Abosrption and metabolism of cho

33
Carbohydrates Carbohydrates By Khuram Aziz Senior Demonstrator Junior sci, by IBC Member of NAYS 1

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Transcript of Abosrption and metabolism of cho

Page 1: Abosrption and metabolism of cho

CarbohydratesCarbohydrates

By Khuram AzizSenior Demonstrator

Junior sci, by IBCMember of NAYS

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SF Biology II 2

Carbohydrate (CHO) DigestionCarbohydrate (CHO) DigestionIn lumenIn lumenStarch Starch maltose + maltriose + maltose + maltriose + αα-limit dextrins-limit dextrinsAmylaseAmylase

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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

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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

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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

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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

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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

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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

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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.

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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

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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.

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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

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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

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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

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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.

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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.

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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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

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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