Digestion))&) Absorption Zharlah Gulmatico-Flores, MD, DPDS Department of Biochemistry and Nutrition
Objectives O Give insight on the digestion and absorption of the
main dietary categories in the human body and the key metabolic processes occurring in the human body that could contribute to the understanding and explanation of the pathological phenomena.
O Integrate the knowledge in anatomy and physiology
involved in the compartments in which digestion and absorption occurs.
Objectives Know the involved enzymes, its location and secretory mechanisms. O Understand the metabolic fate of some substances that cannot be digested. O Correlate clinically the disorders arising from the inability to digest carbohydrates, proteins and fats. O Identify the interactions between these major metabolic pathways and the molecular basis of the control of these pathways. O
Digestion and Absorption of Carbohydrates
Carbohydrate Digestion
Carbohydrates1 ✤ Simple sugars, disaccharides, and complex
carbohydrates. ✤ Not essential in the diet. ✤ 40 to 45% of the total daily diet. ✦ 30 to 40% are oligosaccharides. ✦ 50 to 60% are plant starches. ✓ amylose and amylopectin ✓ glycogen
Goodman.Insights into digestion and absorption of major nutrients in humans. Adv Physio Educ.34.44.2010.
Carbohydrates Salivary glands
ÂŁ - amylase endosaccharidases
30 to 40%
Acid pH Small intestine
ÂŁ - 1,4 glycosidic bonds Bicarbonate pancreatic amylase Secretin
Brush border
exoenzymes
Intestinal brush border enzymes
β -glucoamylase
β glycosidase complex
Sucrase-isomaltase complex
Trehalase
β glycosidic bonds, Lactose
Maltose
Maltose, Maltotriose, Sucrose
KINDLY correct your notes regarding: B-glucoamylase, it hydrolyzes alpha 1,4 glycosidic bonds.
Trehalose
Enzymes Site
Enzymes
Mouth
£ - amylase
Duodenum
Pancreatic £-amylase, trehalase
Proximal jejunum
Sucrase-isomaltase, βglycosidase
Proximal ileum
β- Glucoamylase Goodman.Insights into digestion and absorption of major nutrients in humans. Adv Physio Educ.34.46.2010.
Carbohydrate Absorption
Wright EM, Hirayama BA, Loo DDF, et al: Intestinal sugar transport. Physiology of the Gastrointestinal Tract, 3rd ed. New York, Raven Press, 1994, p 1752.
Glucose1Transport1Proteins Glucose transporter
Site
GLUT 2
all tissues of the body, esp. in RBC, and blood vessels of the brain kidneys, intestines and liver
GLUT 3
neurons, placenta, testes.
GLUT 4
skeletal muscle, cardiac muscle and fat
GLUT 5
skeletal muscle, testis, spermatozoa kidney and fat tissue
GLUT 1
Clinical Correlation
Balen MD, Osmotic Diarrhea. 2007
Digestion and Absorption of Protein
Protein Digestion
Protein Total daily protein load is 70 to 100 g of dietary protein O 35 to 200g of endogenous proteins, including the digestive enzymes and dead cells. O Endopeptidases attack internal bonds and result in large polypeptides. O Exopeptidases cleave off one amino acid at a time. O
Protein Pepsin
Stomach
endopeptidase
HCl GIP
10-15 %
Small intestine
Aromatic amino acids Bicarbonate Pancreatic proteases Secretin
Brush border
GASTRIN, as hormone in the presence of chyme in the stomach would stimulate the secretion of Gastric acid (HCl, secreted by the parietal cells) alters the conformation of pepsinogen so that it can cleave itself and become active pepsin in the stomach. GIP - inhibits the churning movement of stomach as the food enters the small intestine. Secretin produced by the duodenal cells would be activated and then stimulate the pancreas to get it itself ready to secrete pancreatic juice and stimulate the liver to secrete bile. CCK - stimulates the release of pancreatic juice and contraction of gall bladder.
Intestinal brush border
Elastase
Trypsin
Carboxypeptidase
Chymotrypsin Arg and Lys
Aminopeptidase
Ala, Gly and Ser
NH terminus
Hydrophobic amino acids Val, Leu, Ile, Ala, Arg, Lys
Enzyme Pepsin Trypsin Chymotrypsin Elastase
Activated by
Action
Cleavage Points
Endopeptidase Tyr, Phe, Leu and
Asp Enteropeptidase Endopeptidase Arg and Lys and trypsin Endopeptidase Tyr, Trp, Phe, Met Trypsin and Leu Endopeptidase Ala, Gly and Ser Trypsin
Carboxypeptidase A
Trypsin
Exopeptidase
Carboxypeptidase B
Trypsin
Exopeptidase
Aminopeptidases
ERRATUM: Enterokinase - is also known as enteropeptidase.
Exopeptidase
Val, Leu, Ile and Ala Arg, and Lys
Protein Absorption
Amino1acid1transporters O
General properties: Stereospecificity O Broad substrate specificity O Overlapping specificity O
O Main functional criteria:
Type of amino acid transported O Transport mechanism used O
Amino acids Na-dependent Active Transport
Enterocyte Na-independent Active Transport
Capillary
Clinical Correlation
Hartnup1disease Mutation on amino acid transport. O Defective intestinal and renal transport of neutral amino acids involving System B. O Pellagra like skin changes, cerebellar ataxia, and psychiatric abnormalities. O
Digestion and Absorption of Fats
Fats 30 to 40% of the calories in typical diet. O >90% of the ingested fats is in the form of triglycerides. O Dietary fatty acids found in food are long chain fatty acids. O Medium-chain fatty acids are rarely found in food. O
Fat Digestion
Fats Lingual lipase
Trypsin
Lingual glands Gastrin
CCK
15 to 20%
Stomach
Gastric lipase
Bile
GIP Small intestine
Pancreatic lipase Colipase Pancreatic esterase
GASTRIN, as hormone in the presence of chyme in the stomach would stimulate the secretion of Gastric acid (HCl, secreted by the parietal cells) alters the conformation of pepsinogen so that it can cleave itself and become active pepsin in the stomach. GIP - inhibits the churning movement of stomach as the food enters the small intestine. Secretin produced by the duodenal cells would be activated and then stimulate the pancreas to get it itself ready to secrete pancreatic juice and stimulate the liver to secrete bile. CCK - stimulates the release of pancreatic juice and contraction of gall bladder.
Fat Absorption
Fatty acids Diffusion
Enterocytes
FATP2 – FATP4, FAT/CD36
Triglycerides + Apo B48 + phospholipids
Golgi complex
Central lacteal lymph
Smooth ER
43
Clinical Correlation
45
Maldigestion,and,Malabsorption, of,fats O Gallstones O Pancreatitis O Cystic Fibrosis O Giardiasis
46
References Aronson PS, et al. Physiology of membranes. In: Medical Physiology: a Cellular and Molecular Approach, edited by Boron WF, Boulpaep EL. Philadelphia, PA: Saunders, 2003, p. 66–67. Binder HJ, Reuben A. Nutrient digestion and absorption. In: Medical Physiology: a Cellular and Molecular Approach, edited by Boron WF, Boulpaep EL. Philadelphia, PA: Saunders, 2009, p. 949–979. Daniel H. Molecular and integrative physiology of intestinal peptide transport. Annu Rev Physiol 66: 361–384, 2004. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Hoboken, NJ: Wiley-Liss, 2006. Murray RK., et al. Harper’s Illustrated Biochemistry 29th edition. Kuksis, et al Lipid absorption and Metabolism. Environ & Health Persp. 33:45-55.1979. Johnson LR. Essential Medical Physiology. Philadelphia, PA: Lippincott- Raven, 1998. Lieberman M, Marks AD. Basic Medical Biochemistry: a Clinical Approach. Baltimore, MD: Lippincott, Williams and Wilkins, 2009. Holmes, R. Carbohydrates Digestion and Absorption. J. Clin Path. 5:24S;10-13. Lowe ME. The triglyceride lipases of the pancreas. J Lipid Res 43: 2007–2016, 2002. Mansbach CM, Gorelick F. Development and physiological regulation of intestinal lipid absorption. II. Dietary lipid absorption, complex lipid synthesis, and the intracellular packaging and secretion of chylomicrons. Am J Physiol Gastrointest Liver Physiol 293: G645–G650, 2007. Manolescu AR, Witkowska K, Kinnaird A, Cessford T, Cheeseman C. Facilitated hexose transporters: new perspectives on form and function. Physiology22:234 –240, 2007. Sherwood L. Human Physiology: From Cells to Systems. Belmont, CA: Brooks/Cole, 2010. Southgate, D. Digestion and Absorption of Sugars. Am J Clin Nutr 1995;62:204S. Ernest, et al. Biology of Human Glucose Transporters. Physio Rev 91:733-794, 2011.
“Dis-moi ce que tu manges, je te dirai ce que tu es.�
Tell me what you eat and I shall tell you what you are. Physiologie du Gout, ou Meditations de Gastronomie Transcendante, 1826
Thank You !