL MEMBRANE

Carrier proteins transport glucose across cell membranes called GluT Glucose Transporters 5 glucose transporters ( GLUT 1, 2, 3, 4, 5) in humans with different kinetic characteristics Transmembrane proteins Differ in Affinity, Substrate Specificity, Distribution, Inducibility Single polypeptide with 12 transmembrane spanning domains

Why Glucose Transporters required?

Glucose cannot diffuse across cell membranes although its concentration is high outside the cell compared to inside This is because glucose is uncharged & polar and hence cannot diffuse through the lipid bilayer of membrane even though the conc. gradient is favorable . Also following transport across the cell membrane phosphorylation by GK /HK inside the cell is required to prevent it from leaving the cell

Types of Glucose Transporters

Type GluT 1 Tissue distribution Brain, RBC, kidney, colon placenta, retina Km Low Km, High affinity Low capacity transporters Function Basal Uptake of glucose Reach VMax even at normal glucose conc.

GluT 2 Liver, pancreatic b cell, Serosal surface of intestine, Luminal surface of PCT in kidney

High Km, low affinity, High capacity transporters

Glucose sensor in pancreas Reach Vmax only at high conc (following meal)

Types of Glucose Transporters

Type Tissue distribution Km High Km, low affinity, High capacity transporter s Function Glucose sensor in pancreas Reach Vmax only at high conc (following meal) GluT 2 Liver, pancreatic b cell, Serosal surface of intestine, Luminal surface of PCT in kidney

GluT 3 Brain Kidney, Placenta Low Km High affinity

Basal Uptake of glucose - Reach VMax even at normal glucose conc

Types of Glucose Transporters

Type Tissue distribution Km High affinity, low Km, High capacity Function Insulin-sensitive transporter. In the presence insulin number of GLUT 4 transporters increase on cell surface increase recruitment of GLUT 4 from cytoplasmic vesicles

GluT 4 skeletal muscle, heart muscle & Adipose tissue

GluT 5 luminal side of Intestinal epithelium, Spermatozoa

Low Also a fructose affinity, transporter High Km, Low capacity

Types of Glucose Transporters

Type Tissue distribution Function

SGLT 1

Luminal side small Intestinal epithelium

SGLT 2

Luminal side PCT epithelium

Active uptake from small intestinal lumen into enterocyte against conc. Gradient Active uptake of glucose from tubular lumen against a concentration gradient