Absorption and digestion of carbohydrates CHO taken in diet are: polysaccharides, disaccharides monosaccharides These are supplied from external sources, hence called exogenous CHO These may be digestible or indigestible
Digestion of CHO takes place in; mouth stomach Intestine and absorption takes place form small intestine
Mouth At slightly acidic pH amyalse (ptyalin) acts on starch , which is converted into maltose and isomaltose The enzyme get inactivated in stomach 2(C6H10O5)n + nH2O nC12H22O11 starch maltose and isomaltose
Stomach• HCl can cause hydrolysis of starch into maltose and isomaltose and that of maltose to glucose but the reaction is of little significance inside stomach Small intestineIn small intestine pancreatic amylase converts 87% starch to maltose and isomaltose and 13 % glucose (C6H10O5)n + nH2O nC6H12O6
Disaccharides present in brush border of epithelial cells are lactose, sucrose, maltose and isomaltose. Lactase, sucrase, maltase and isomaltase hydrolyze disaccharides into their components as: Sucrose into glucose and fructose Maltose into glucose Lactose into glucose and galactose
Absorption Glucose 80-85% and few disaccharides are absorbed from small intestine through capillaries of intestinal mucosa The order of ease of absorption of monosaccharides is galactose > glucose > fructose > mannose > pentose
Mechanism of absorption Simple diffusion Active transport Factors upon which absorption of CHO depends are given as: Physical factors (how long food stays in intestine) Hormone thyroid hormones increase the rate of absorption hormones of adrenal cortex facilitate absorption
Facts about absorption of monosaccharides Chemical nature of most actively transported monosaccharides has following features in the choice of the carrier: Presence of 6 and more carbon atoms D-pyarnose structure Intact OH at carbon 2
Glucose and glycogen are broken down in the body by a complex chain of reactions catalyzed by many enzymes There are many metabolic pathways by which glucose can be utilized in the body; the most important one is Embden-Meyerhof pathway followed by citric acid cycle Glycolysis is of two types: anaerobic and aerobic
Anaerobic glycolysis Glucose is broken into two molecules of pyruvic acid It takes place in cytosol (extra-mitochondrial) The pyruvic acid is converted into lactic acid by utilizing NADH/H+ It can not continue indefinitely, lactic acid lowers the pH to a level that is not suitable for cellular function. On the other hand NADH/H+ became unavailable if aerobic metabolism remain suspended for a long time
Aerobic glycolysis In the presence of oxygen the pyruvic acid is formed in the same way as anaerobic glycolysis but it does not give rise to lactic acid Pyruvic acid is converted into acetyle-CoA which enters in citric acid cycle Reactions of citric acid cycle occur in mitochondria.
Main Features Oldest of Pathways Occurs in Soluble Phase of Cytoplasm (Cytosol) Anaerobic Phase of Energy Metabolism Generates ATP Produces Pyruvate/Lactate Produces Many Important Intermediates
Relationship to Other Pathways TCA Cycle Gluconeogenesis (in Liver and Kidney) Hexose Monophosphate Shunt (HMP) Metabolism of other Sugars, e.g., Fructose and Galactose Metabolism of Certain Amino Acids Lipid Metabolism Glycoprotein Synthesis
Transport of glucose into the cell Transportation of glucose is mediated by two types of systems that are given as follows:1- Insulin-independent transport system hepatocytes, erythrocytes and brain cells do not need insulin for entry of glucose into the cells. Transport occurs by a protein, which is an oligomer (MW 200,000) containing 4 sub-units of equal size2- Insulin-dependent transport system It occurs in muscles and adipose tissue cells. The binding of insulin to the receptors enhances the transport of glucose into cell by causing migration of glucose transport protein from microsomes to plasma membrane and by increasing transport capacity of the transport proteins
Glycolysis (Embden-Meyerhof pathway) 6 CH OPO 2− 2 3 5 O H H H 4 H 1 OH OH OH 3 2 H OH glucose-6-phosphate Glycolysis takes place in the cytosol of cells. Glucose enters the glycolysis pathway by conversion to glucose-6-phosphate. Initially there is energy input corresponding to ATP.
6 CH2OH 6 CH OPO 2− 2 3 ATP ADP 5 O 5 O H H H H H H 4 1 4 H 1 OH H OH Mg2+ OH OH OH OH 3 2 3 2 H OH Hexokinase H OH glucose glucose-6-phosphate1. Hexokinase catalyzes: Glucose + ATP glucose-6-P + ADPThe reaction involves nucleophilic attack of C-6hydroxyl O of glucose on P of the terminalphosphate of ATP. ATP binds to the enzyme as acomplex with Mg++.
NH2 ATP N N adenosine triphosphate N O O O N − O P O P O P O CH2 adenine O − − − H H O O O H H OH OH riboseMg++ interacts with negatively charged phosphateoxygen atoms, providing charge compensation &promoting a favorable conformation of ATP at theactive site of the Hexokinase enzyme.
6 CH2OH 6 CH OPO 2− 2 3 ATP ADP 5 O 5 O H H H H H H 4 1 4 H 1 OH H OH Mg2+ OH OH OH OH 3 2 3 2 H OH Hexokinase H OH glucose glucose-6-phosphateThe reaction catalyzed by Hexokinase is highlyspontaneous.A phosphate bond of ATP (~P) is cleaved.The phosphate ester formed - glucose-6-phosphate- has a lower ∆G of hydrolysis.
6 CH OPO 2− 2 3 5 6 CH OPO 2− 1CH2OH H O H 2 3 O H 4 H 1 5 H HO 2 OH OH OH H 4 3 OH 3 2 OH H H OH Phosphoglucose Isomerase glucose-6-phosphate fructose-6-phosphate2. Phosphoglucose Isomerase catalyzes: glucose-6-P (aldose) fructose-6-P (ketose)
Phosphofructokinase 6 CH OPO 2− 1CH2OH 6 CH OPO 2− 1CH2OPO32− 2 3 2 3 O ATP ADP O 5 H HO 2 5 H HO 2 H 4 3 OH Mg2+ H 4 3 OH OH H OH H fructose-6-phosphate fructose-1,6-bisphosphate3. Phosphofructokinase catalyzes: fructose-6-P + ATP fructose-1,6-bisP + ADPThe Phosphofructokinase reaction is the rate-limiting step of Glycolysis.
2− 1CH2OPO3 2C O H O HO 3C H Aldolase 3 CH2OPO32− 1C H 4C OH 2C O + H 2C OH 2− H C OH 1CH2OH 3 CH2OPO3 5 6 CH2OPO32− dihydroxyacetone glyceraldehyde-3- phosphate phosphate fructose-1,6- bisphosphate Triosephosphate Isomerase4. Aldolase catalyzes:fructose-1,6-bisphosphate dihydroxyacetone-P + glyceraldehyde-3-PThe reaction is an aldol cleavage, the reverse of an aldolcondensation.
2− 1CH2OPO3 2C O H O HO 3C H Aldolase 3 CH2OPO32− 1C H 4C OH 2C O + H 2C OH 2− H C OH 1CH2OH 3 CH2OPO3 5 6 CH2OPO32− dihydroxyacetone glyceraldehyde-3- phosphate phosphate fructose-1,6- bisphosphate Triosephosphate Isomerase5. Triose Phosphate Isomerase catalyzes: dihydroxyacetone-P glyceraldehyde-3-P
Triosephosphate Isomerase H H OH H + O + + + H C OH H H C H H C C O C OH H C OH CH2OPO32− CH2OPO32− CH2OPO32− dihydroxyacetone enediol glyceraldehyde- phosphate intermediate 3-phosphateThe ketose/aldose conversion involves acid/basecatalysis, and is thought to proceed via an enediolintermediate, as with Phosphoglucose Isomerase.
Glyceraldehyde-3-phosphate Dehydrogenase H O + H+ O OPO32− 1C NAD+ NADH 1C + Pi H C OH H C OH 2 2 3 CH2OPO32− 3 CH2OPO32− glyceraldehyde- 1,3-bisphospho- 3-phosphate glycerate6. Glyceraldehyde-3-phosphate Dehydrogenasecatalyzes: glyceraldehyde-3-P + NAD+ + Pi 1,3-bisphosphoglycerate + NADH + H+
Phosphoglycerate Kinase O OPO32−ADP ATP O O− 1C C 1 H C 2 OH H C 2 OH 2− Mg2+ 3 CH2OPO3 3 CH2OPO32− 1,3-bisphospho- 3-phosphoglycerate glycerate7. Phosphoglycerate Kinase catalyzes: 1,3-bisphosphoglycerate + ADP 3-phosphoglycerate + ATP
Phosphoglycerate Mutase O O− O O− C 1 C 1 H 2C OH H 2C OPO32− 2− 3 CH2OPO3 3 CH2OH3-phosphoglycerate 2-phosphoglycerate8. Phosphoglycerate Mutase catalyzes: 3-phosphoglycerate 2-phosphoglyceratePhosphate is shifted from the OH on C3to the OH on C2.
Enolase − O H+ − − O OH− O− O O O C C 1 C 1 H 2 C OPO32− C OPO32− 2C OPO32− 3 CH2OH CH2OH 3 CH2 2-phosphoglycerate enolate intermediate phosphoenolpyruvate9. Enolase catalyzes: 2-phosphoglycerate phosphoenolpyruvate +H2OThis dehydration reaction is Mg++- dependent.
Pyruvate Kinase O O− O O− ADP ATP C 1 1 C 2 C OPO32− 2 C O 3 CH2 3 CH3 phosphoenolpyruvate pyruvate10. Pyruvate Kinase catalyzes: phosphoenolpyruvate + ADP pyruvate + ATP
Pyruvate Kinase O O− O O− O O− C ADP ATP C C 1 1 1 2 C OPO32− C 2 OH 2 C O 3 CH2 3 CH2 3 CH3 phosphoenolpyruvate enolpyruvate pyruvateThis phosphate transfer from PEP to ADP is spontaneous. Removal of Pi from PEP yields an unstable enol, which spontaneously converts to the keto form of pyruvate.
glucose Glycolysis ATP Hexokinase ADP glucose-6-phosphate Phosphoglucose Isomerase fructose-6-phosphate ATP Phosphofructokinase ADP fructose-1,6-bisphosphate Aldolaseglyceraldehyde-3-phosphate + dihydroxyacetone-phosphate Triosephosphate Isomerase Glycolysis continued
glyceraldehyde-3-phosphateNAD+ + Pi Glyceraldehyde-3-phosphateNADH + H+ Dehydrogenase 1,3-bisphosphoglycerate ADP Phosphoglycerate Kinase ATP 3-phosphoglycerate Phosphoglycerate Mutase 2-phosphoglycerate H2O Enolase phosphoenolpyruvate ADP Pyruvate Kinase ATP pyruvate
Lactate Dehydrogenase O O− O O− C NADH + H+ NAD+ C C O HC OH CH3 CH3 pyruvate lactateE.g., Lactate Dehydrogenase catalyzes reduction of the keto to enol,yielding lactate, as NADH is oxidized to NAD+.
Glycogen Glucose Hexokinase or Glucokinase Glucose-6-PaseGlucose-1-P Glucose-6-P Glucose + Pi Glycolysis Pathway Pyruvate Glucose metabolism in liver.
Energy from glycolysis ATP consumed 2 moles ATP produced direct 4 moles ATP indirect (NADH/H) 6 moles Net ATPs = 10-2= 8 moles If anaerobic glycolysis 2 moles
Glycogen Glucose Hexokinase or Glucokinase Glucose-6-Pase Glucose-1-P Glucose-6-P Glucose + Pi Glycolysis Pathway Pyruvate Glucose metabolism in liver.Glucose-6-phosphatase catalyzes hydrolytic release of Pi fromglucose-6-P. Thus glucose is released from the liver to theblood as needed to maintain blood glucose.The enzymes Glucokinase & Glucose-6-phosphatase, bothfound in liver but not in most other body cells, allow the liverto control blood glucose.