Carbohydrate Digestion and Absorption
Gregg Kobak, MD Christine Waasdorp Hurtado, MD, MSCS, FAAP
University of Colorado School of Medicine Children’s Hospital Colorado
Expert Reviewers: Jeremiah Levine, MD Richard Grand, MD NASPGHAN Physiology Education Series
Series Editors: Christine Waasdorp Hurtado, MD, MSCS, FAAP [email protected] Daniel Kamin, MD [email protected] Overview
• Carbohydrates are composed of carbon and water
• Composition = Cn(H2O)n.
• Carbohydrates are the major exogenous source of glucose • 40-60% of calories in the diet • Higher in protein scarce diet • Provide 4 calories per gram • No single carbohydrate is essential Carbohydrate Overview • Monosaccharides – Glucose – Galactose – Fructose • Disaccharides – Sucrose – Lactose – Maltose • Complex Carbohydrates – Starch • Amylose • Amylopectin – Dietary Fiber – Glycogen
Image from - E. Generalic. http://glossary.periodni.com/glossary.php?en=carbohydrate Simple Carbohydrates • Monosaccharides - – Basic unit of Carbohydrates – Most are 6 carbon hexoses • Ribose is 5 – Different molecular arrangements result in varying sweetness • Common Monosaccharides – Glucose – Fructose – Galactose – Xylose – Ribose
Image from: E. Generalic, http://glossary.periodni.com/glossary.php?en=monosaccharide Disaccharides - Pairs of monosaccharides • Joined by condensation • Separated by hydrolysis • Lactose – Glucose-Galactose – Found in nature primarily in mammalian milk • Maltose – Glucose-Glucose – Product of starch digestion • Sucrose – Glucose-Fructose – Table Sugar
Image from: E. Generalic, http://glossary.periodni.com/glossary.php?en=monosaccharide Complex carbohydrates
• Polysaccharides – Starch – Dietary fiber – Glycogen Starch
• Provides a large portion of dietary calories in humans worldwide • Major carbohydrate for energy storage • Plant source • Amylopectin – – branched polymers of glucose (a1,6) • Amylose – – simple straight chain glucose polymers (a1,4) – 25% of starch
Image from: E. Generalic, http://glossary.periodni.com/glossary.php?en=monosaccharide Fiber
• Found in most plant derived food • Cellulose • Pectin • Lignins – Structural parts of plants – Polymers are not digested by luminal hydrolases – Provides bulk to stool – Broken down in colon by bacterial hydrolase • Generate Short Chain Fatty Acids (SCFA) = energy for colonocytes
Image from: E. Generalic, http://glossary.periodni.com/glossary.php?en=monosaccharide Glycogen • Major storage carbohydrate in animals • Long straight glucose polymers (a1,4) • Branched glucose polymers (a1,6) • More branched than starch • Not found in plants • Not an important dietary source of carbohydrate
Image from: E. Generalic, http://glossary.periodni.com/glossary.php?en=monosaccharide Carbohydrate Overview
• Carbohydrates are hydrophilic • Series of reactions are required to digest – Polymers are too large for transport – Specific hydrolases for digestion – Most are broken down to monomers for absorption • Fiber is not broken down to monomer – Specific receptors for absorption Digestion of Carbohydrates
• Monosaccharides – Do not require hydrolysis before absorption
• Di- and poly-saccharides – Must be hydrolyzed prior to absorption – Most hydrolyzed to monosaccharides
Monosaccharides can be absorbed at brush border! Overview of Carbohydrate Digestion 2 Types of enzymes in the digestion of carbohydrates
Amylase Disaccharidases
Convert disaccharides to Convert polysaccharides to monosaccharides for disaccharides absorption Salivary Maltase amylase Sucrase-Isomaltase Pancreatic amylase Lactase
Trehalase Carbohydrate Digestion -Mouth • Begins in mouth – Chewing releases saliva and salivary amylase • Synthesized in serous cells of the salivary glands • Regulated by neurohumoral signals • Increased secretion when diet is high in carbohydrates • Breaks down starch at α1,4 linkages into polysaccharides and maltose • 5% of starch is broken down due to limited exposure – Amylase sensitive to acid pH Image from Dr Droual: http://droualb.faculty.mjc.edu/Course%20Materials/Physiology%20101/Chapter%2 0Notes/Fall%202007/chapter_20%20Fall%202007%20Phy%20101.htm Carbohydrate Digestion -Mouth • Clinical correlation – Salivary amylase has increased importance in a few clinical scenarios • Infants – Low levels of pancreatic enzymes in the first year • Pancreatic insufficiency – i.e. – Cystic Fibrosis – Breast milk contains amylase • Increased role in neonates and premature infants with low pancreatic amylase production Carbohydrate Digestion -Stomach
• Minimal carbohydrate digestion occurs in the stomach. • No enzymes available to break down starch. • Digestion by salivary amylase continues only until food mixed with acidic stomach secretions. – Low pH inhibits amylase activity • Gastric HCl hydrolyzes small amount of sucrose to fructose and glucose Carbohydrate Digestion -Intestine
• Small intestine – Majority of carbohydrate digestion takes place in small intestine (SI) – Pancreatic amylase is released • Secreted by pancreatic acinar cells • Secreted following stimulus of secretin and CCK • Targets α1,4 bonds • Terminal bonds and α1,6 bonds resist digestion – Starch in SI is digested into a mixture (simplest structures derived from branched amylopectin) • Maltose (glucose dimer) • Maltotriose (glucose trimer) • α –Limit dextrins (branched amylopectin remnants)
Image from: www.quizlet.com Carbohydrate Digestion -Intestine
– Oligosaccharides and disaccharides are digested at the brush border. • Further digestion required for all, but monosaccharides
– Specific enzymes finish the job • Enzymes are synthesized in the enterocytes and trafficked to the apical membranes • Enzymes are glycosylated in Golgi apparatus to protect from proteolysis • Anchored by trans-membrane segment • Higher concentration of enzymes in the proximal SI • Higher concentration on villi and lower in crypts
– Enzymes • Lactase – lactose into glucose and galactose • Sucrase – sucrose into glucose and fructose • Isomaltase – α1,6 bonds of limit dextrins • Maltase – Maltose into glucose and glucose Image from: www.wikipedia.com Sucrose • Sucrose = Table sugar – No luminal digestion – Brush border digestion by sucrase • Product is glucose and fructose – Rate limiting step is the uptake at apical membrane
Image from: http://www.indiana.edu/~oso/Fructose/Sources.html Lactose
• Lactose is a disaccharide consisting of glucose and galactose • Brush border digestion by lactase – 2 identical active sites with a single polypeptide chain • Glucose and galactose collect against concentration gradient • Rate limiting step is hydrolysis • Clinical correlation – Decreasing lactase with age – Lactase is inhibited by glucose
Image from: http://www.indiana.edu/~oso/Fructose/Sources.html Maltose
• Breakdown product of starch • Maltose is a disaccharide consisting of glucose and glucose • Brush border digestion by maltase Digestion in Large Intestine • Non-digestible carbohydrates – 10% starches, cellulose and hemicellulose from fruit and vegetables, some lactose and fructose, and monosaccharides lactulose, sorbitol and sucrulose • Limited mainly to anaerobic fermentation by colonic bacteria • Short-chain fatty acids produced by microbial digestion of fiber and undigested carbohydrates – Propionate – Butyrate – Acetate – Lactate • Methane and hydrogen also produced = flatus Carbohydrate Absorption
• Glucose is absorbed in the mouth in small quantities • No significant absorption occurs in stomach • Majority of sugars are absorbed in small intestine at apical membrane and transferred out at basolateral membrane to portal circulation. • Carrier mediated due to size of molecules – active transport down Na+ gradient • glucose and galactose – facilitated diffusion • fructose • Passive transport in small amounts Carbohydrate Digestion/Absorption “coupling”
Image from: Tsai - http://www.studyblue.com/notes/note/n/ph3-05- 06-digestion-and-absorption/deck/1101242 Glucose Absorption • Glucose absorption via SGLT-1 transporter – Active transport – Sodium-glucose co-transporter – Accumulate glucose against the gradient
Image from: Wright. Am J Phsy 1998 Fructose Absorption
• Fructose uses Glut5 and Glut2 – Na-independent – Facilitated diffusion
GLUT5
Image from: Wright. Am J Phsy 1998 Passive Transport
From: Breves. Livestock Science 2010 Regulation of Carbohydrate Absorption
• All enzymes and transporters are present at birth • Lactase activity is hard wired – Lactase persistence • Lactase remains at infantile levels – Lactase non-persistence • Lactase decreases starting at 3-5 years of age • Varies with race and ethnicity • Sucrase-isomaltase (SI) and maltase-glucoamylase levels are inducible – Transcriptional regulation mechanism Control of enzyme secretion
• Sucrase-isomaltase (SI) – 5’ flanking region of the SI gene has several DNA regulatory regions that control the initiation of gene transcription. – Transcriptional proteins • hepatocyte nuclear factor (HNF-1), GATA-type zinc finger transcription factors, and caudal-related homeodomain proteins (Cdx). – Hormonal influences have also been proposed and are currently being studied further.
• Lactase – Cdx, HNF-1 and GATA 5, along with other transcription factors all interact with the proximal promoter region and result in transcription initiation. – Possible repressor region exists that down regulates lactase expression. Lactase persistent people failed to bind at this repressor region due to single nucleotide polymorphisms (SNP). Clinical Correlations
• Glucose-Galactose Malabsorption – Mutation of SGLT-1 • Defective transporter – Severe diarrhea at birth • Osmotic diarrhea due to glucose and galactose malabsorption – FTT and malnutrition – Very rare – Treatment is fructose containing formula Congenital Sucrase-Isomaltase Deficiency
• Congenital Sucrase-Isomaltase Deficiency – Homozygous or heterozygous mutation in the SI gene • Autosomal recessive – 1 in 5,000 North Americans, 10% Eskimos – Maldigestion of sucrose and maltose – Presentation – osmotic diarrhea, abdominal pain and FTT – Treatment – • Sucrose and starch free diet. • Slowly introduce starch when sucrose free • Sucraid supplementation Clinical Correlations
• Small Bowel Bacterial Overgrowth – Increased bacteria Increased fermentation – Bacterial fermentation prevents small bowel absorption – Breath test - malabsorption results in increased breath H+ Clinical Correlations
• Pancreatic Insufficiency – Cystic fibrosis, pancreatitis, obstruction (tumor) • Mechanisms – Decreased enzyme volume • <10% baseline before symptoms – Failure to alkalinize fluid in small intestine • Enzymes are inactivated in acidic environment = malabsorption Clinical Correlations
• Celiac disease – Decreased absorptive capacity secondary to decreased villus length – Decreased enzymes due to decreased brush border surface area – Decreased number of transporters – Malabsorption and diarrhea Summary
• Carbohydrates are the major exogenous source of glucose • Three main types – Monosaccharides, disaccharides, and complex carbohydrates • Digestion requires a series of steps – Salivary and pancreatic amylase – Brush border enzymes • Non-digested carbohydrates are digested in the colon creating SCFA Review Questions: A 9y.o Asian boy is brought to your office by his mother. They report that he has had worsening diarrhea for the past 6 months following a viral acute gastroenteritis. What is the most likely reason for his diarrhea? Celiac disease Lactose Non-persistence Pancreatic Insufficiency Infection
What enzymes involved in carbohydrate digestion are induced by increasing dietary intake? A. Lactase B. Sucrase-isomaltase C. Maltase-glucoamylase D. Amylase Questions?
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