Absorption GENERAL PRINCIPLES• Breakdown of complex molecules – Enzymes (pH)• Absorption into gut cells – Mechanism of absorption – Active [energy] – Passive [no direct energy ] – carriers SF Biology II 4
Absorption of Carbohydrates Essentially all CHO are absorbed in the form of monosaccharides 80% glucose 20% fructose and galactose All monosaccharides absorbed by active transport. Glucose transported by sodium co-transport mechanism Galactose similar to glucose Fructose transported by facilitated diffusion 5
FACILITATIVE GLUCOSETRANSPORTERS Transporter Tissue Distribution Human erythrocyte Blood-brain barrier GLUT 1 Blood-retinal barrier Blood-placental barrier Blood-testis barrier Liver GLUT 2 Kidney Pancreatic β-cell Serosal surface of intestinal mucosal cells
FACILITATIVE GLUCOSETRANSPORTERS Transporter Tissue Distribution GLUT 3 Brain (neurons) Major transporter in the CNS Adipose tissue GLUT 4 Skeletal muscle Heart muscle GLUT 5 Intestinal epithelium (fructose Spermatozoa transporter)
PATHOLOGICAL CONDITIONS AFFECTING DIGESTIONAND ABSORPTION OF CARBOHYDRATESI. Disaccharidase Deficiences A. Hereditary – with genetic basis B. Acquired – temporary decrease of enzymes from prolonged or severe diarrhea, malnutrition or drugs Ex. 1. Lactase deficiency - intolerance to lactose or dairy products Types: i. Inherited lactase deficiency – develops soon after birth with lactose feeding ii. Primary low lactase activity – seen among adult Blacks & Orientals or Asians, hence milk is not part of their food.
PATHOLOGICAL CONDITIONS AFFECTING DIGESTION AND ABSORPTION OF CARBOHYDRATESI. Disaccharidase Deficiences B. Acquired Ex. 1. Lactase Deficiency Types: iii. Secondary low lactase activity – from intestinal diseases that injure the lactase-producing intestinal villi: colitis, gastroenteritis & excessive alcohol intake. 2. Isomaltase – sucrase Deficiency = intolerance to ingested isomaltose and sucrose
PATHOLOGICAL CONDITIONSAFFECTING DIGESTION ANDABSORPTION OFCARBOHYDRATESII. Monosaccharide Malabsorption – congenital defect in Na-glucose co- transporter carrier mechanism, hence glucose and galactose are absorbed only slowly.
PATHOPHYSIOLOGY OF LACTOSE INTOLERANCE Unabsorbed lactose in large intestine attracts H2O (osmotic agent) Bacterial fermentation H2, CO2, CH4 diarrhea nausea bloating dehydration flatulence metabolic acidosis
LACTOSE INTOLERANCE:TREATMENTA. Reduction or avoidance of lactose- containing foods.B. Use of hard cheeses (Cheddar, Swiss, Jalsbey) – low in lactoseC. Yogurt – with live bacteria that release free lactases when the bacteria are released by gastric acid and proteolytic enzymes.D. Lactate tablet/capsule, Lactaid® - should be taken 1 hr. before meals
GLYCOLYSISI. Other Name: Embden-Meyerhoff PathwayII. Function: the major pathway for glucose utilization (and for fructose and galactose) to provide energy (ATP)III. Site: Cytoplasm of all cells (or in the extra mitochondrial soluble fraction of the cell)IV. Types A. Aerobic – uses oxygen; pyruvate is the end product B. Anaerobic – uses no oxygen; lactate is the end product
GLYCOLYSISV. Phases A. First Phase - first 5 reactions - energy investment phase because ATP is utilized in the synthesis of phosphorylated forms of glucose and fructose - preparatory or collection phase (Lehninger) bec. glucose and a no. of hexoses like fructose, galactose and mannose and the pentoses after phosphorylation by ATP undergo catabolism and then cleaved to form glyceraldehyde 3-phosphate.
GLYCOLYSISV. Phases B. Second Phase - last 5 reactions - energy generation phase or payoff phase because two (2) molecules of ATP are formed per molecule of glucose oxidized to pyruvate or lactate.
GLYCOLYSIS: Reactions 1. Phosphorylation of Glucose O O || Hexokinase || C1 - H or C1 - H | Glucokinase | H - C2 - OH (Liver, Pancreatic β cells) H - C2 - OH | | OH - C3 - H Mg+2 OH - C3 - H | | H - C4 - OH H - C4 - OH | ATP ADP | H - C5 - OH H - C5 - OH | | H - C6 – OH Δ G0 = - 4.0 kcal/mole H - C6 - O – P | | H H Glucose 6-Phosphate Glucose
GLYCOLYSIS: Reactions 2. Isomerization of Glucose 6-Phosphate O Aldehyde group H || | C1 - H H - C - OH | | Keto group H - C2 - OH C2 = O | | OH - C3 - H Phosphohexose isomerase OH - C3 - H | | H - C4 - OH H - C4 - OH | | H - C5 - OH H - C5 - OH | | H - C6 - O – P Δ G0 = + 4.0 kcal/mole H - C6 - O – P | | H HGlucose 6-Phosphate Fructose 6-Phosphate (Aldose) (Ketose)
GLYCOLYSIS: Reactions 3. Phosphorylation of Fructose 6-Phosphate H H | | H - C1 - OH H - C1 - O - P | | C2 = O C2 = O Phosphofructokinase I | | OH - C3 - H OH - C3 - H | Mg+2 | H - C4 - OH H - C4 - OH | | H - C5 - OH ATP ADP H - C5 - OH | | H - C6 - O – P H - C6 - O – P | Δ G0 = - 3.4 kcal/mole | H HFructose 6-Phosphate Fructose 1, 6-Bisphosphate
GLYCOLYSIS: Reactions 4. Cleavage of Fructose 1,6-Bisphosphate P P | | O O H OH OH O | || | | | | H - C1 – C2 – C3 - C4 - C5 - C6 - H Aldolase A | | | | | H OH H H H Fructose 1,6-Bisphosphate O O || || H – C1 – H H – C4 – O – P | | Δ G0 = + 5.73 kcal/mole H – C2 – OH H – C5 – OH | | H – C3 – O – P Triose phosphate isomerase H – C6 – OH | | H H Glyceraldehyde Δ G0 = +1.83 kcal/mole Dihydroacetone 3 - Phosphate Phosphate (DHAP)
GLYCOLYSIS: Reactions 5. Oxidation of Glyceraldehyde 3- Phosphate NAD+ NADH + H+ O Pi O || H – C1 – H || | C1 – O ~ P H – C – OH | Glyceraldehyde 3-phosphate | H – C – OH dehydrogenase H – C3 – O – P | | H – C3 – O – P H | Δ G0 = + 1.5 kcal/mole HGlyceraldehyde 1,3-Bisphosphoglycerate3 - Phosphate
GLYCOLYSIS: Reactions 6. Formation of ATP from 1,3- Bisphosphoglycerate O O || || C1 – O ~ P C1 – O- | | Phosphoglycerate kinase H – C – OH H – C – OH | | H – C3 – O – P H – C3 – O – P | | H ADP ATP H1,3-Bisphosphoglycerate 3 - Phosphoglycerate Δ G0 = + 1.06 kcal/mole
GLYCOLYSIS: Reactions 7. Isomerization of 3-phosphoglycerate to 2-phosphoglycerate O O || || C1 – O- C1 – O- | | H – C2 – OH H – C2 – O - P | Phosphoglycerate mutase | H – C3 – O – P H – C3 – OH | Mg+2 | H H3-Phosphoglycerate 2-Phosphoglycerate Δ G0 = + 1.06 kcal/mole
GLYCOLYSIS: Reactions 8. Dehydration of 2-Phosphoglycerate O O || || C1 – O - C1 – O - | Enolase | H – C2 – O - P C2 – O ~ P | | Mg+2 H20 H – C3 H – C3 – OH | | H H2-Phosphoglycerate Phosphoenol Pyruvate (PEP) Δ G0 = + 0.44 kcal/mole
GLYCOLYSIS: Reactions 9. Formation of Pyruvate O || C1 – O- | Pyruvate kinase COO- C2 – O ~ P | | C2 = O Mg+2 H – C3 | K+ | CH3 H ADP ATPPhosphoenol Pyruvate Pyruvate (PEP) Δ G0 = - 6.1 kcal/mole
GLYCOLYSIS: Reactions10. Conversion of Pyruvate to Acetyl CoA Under Aerobic Conditions Glucose 2ADP + Pi 2NAD+ 2ATP NADH+ + H+ 2 Pyruvate Pyruvate Dehydrogenase Acetyl CoA ETC NADH TCA Cycle FADH2 Mitochondrion
FATES OF PYRUVATE Pyruvate Aerobicconditions NADH Anaerobic NADH Anaerobic conditions Pyruvate conditionsdehydrogenase NAD+ Pyruvate NAD+ carboxylase Acetyl CoA Lactate Ethanol Anaerobic glycolysis + in contracting muscles CO2 Alcoholic fermentation TCA in yeasts cycle CO2 + H2O Animals and plants
GLYCOLYSIS: Reactions10. Reduction of Pyruvate to Lactate Under Anaerobic Conditions NADH + H+ NAD+ COO- Lactate COO- | Dehydrogenase | C2 = O H - C2 – OH | | CH3 CH3 NADH + H+ NAD+ Pyruvate Lactate Δ G0 = - 6.0 kcal/mole
GLYCOLYSIS: Reactions 10. Conversion to Ethanol CO2 Pyruvate Ethanol Pyruvate decarboxylase 1. Occurs in some cells, like yeasts 2. Pathway has commercial roles in beer and bread manufacture. a. In the brewery, the CO2 is captured to carbonate the final alcoholic brew, hence this gas produces the foamy head. b. In the bakery, CO2 is the agent that causes bread dough to rise. 3. Mammals lack pyruvate decarboxylase hence cannot produce ethanol from pyruvate.
ATP YIELD OF GLYCOLYSIS ATP1. Glucose Glucose 6-PO4 -12. Fructose 6-PO4 Fructose 1,6 bisPO4 -13. Glyceraldehyde 3-PO4 3-phosphoglycerate +2 (per glucose)4. PEP Pyruvate +2 (per glucose) Net ATP Production +2 (per
SUMMARY OF GLYCOLYSIS Hexokinase Phosphohexo glucokinase isomerase Glucose Glucose 6-Phosphate Fructose 6-PO4 Mg+2 ATP Phospho ATP ADP Mg++ fructo ADP Kinase I Fructose 1,6-Bisphosphate Phospho Glyceraldehyde 3-Phospho- glycerate 3-Phosphate glycerate kinase Dehydrogenase Aldolase A Phospho Glyceraldehyde ATP 1,3-Bisphospho Dihydroacetone glycerate 3-Phosphate mutase ADP glycerate Pi Triosephosphate Phosphate isomerase 2 - Phosphoglycerate NAD+ Mg+2 NADH + H+ Enolase ½ O2 H2O Resp. chainPhosphoenol Pyruvate Anaerobiosis H20 ADP Pyruvate kinase NADH + H + NAD + 3 ADP + Pi 3ATP ATP Pyruvate Lactate Lactate dehydrogenase Acetyl CoA CO2 + H20 (CAC)