Digestion & Absorption for Class 1

(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)

Potatoes, rice, wheat , bread, onions

Glycogen Meat, Liver

Sucrose Table sugar, desserts, sweets

Lactose Milk, Milk products

Dietary CarbohydratesFructose Fruits, Honey

Trehalose Mushrooms

Glucose Fruit, Honey, Grapes

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

Trisacchride of Gal-Glu-Fru

Stachyose Beans, soya beanscannot be digested by human gut

Tetrasacchride-Gal- Gal-Glu-Fr

Verbascose

Beans, soya beanscannot be digested by human gut

Pentasacchride-Gal- Gal- Gal-Glu-Fru

Starch• Major storage

carbohydrate in plants

• Amylose – long straight glucose chains (α 1-4) – 20 -30 % of starch

• Amylopectin – branched every 24-30 glc residues (α 1-6)- 70% of starch

• Provides 80% of dietary calories in humans

Glycogen

G

GG

G

G

GG

Ga 1-4 linkG

G

G

GG a 1-6 link

GG

G

GGG

• Storage carbohydrate in humans & animals

• Homopolysacchride of Long straight glucose chains

• Glucose residues linked by α 1- 4 glycosidic bond

• Branched every 4-8 glucose residues α 1-6 glycosidic linkage at branch points

• More branched than starch

• Less osmotic pressure & Easily mobilized


• 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

• 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 α-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 carbohydratesSalivary α-Amylase• Hydrolysis of starch (amylose &

amylopectin) & Glycogen• Products - Maltose, Isomaltose,

Maltotriose, (a trisacchride of glucose) ‘α Limit dextrin’ (branched oligosachrride)

• Endoglucosidase - acts only on the internal α 1,4 glycosidic bonds

• Does not act on α 1,6 bonds and α 1,4 bond at the non reducing end of a chain and α 1,4 bonds at the branch point

Digestion of carbohydrates

Salivary α-Amylase• α 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 carbohydratesPancreatic 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, ‘α 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 α-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– α 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


α Glucoamylase – an oligosaccharidase

• an exoglucosidase specific for 1,4 bonds between glucosyl residues from non-reducing end of a polysaccharide or α-limit dextrin, and hydrolyzes the bonds one after the other

• End product is glucose & isomaltose.

• It will digest α-limit dextrin down to glucose, & isomaltose

• that is subsequently hydrolyzed principally by the isomaltase activity in the sucrase–isomaltase complex


α Glucoamylase activity


• Sucrase–Isomaltase - 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


• Trehalse • Hydrolyses

trehalose – a disaccharide containing 2 glucose units in a 1,1 glycosidic linkage


• Lactase - - exists as β-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


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

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

Digestion of Carbohydrate

• Pancreatic Amylase – Highest activity in duodenum

• Sucrase-Isomaltase – jejunum

• α- Glucoamylase –progressively increase from jejunum to ileum

• Lactase / β -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


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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

TO CAPILLARIES

ABSORPTION OF MONOSACCHARIDES

Lumen ofintestine

INTESTINAL EPITHELIAL CELL

Fructose; also glucose,

Glucose Galactose Na+

2K+

3Na+

ATP

ADP + Pi

= facilitated diffusion

= Na+-dependent co-transport

= Na,K-ATPase

contraluminal membrane

GLUT-5

Brush border

SGLT-1

Fructose

GLUT-2

Na+

2K+

3Na+

Glucose

Galactose

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

Lactase & lactose intolerance• 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

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

http://www.amazon.com/dp/B000UCE446?tag=blogger400-20

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)

Sodium Chloride Glucose

KClSodium Citrate

DILIP MAHALANBIS, AN INIDAN

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. .

• 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

CELL MEMBRANE

GluT Structure

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 Tissue distribution Km Function

GluT 1 Brain, RBC, kidney, colon placenta, retina

Low Km, High affinityLow capacity transporters

Basal Uptake of glucoseReach 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)


Type Tissue distribution Km Function

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)

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 Function

GluT 4 skeletal muscle, heart muscle & Adipose tissue

High affinity, low Km,High capacity

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 5 luminal side of Intestinal epithelium, Spermatozoa

Low affinity, High Km, Low capacity

Also a fructose transporter


Type Tissue distribution Function

SGLT 1 Luminal side small Intestinal epithelium

Active uptake from small intestinal lumen into enterocyte against conc. Gradient

SGLT 2 Luminal side PCT epithelium

Active uptake of glucose from tubular lumen against a concentration gradient

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Digestion & Absorption for Class 1