Abosrption and metabolism of cho
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Transcript of Abosrption and metabolism of cho
CarbohydratesCarbohydrates
By Khuram AzizSenior Demonstrator
Junior sci, by IBCMember of NAYS
1
SF Biology II 2
Carbohydrate (CHO) DigestionCarbohydrate (CHO) DigestionIn lumenIn lumenStarch Starch maltose + maltriose + maltose + maltriose + αα-limit dextrins-limit dextrinsAmylaseAmylase
Carbohydrate digestion and Carbohydrate digestion and absorptionabsorptionAt brush-border• Maltose/maltriose glucose
– Glucoamylase (maltase)– Sucrase-isomaltase
• α-limit dextrins glucose– Sucrase-isomaltase
• Sucrose glucose + fructose– Sucrase-isomaltase
• Lactose glucose + galactose– Lactase
SF Biology II 3
SF Biology II 4
AbsorptionAbsorption
GENERAL PRINCIPLES
• Breakdown of complex molecules
– Enzymes (pH)
• Absorption into gut cells
– Mechanism of absorption
– Active [energy]
– Passive [no direct energy ]
– carriers
Essentially all CHO are absorbed in the form of monosaccharides
80% glucose20% fructose and galactose
All monosaccharides absorbed by active transport.Glucose transported by sodium co-transport mechanismGalactose similar to glucoseFructose transported by facilitated diffusion
Absorption of CarbohydratesAbsorption of Carbohydrates
5
6
7
Carbohydrate digestion and Carbohydrate digestion and absorptionabsorption
SGLT-1• Na+ coupled(Na/K ATPase for gradient)• D-hexoses w/ pyranose ring
apical basolateral
GLUT-5• Fructose absorption• Jejunum• Facilitated diffusion
GLUT-2
FACILITATIVE GLUCOSE FACILITATIVE GLUCOSE TRANSPORTERSTRANSPORTERS
TransporteTransporterr
Tissue DistributionTissue Distribution
GLUT 1GLUT 1
Human erythrocyteHuman erythrocyte
Blood-brain barrierBlood-brain barrier
Blood-retinal barrierBlood-retinal barrier
Blood-placental barrierBlood-placental barrier
Blood-testis barrierBlood-testis barrier
GLUT 2GLUT 2LiverLiver
KidneyKidney
Pancreatic Pancreatic ββ-cell-cell
Serosal surface of intestinal Serosal surface of intestinal mucosal cellsmucosal cells
FACILITATIVE GLUCOSE FACILITATIVE GLUCOSE TRANSPORTERSTRANSPORTERS
TransportTransporterer
Tissue DistributionTissue Distribution
GLUT 3GLUT 3 Brain (neurons)Brain (neurons)
Major transporter in the CNSMajor transporter in the CNS
GLUT 4GLUT 4Adipose tissueAdipose tissue
Skeletal muscleSkeletal muscle
Heart muscleHeart muscle
GLUT 5GLUT 5
(fructose (fructose transporter)transporter)
Intestinal epitheliumIntestinal epithelium
SpermatozoaSpermatozoa
PATHOLOGICAL CONDITIONS AFFECTING DIGESTION PATHOLOGICAL CONDITIONS AFFECTING DIGESTION AND ABSORPTION OF CARBOHYDRATESAND ABSORPTION OF CARBOHYDRATES
I. Disaccharidase DeficiencesA. Hereditary – with genetic basisB. Acquired – temporary decrease of enzymes
from prolonged or severe diarrhea, malnutrition or drugsEx. 1. Lactase deficiency - intolerance to
lactose or dairy productsTypes: 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 PATHOLOGICAL CONDITIONS AFFECTING DIGESTION AND ABSORPTION OF CARBOHYDRATESAND ABSORPTION OF CARBOHYDRATES
I. Disaccharidase DeficiencesB. Acquired
Ex. 1. Lactase DeficiencyTypes: 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 CONDITIONS PATHOLOGICAL CONDITIONS AFFECTING DIGESTION AND AFFECTING DIGESTION AND ABSORPTION OF ABSORPTION OF CARBOHYDRATESCARBOHYDRATES
II. Monosaccharide Malabsorption – congenital defect in Na-glucose co-transporter carrier mechanism, hence glucose and galactose are absorbed only slowly.
PATHOPHYSIOLOGY OF LACTOSE INTOLERANCEPATHOPHYSIOLOGY OF LACTOSE INTOLERANCE
Unabsorbed lactose in large intestine attracts H2O (osmotic agent)
Bacterial fermentation
H2, CO2, CH4
diarrhea nausea dehydrationbloating
flatulence metabolic acidosis
LACTOSE INTOLERANCE: LACTOSE INTOLERANCE: TREATMENTTREATMENTA. 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
GLYCOLYSISGLYCOLYSIS
I. 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. TypesA. Aerobic – uses oxygen; pyruvate is
the end productB. Anaerobic – uses no oxygen; lactate
is the end product
GLYCOLYSISGLYCOLYSISV. 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.
GLYCOLYSISGLYCOLYSISV. 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: ReactionsGLYCOLYSIS: Reactions
1. Phosphorylation of Glucose
Hexokinaseor
Glucokinase(Liver, Pancreatic β cells)
ATP ADP
Mg+2
Δ G0 = - 4.0 kcal/mole
O || C1 - H | H - C2 - OH |OH - C3 - H | H - C4 - OH | H - C5 - OH | H - C6 – OH | H
Glucose
O || C1 - H | H - C2 - OH |OH - C3 - H | H - C4 - OH | H - C5 - OH | H - C6 - O – P | HGlucose 6-Phosphate
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions2. Isomerization of Glucose 6-
Phosphate
(Aldose) (Ketose)
O || C1 - H | H - C2 - OH |OH - C3 - H | H - C4 - OH | H - C5 - OH | H - C6 - O – P | H
H | H - C - OH | C2 = O |OH - C3 - H | H - C4 - OH | H - C5 - OH | H - C6 - O – P | H
Phosphohexose isomerase
Aldehyde group
Keto group
Glucose 6-Phosphate Fructose 6-Phosphate
Δ G0 = + 4.0 kcal/mole
H | H - C1 - OH | C2 = O |OH - C3 - H | H - C4 - OH | H - C5 - OH | H - C6 - O – P | H
H | H - C1 - O - P | C2 = O |OH - C3 - H | H - C4 - OH | H - C5 - OH | H - C6 - O – P | H
Phosphofructokinase I
ATP ADP
Mg+2
Δ G0 = - 3.4 kcal/mole
Fructose 6-Phosphate
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
Fructose 1, 6-Bisphosphate
3. Phosphorylation of Fructose 6-Phosphate
4. Cleavage of Fructose 1,6-BisphosphateGLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
P P | | O O H OH OH O | || | | | |H - C1 – C2 – C3 - C4 - C5 - C6 - H | | | | | H OH H H H
Fructose 1,6-Bisphosphate O ||H – C1 – H |H – C2 – OH |H – C3 – O – P | H
O ||H – C4 – O – P |H – C5 – OH |H – C6 – OH | H
Glyceraldehyde3 - Phosphate
DihydroacetonePhosphate (DHAP)
Aldolase A
Triose phosphate isomerase
Δ G0 = +1.83 kcal/mole
Δ G0 = + 5.73 kcal/mole
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
5. Oxidation of Glyceraldehyde 3-Phosphate
O ||H – C1 – H |H – C – OH |H – C3 – O – P | H
O || C1 – O ~ P |H – C – OH |H – C3 – O – P | H
Glyceraldehyde3 - Phosphate
1,3-Bisphosphoglycerate
Glyceraldehyde 3-phosphatedehydrogenase
NAD+NADH + H+
Δ G0 = + 1.5 kcal/mole
Pi
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions6. Formation of ATP from 1,3-Bisphosphoglycerate
O || C1 – O-
|H – C – OH |H – C3 – O – P | H
O || C1 – O ~ P |H – C – OH |H – C3 – O – P | H
1,3-Bisphosphoglycerate 3 - Phosphoglycerate
Phosphoglycerate kinase
ADP ATP
Δ G0 = + 1.06 kcal/mole
7. Isomerization of 3-phosphoglycerate to 2-phosphoglycerate
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
O || C1 – O-
|H – C2 – O - P |H – C3 – OH | H
O || C1 – O-
|H – C2 – OH |H – C3 – O – P | H
3-Phosphoglycerate2-Phosphoglycerate
Phosphoglycerate mutase
Mg+2
Δ G0 = + 1.06 kcal/mole
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions8. Dehydration of 2-Phosphoglycerate
O || C1 – O-
| C2 – O ~ P |H – C3
| H
O || C1 – O-
|H – C2 – O - P |H – C3 – OH | H
2-Phosphoglycerate Phosphoenol Pyruvate(PEP)
Enolase
Mg+2H20
Δ G0 = + 0.44 kcal/mole
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
9. Formation of Pyruvate
COO-
| C2 = O | CH3
O || C1 – O-
| C2 – O ~ P |H – C3
| H
Phosphoenol Pyruvate(PEP)
Pyruvate
Pyruvate kinase
ADP ATP
Mg+2
K+
Δ G0 = - 6.1 kcal/mole
10. Conversion of Pyruvate to Acetyl CoA Under Aerobic Conditions
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
Glucose
2 Pyruvate
2NAD+
NADH+ + H+
2ADP + Pi
2ATP
Acetyl CoA
PyruvateDehydrogenase
TCACycle
NADH
FADH2
ETC
Mitochondrion
FATES OF PYRUVATEFATES OF PYRUVATE
PyruvateAerobic
conditions
Acetyl CoA Lactate Ethanol
Anaerobic conditions
Anaerobic conditions
NADH
NAD+
NADH
NAD+
TCAcycle
CO2 + H2O
Animals and plants
Anaerobic glycolysisin contracting muscles
+CO2
Alcoholic fermentation in yeasts
Pyruvatedehydrogenase Pyruvate
carboxylase
10. Reduction of Pyruvate to Lactate Under Anaerobic Conditions
GLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
COO-
| H - C2 – OH | CH3
COO-
| C2 = O | CH3
Pyruvate
NADH + H+ NAD+
NADH + H+ NAD+
LactateDehydrogenase
Lactate
Δ G0 = - 6.0 kcal/mole
10. Conversion to EthanolGLYCOLYSIS: ReactionsGLYCOLYSIS: Reactions
Pyruvate EthanolPyruvate
decarboxylase
CO2
1. Occurs in some cells, like yeasts2. 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 GLYCOLYSISATP YIELD OF GLYCOLYSIS
1. Glucose Glucose 6-PO4 -1
2. Fructose 6-PO4 Fructose 1,6 bisPO4 -1
3. Glyceraldehyde 3-PO4 3-phosphoglycerate +2 (per glucose)
4. PEP Pyruvate +2 (per glucose)
Net ATP Production +2 (per glucose)
ATP
SUMMARY OF GLYCOLYSISSUMMARY OF GLYCOLYSIS
Dihydroacetone Phosphate
Acetyl CoA
Glucose Glucose 6-Phosphate Fructose 6-PO4
Hexokinaseglucokinase
Phosphohexoisomerase
Mg+2
ATP ADP
Glyceraldehyde 3-Phosphate
Dehydrogenase
Phosphofructo
Kinase I
ATP
ADPMg++
Fructose 1,6-Bisphosphate
Aldolase AGlyceraldehyde
3-PhosphateTriosephosphate
isomerase
Pi
NADH + H+
NAD+
NADH + H+ NAD+
Anaerobiosis H20Resp. chain
3 ADP + Pi 3ATP
½ O2
1,3-Bisphosphoglycerate
3-Phospho-glycerate
Phosphoglycerate
kinase
ATP
ADP
2 - Phosphoglycerate
Phosphoglycerate mutase
Enolase
Phosphoenol Pyruvate
Pyruvate
Pyruvate kinase
CO2 + H20 (CAC)
Lactate dehydrogenaseLactate
Mg+2
H2O
ADP
ATP