DIGESTION AND ABSORPTION OF CARBOHYDRATES (GLYCANS)

4 Major Classes of Carbohydrates• Monosaccharide – simple sugars

– Glucose– Fructose

• Disaccharide – 2 monosaccharides – Sucrose– Lactose

• Oligosaccharide – few monosaccharides (cell membrane)

• Polysaccharide – polymer consisting of disaccharides and monosaccharides

– Starch– Cellulose

Polysaccharides

Digestion of Carbohydrates1. Mouth

– Salivary α-Amylase (Ptyalin)• Contained in the salivary

secretions• Catalyzes the α-1,4 glycosidic

bonds (linear)• PRODUCTS:

– α-1,4 Maltose – disaccharide

– α-1,4 Maltotriose – trisaccharide

– α-limit Dextrin – branched oligsoccharides (α-1,4 and α-1,6)

2. Stomach– No digestion of carbohydrates– Gastric Acid (HCl) – inactivates salivary

α-amylase 3. Small Intestine

– Pancreatic α-amylase (duodenum)• Contained in the pancreatic

juice• Further catalyzes the α-1,4

glycosidic bonds• PRODUCTS:

– Maltose– Maltotriose

– α-1,4 Maltooligosaccharides

– α-limit Dextrin– Brush Border Membrane (epitehlium of

duodenum and jejunum)• Oligosaccharidases

– Lactase – Lactose → Glucose & Galactose

– Sucrase – Sucrose → Fructose & Glucose

– Isomaltase (α-Dextrinase) – debranches α-limit Dextrin

– Glucoamylase – Maltooligosaccharides → Glucose units

• PRODUCT: Glucose units

Summary of Digestion of Carbohydrates

Absorption of Carbohydrates

Plant Starch

Amylose

Cellulose

β-1,4

Transport System

GLUT5 Transport

Sodium-Glucose Transport• Active entry of Glucose and Galactose into the

intestinal epithelial cells – stimulated by the presence of Sodium in the lumen

• Membrane Protein– Transports Glucose, Galactose, and

Sodium into the cell– 2 binding sites:

• Sodium-binding site• Sugar-binding site

• Sodium– Pass through the large electrochemical

potential gradient (made by sodium, potassium-ATPase molecule in the basal and lateral plasma membranes)

– Concentration and electrical forces – drives sodium into the cell

– Transported by PRIMARY ACTIVE TRANSPORT – by the sodium-potassium pump

• Glucose and Galactose – Goes against a concentration gradient

for the sugar– Energy released by the flow of sodium

to the electrochemical potential – drives/forces glucose and galactose into the cell

– Transported by SECONDARY ACTIVE TRANSPORT – since it depends on the electrochemical gradient of sodium

• Exit– Via facilitated diffusion (or to some

extent, simple diffusion)– Glucose and Galactose leave the

intestinal epithelial cell at the basal and lateral plasma membrane

– Diffuses into the mucosal capillaries GLUT5 Transport

• Transports fructose across the enterocyte (intestinal epithelial cell)

• Via facilitated diffusion – because of high concentration of fructose

Extent of Absorption of Carbohydrates• 6%-10% of 20/60 grams of starch escapes

absorption in the small intestine – failure to absorb carbohydrate completely

• Passed on the colon– Serves as an excellent carbon source for

colonic bacteria Carbohydrate Malabsorption Syndromes

• Lactose Malabsorption Syndrome– Deficiency of Lactase in the brush

border

– Goes to colon and enhances colonic bacteria’s motility

– Symptoms:• Lactose intolerant• Intestinal distention• Borborygmi – gurgling noises

made by the intestine as It mixes gas and liquid

• diarrhea • Congenital Lactose Intolerance

– Infants who lack lactase have diarrhea when fed breast milk or milk formula containing lactose

– May result to dehydration and electrolyte imbalance

– Fed formula with sucrose or sucrose instead of lactose

• Sucrase-Isomaltase Deficiency– An autosomal recessive, inherited

disorder– Intolerance to ingest sucrose

• Glucose-Galactose Malabsorption Sydrome – Hereditary– Defect in the brush border sodium-

glucose transport– Ingestion of glucose, galactose, or

starch leads to flatulence and severe diarrhea

Digestion and Absorption of Protein

Digestion in the stomach Chief cells secrete inactive protein pepsinogen,

which is converted by hydrogen ions to the active enzyme, pepsin.

Pepsin reduces only about 15% of dietary protein to amino acids and small peptides

Digestion in the duodenum and small intestine Proteases

o secreted by pancreaso plays a major role in protein digestiono Conducts proteolysiso Important proteases:

Trypsin , Chymotrypsin, Carboxypeptidase A, and, Elastase

Digestion in the duodenum and small intestine Enteropeptidase (enterokinase)

o Secreted by mucosa of duodenum and jejunum

o Trypsinogen → Trypsin Trypsin

o Acts autocatalytically to activate trypsinogen

o Converts other proenzymes to the active enzymes

About 50% of ingested protein is digested and absorbed in the duodenum

Brush borders of duodenum and small intestine contains peptidases

These peptidases are integral membrane proteins whose active sites face the intestinal lumen

Proximal jejunum contains the highest amounts of brush border enzymes

• These enzymes reduce the peptides produced by pancreatic proteases to oligopeptidases and amino acids.

Brush border peptidases: Aminopeptidases – cleave single amino

acids from the N terminals of peptides Dipeptidases – cleave dipeptides to

amino acids Dipeptidyl aminopeptidases – cleave a

dipeptide from the N-terminal end of a peptide.

Small peptides and amino acids Small peptides and amino acids – principal products

of protein digestion by pancreatic proteases and brush border peptidases

Small peptides (dipeptides, tripeptides, and tetrapeptides)

• Produced in concentrations about three to four times higher than those of single amino acids

Transported across the brush border plasma membrane into intestinal epithelial cells

Small peptides then hydrolized by peptidases in the cytosol of the epithelial cells

Absorption of intact proteins and large peptides

Not absorbed by humans to an extent that is nutritionally significant

Small amounts of luminal proteins are taken up by the Microfold cells (M cells) of the mucosal immune system (peyer’s patches)

Absorption of small peptides Rate of transport of these small peptides usually

exceeds the rate of transport of individual amino acids

In experiments, glycine was absorbed by the human jejunum less rapidly as a single aminno acid than it was as diglycine or triglycine

Single membrane transport system Responsible for the absorption of small

peptides ↑ affinity for dipeptides and tripeptides,

very ↓ affinity for peptides of our or more amino acid residues.

Stereospecific – prefers L-amino acids ↑ affinity or bulky side chains

Secondary Active Transport Transport of dipeptides and tripeptides

is powered by the electrochemical potential difference of H+ across the membrane

Jejunum more active in uptake of di- & tripeptides

Most of small peptides are cleaved to single amino acid in the cell and absorbed into blood as single amino acid

Absorption of Amino Acid Ileum is more active in the uptake of single amino

acidBrush border membrane

Basolateral membrane

Transport Via specific amino acid transport systems (into epith. cells)

Via different set of transporters (out of epith. Cells)

Transporters

Mostly unique to epithelial cells

Occurs in many epithelial cells

Brush border & basolateral membrane• some transporters depends on the Na+

gradient, some transport systems are independent of Na+

• Simple diffusion as significant pathway• The more hydrophobic the amino

acid and the larger its concentration

gradient across membrane, the greater importance of diffusion

Brush border membraneo Na+ dependent

• amino acid uptake: secondary active transport

o Na+ independent• amino acid uptake: Facilitated transport

Basolateral membraneo Na+ dependent - Mediate active uptake of

amino acids. Provide amino acid for protein synthesis in the epithelial cells during indigestive periods.

o Na+ independent - Responsible for efflux of amino acids into the blood

Defects of Amino Acid Absorption Hartnup’s disease - Rare hereditary disorder

– Defective renal and intestinal transport of neutral amino acids

– Caused by defects of B system of the small intestine and the proximal renal tubule

Cystinuria - Presence of cystine in urine

– Caused by a defect in either B0,+ or b0,+

transporters in brush border membrane in the epithelial Cells of small intestine and renal proximal tubule

Prolinuria - Defective renal and intestinal reabsorption of proline

– Defect in IMINO system in the epithelial brush border plasma membrane of the small intestine and renal proximal tubule

– Hartnup’s disease, cystunuria, and Prolinuria do not result into malnutririon, because the epithelial cells are still capable of absorbing dipeptides and tripeptides

INTESTINAL ABSORPTION OF WATER AND SALTS

ABSORPTION OF WATER

• Water absorption in the body generally takes place in the small intestines about 90% and 10% occurs at the large intestine

• Movement of absorption is from blood to lumen and from lumen to blood

• About 2L of water is ingested daily about 7L are present in daily gastrointestinal secretions and about 100mL is lost daily during defecation

• In the duodenum, little water absorption occurs because water is added to chyme to bring about its isotonicity. Also, the duodenum is very permeable to water.

• The jejunum is more active than the ileum in water absorption

• Little absorption happens in the large intestines but it can absorb water against high osmotic pressure than the small intestine

ABSORPTION OF Na⁺

• Na⁺ is absorbed throughout the entire length of the intestine

• Movement of absorption is from blood to lumen and lumen to blood

• From the jejunum, the absorption of Na⁺ is greater then lessen as is reaches the colo

• It is greatest in the jejunum because if the presence of glucose, galactose and neutral amino acids

• Na⁺ enhances absorption of sugars (glucose and galactose) and neutral amino acids vice versa

ROUTES OF INTESTINAL WATER AND SALT ABSORPTION

• TIGHT JUNCTIONS- the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid

• Transcellular transport- port involves the transportation of solutes by a cell through a cell.

• Paracellular Transport - refers to the transfer of substances between cells of an epithelium

• Villous Cells- projections found at tips of special epithelial cells which helps in absorption

• Crypt Cells- are found in less differentiated cells which produces net secretion of water and ions

MECHANISM OF WATER ABSORPTION

• It depends on the absorption of sodium and chloride ions

• In the small intestine, absorption of water occurs in the absence of osmotic pressure between the luminal contents and intestinal capillaries

• In the colon. Water absorption occurs against an osmotic pressure gradient. It is known as standing gradient osmosis which is when the lateral intracellular spaces are large and swollen. When fluid transport is blocked, intercellular spaces almost disappear

• Absorption of sugars and amino acids allows more water to be absorbed

PHYSIOLOGICAL REGULATION OF SALT AND WATER ABSORPTION

• ENDOCRINE CONTROL OF ABSORPTION AND SECRETION

– This is when hormones help in the absorption of water and salt

– Mineralcorticoids, glucocorticoids,catecholamines,somatostatin, enkephalins,aldosterone, opoids and ephinerphrine are hormones which help regulate absorption of salt and water

• NEURAL REGULATION OF ABSORPTION AND SECRETION

– ENTERIC NERVOUS SYSTEM

o Epithelial cells are innervated by the secretomotor neurons which stimulates net secretion.

– PARASYMPATHETIC NERVOUS SYSTEM

o The enteric nervous system is innervated by the parasympathetic fibers. The parasympathetic nervous system help in diminishing absorptive fluxes and enhance secretions

– SYMPATHETIC NERVOUS SYSTEM

o Stimulation of sympathetic fibers stimulate net absorption.

o It is related to the enteric nervous system in a way that the sympathetic fibers stimulate the enteric nerve fibers

• REGULATION OF ABSORPTION AND SECRETION BY THE GASTROINTESTINAL IMMUNE SYSTEM

– There are various mediators which enhance net secretion of water and electrolytes

– Mediators include histamine, serotonin, prostaglandin, thromboxanes, leukotrienes, platelet-activating factor,adenosine, reactive oxygen species, nitric acids and endothelin

– These mediator works in two ways

– Directly affect intestinal epithelial cells and either stimulate or inhibit absorption

o Act on enteric neurons to increase activities in secretomotor circuits

PATHOPHYSIOLOGICAL ATERATIONS OF SALT AND WATER ABSORPTION

• DEFICIENCY OF A NORMAL ION TRANSPORT SYSTEM

– Congenital chloride diarrhea

The chloride and bicarbonate exchange transport system in the brush plasma border of the ileum and colon is missing or deficient

It impairs the chloride absorption which leads to diarrhea with stools having a high chloride concentration

• ABNORMAL ABSORPTION OF A NUTRIENT

– Carbohydrate malabsorption syndromes wherein sugar is retained in the lumen of the small intestine increases the osmotic pressure in the lumen.

– As a result, water is also retained and chyme increases in volume which is then passed on to the colon. Increased chyme content in the colon impairs its ability to reabsorb electrolytes leading to diarrhea

• HYPERMOTILITY OF THE INTESTINE

– Its when the peristaltic movement of the intestine is great thus it cannot absorb the maximum amount of nutrients from the ingested food

• ENHANCED SECRETION OF WATER AND ELECTROLYTES

– It is when the intestines secrete too much water that the intestinal absorption cannot cope up.

ABSORPTION OF CALCIUM

CALCIUM IONS-Absorbed by all segments of the intestine.-Forms insoluble salts with many anions present

in food (phytate, phosphate, oxalate)These salts are soluble at low pH.

INTESTINAL ABSORPTION OF CALCIUM

Ability of intestine to absorb Ca2+ is regulated (lowCa diet = increase ability to absorb)(highCa diet = less to absorb)

Stimulated by Vitamin D

Parathyroid hormone- stimulates intestinal absorption of Calcium

HOW??*it promotes the release of the active form of

Vitamin D from the kidney.

Cellular Mechanism of Calcium Absorption

1. Ca2+ crosses the brush border plasma membrane via Ca2+ channels2. Calbindin binds to Ca+

WHAT IS CALBINDIN??-it’s a protein-also known as intestinal calcium binding proteins (CaBP).-allow large amounts of Ca2+ to traverse the cytosol-prevents concentrations of free Ca2+ ions to form insoluble salts with intracellular anions.

2 forms of Calbindin*Calbindin D9k-binds two Ca2+ ions*Calbindin D28k-binds 4 Ca2+ ions

3. Ca2+ is extruded across the basolateral membrane by Ca2+-ATPase and Na+ - Ca+ exchange mechanism.

What is Ca2+-ATPase and Na+ - Ca+??Ca2+ - ATPase

-Primary active transport -It splits ATP and uses the energy to transport

Ca-use when intracellular concentrations are low

Na+ - Ca2+ exchanger-Uses energy of the Na+ gradient to extrude

Ca2+ by secondary active transport-use when intracellular concentrations are high

ACTIONS OF VITAMIN D

Vitamin D- essential for normal levels of calcium absorption.*it stimulates each phase of absorption:

-passage across the brush border membrane.-traversal of the cytosol.-active extrusion across the basolateral

membrane.- By binding to nuclear receptors stimulating the synthesis of messenger RNA -Stimulating synthesis of Calbindin-D9k and Calbindin-D28K-Increasing the level of brush border associated Calbindin.-Increasing the level of the basolateral Ca2+-ATPASE

Vitamin D deficiencyRICKETS

-a condition where in the rate of absorption of Ca2+ is very low, causing low amount of Ca2+ available for bone growth.

In children with rickets, bone growth is abnormal. WHY?

There is a failure to deposit normal amounts of calcium salts in the bone matrix, bones are softer and more flexible than normal. These changes contribute to “bow- legged” appearance of children with rickets.

MALABSORPTION OF CALCIUMMay occur to those who have bowel disease

and disorder such as*Gluten enteropathy*Tropical sprue

-diminishes the surface area of the brush border.

ABSORPTION OF IRON

Iron absorption is limited..WHY??

*it forms insoluble salts with anions, such as hydroxide, phosphate, and bicarbonate that are present in intestinal secretions.

*it forms insoluble complexes with other substances commonly present in food such as phytate, tannins, and fiber of cereal grains.

->Insoluble complexes are more soluble to low pH. Therefore hydrochloric acid (HCl) enhances iron absorption.

(*so if someone has a deficiency in acid secretion iron absorption would be low)

What promotes iron absorption?ASCORBATE-Ascorbate forms a soluble complex with iron, preventing iron from forming insoluble complexes.

-reduces Fe3+ and Fe2+.(Fe2+- absorbed much better that Fe3+ because

its tendency to form insoluble complexes is much lesser than the Fe3+)

HEME IRON-Well absorbed.-Release by proteolytic enzymes from proteins

in the intestinal lumen.

Iron- is absorbed by villus enterocytes in the

proximal duodenum-Efficient absorption requires an acidic

environment, and antacids.

Cellular Mechanism of Iron Absorption

1. Ferric iron (Fe+++) in the duodenal lumen is reduced to its ferous form through the action of brush border ferrireductase.

2.2. Iron is co-transported with a proton into the enterocyte via the divalent metal transporter (DMT-1).

*when inside may follow 2 major pathways which depends on a complex programming of cell.

3. Following of pathways..

*Iron abundance states:-iron within the enterocyte is

trapped by incorporation into ferritin and hence, not transported into blood.

*Iron limiting states:- iron is exported out of the

enterocyte via a transporter (ferroportin). It then binds

to the iron-carrier transferrin for transport throughout the body.

Regulation of Iron Absorption -Iron absorption is regulated in accordance with

the body’s need for iron. Example:In chronic iron deficiency or after hemorrhage,

duodenum and jejunum increase their capacity to absorb iron.

Iron overload

-Absorption of more iron than needed.-Can result from chronic ingestion of large

amounts of absorbable iron.

*(common in African tribes that consume brewed beer with high iron content)

Idiopathic hemochromatosis-genetic disorder-excessive amount of iron is absorbed

from the diet that is normal in iron content.-is some cases there are increased

levels of the ion transport proteins DCT1 and IREG1.

Absorption of MagnesiumAbsorbed in the entire length of intestine but

the largest Magnesium absorption takes place in the ileum.

Absorption of Phosphate

Jejunum is responsible for the largest How is it absorb??

*phosphate crosses the brush border plasma membrane by Na+-powered secondary active transport. Then it leaves the cell by moving down to its electrochemical potential gradient across a basolateral membrane by means of facilitated transport.

Absorption of Copper

When dietary copper is low the ingested copper that is absorbed increases.

Individuals who fail to secrete sufficient amounts of copper in the bile, the body’s copper pool grows and cooper accumulates in certain tissues.

Digestion and absorption of lipids

The primary lipids of a normal diet are triglycerides. The diet contains smaller amount of sterol, esters, and phospholipids. Because lipids are slightly soluble in water, each stage of their processing poses special problem to the gastrointestinal tract.

The digestion product of lipids from small molecular aggregates known as micelles with the bile acids.

The digestion and absorption of lipids are more complex than for any other class of nutrients and are more frequently subject to malfunction.

Digestion of lipids in stomach

Significant hydrolysis of triglycerides occurs in stomach.

The enzymes are responsible for lipid hydrolysis in stomach are known as preduodenal lipasses,the enzymes operate most effectively at acids PHs. in rates, principally preduodenal lipase is lingual lipase, which is produced by glands under the circuvallate papillae of the tongue.

Digestion of lipids in the duodenum and jejunum

Pancreatic lipolytic enzymes. Pancreatic juice contains the major lipolytic

enzyme responsible for digestion of lipids. The most important digestive enzyme are

glycerol ester hydrolase ,colipase ,cholesterol ester hydrolase and phospholipase A,

The arrival of lipids in the duodenum causes secretion of bile and fat is emulsified by bile salt micelles.

Pancreatic lipase hydrolyzes triglycerides to free fatty acids and monoglycerides.

Phosphate A breaks down phospholipids into fatty acids and lysolecithin.

Then free faty acids, monoglycerides, and lysolecithin leaves micelles and enter the epithelial cells then they are resynthesized into triglycerides and phospholipids.

These combine to form chylomicrons. Then when the combine into the blood, they become apolipoprotein, which allow them to bind to receptors on capillaries in muscle and fat.

Cytosilic lipid transport protein

Handling of lipids inside the intestinal epithelial Proteins bind cholesterol and other sterols. Two classes of fatty acid-binding proteins exist in

the cytosol of epithelial cells of upper intestine I-FABP & L-FABP

Two isoforms of sterol carrier protein SCP-1 & SCP-2

Resynthesis of lipids in the smooth endoplasmic reticulum

The products of lipid digestion are carried by the binding proteins to the smooth endoplasmic reticulum

The intestinal epithelial cells are also capable of some synthesis of new lipids.

Absorption of bile acids Bile is a complex fluid containing water,

electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine

These are absorbed largely in the terminal part of the ileum.

Malabsorption of lipids Malabsorption is a clinical term that

encompasses defects occurring during the digestion and absorption of food nutrients by and infections of the gastrointestinal tract.

Among the general causes of lipid Malabsorption are bile deficiency, pancreatic insufficiency, and the intestinal mucosal atrophy that occurs in some disease states.