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Diegestion Absorption of CHO and Hexose sugar metabolism.pdf
1. Bihonegn Birhan (BSc. MSc.)
Instructor of Medical Biochemistry
Digestion,Absorption of Carbohydrates and Hexose Sugars
Metabolism
1
2. Digestion of carbohydrates
Dietary carbohydrates:
Polysaccharides: starch and glycogen
Disaccharides: sucrose (cane sugar),lactose (milk sugar) and maltose
Monosaccharides: fructose & pentoses
Liquid food materials: milk,soup,fruit juice
2
3. Digestion of carbohydrates (CHO)
CHO present in three forms:
Digestible
Ready-to-absorb
Non-digestible
• Cellulose, pentosans, hemicellulose, etc.
3
5. Digestion of carbohydrates
Digestion in mouth:
• Homogenization
• Mastication
• Dietary polysaccharides become hydrated
Salivary amylase (ptyalin)
Action of Ptyalin/Salivary Amylase/α-amylase:
Cl– ion for activation & optimum pH 6.7 (range 6.6 to 6.8)
Hydrolyzes α-1 → 4 internal glycosidic linkage.
Producing:
• -dextrins
• Maltose
• Maltotriose
Starch digestion is incomplete.
5
6. Digestion of carbohydrates
Digestion in stomach
Salivary amylase stops its action in stomach when pH falls.
Acidic pH 1 – 2
Digestion in the Small Intestine
Two enzymes that digest CHO:
1.Pancreatic juice
2.Intestinal mucosal brush border enzymes
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7. Digestion of carbohydrates
Digestion in duodenum:
Pancreatic juice
Pancreatic amylase (also called amylopsin)
• α –amylase:
• Optimum PH 7.1
• Cl– for activity
• Hydrolyses α-1→4 glycosidic linkage
Products of hydrolysis of starch/Glycogen:
Maltose
Maltotriose
-Limit dextrin (oligosaccharides with -1,6 branches )
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8. Digestion of carbohydrates
2. Intestinal mucosal brush border enzymes
Intestinal amylase:
Hydrolyses terminal α-1→4 glycosidic linkage.
Polysaccharides and oligosaccharides →free glucose molecules
Glucoamylase:
An exoglycosidase
Substrates :amylose,amylopectin,glycogen and maltose
Hydrolyzes -1,4 glycosidic bonds b/n glucosyl units,beginning at nonreducing end.
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9. Digestion of carbohydrates
2. Intestinal mucosal brush border enzymes ……
• Isomaltase–maltase
Hydrolyzes -1, 6 bonds in limit dextrins & -1,4 bonds in maltose and
maltotriose.
α-limit dextrin → maltose+ glucose
• Sucrase–maltase
Hydrolyzes sucrose, maltose, and maltotriose
9
11. Dietary fibers
-1,4 glucosidic linkage of Cellulose
not hydrolyzed by human digestive enzymes
Hemicellulose, lignin, gums, pectins & pentosans
Are also indigestible
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13. Dietary…(Cont’d)
Dietary fibers passes as it is in stools & beneficial for:
Increasing bulk of intestinal contents by adsorbing water
Stimulates peristaltic movements
to reduce stool transit time and prevents constipation
Lower contact with fecal mutagens.
High-fiber diets are also beneficial by reducing the incidence of:
Cancer of the colon
Cardiovascular disease
Diabetes mellitus
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14. Dietary … (Cont’d)
It induces establishment of normal colon bacteria
With several benefits including:
Fermentation of fibers
Production of vitamins Vitamin K & Biotin
However,excessive dietary fibers,
Fiber can bind minerals such as calcium,magnesium,iron and zinc,which limits their
absorption
E.g., Chelate calcium in an insoluble form
14
15. ABSORPTION OF CARBOHYDRATES
All monosaccharides completely absorbed in small intestine.
Two mechanisms of monosaccharides are suggested:
1. Simple diffusion:
Sugar concentration gradients between the intestinal lumen,mucosal cells and blood plasma.
All the monosaccharides are probably absorbed to some extent by simple‘passive’diffusion.
2.“Active”Transport Mechanisms
Glucose and galactose are absorbed actively very rapidly.
Fructose absorption is also rapid but < glucose & galactose
• But it is faster than pentoses.
Hence fructose may be absorbed by both simple diffusion & facilitated transport.
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16. Absorption of Carbohydrates
Absorption by the Intestinal Epithelium
Glc is transported through the absorptive cells of the intestine by:
Na-dependent facilitated transport
Facilitated diffusion
It enters the absorptive cells by binding to transport proteins.
2 types of Glc transport proteins are present in the intestinal cells:
Na+-dependent glucose transporters sGLT
Facilitative glucose transporters GLUT
16
17. Na+-Dependent Glucose Transporters
sGLT1 & sGLT2:
Located on the luminal side of the absorptive cells.
A low intracellular Na+ concentration is maintained by:
Na+,K+-ATPase on the serosal (blood) side of the cell.
uses the energy from ATP cleavage to pump Na+ out of the cell.
Transport of Glc from a low conc. in the lumen to a high conc. in the cell is by
• Cotransport of Na+
• Secondary active transport
Active transport of sugars are inhibited by:
Strophanthin,Ouabain, Dinitrophenol (DNP), Phloridzin
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19. Facilitative GlucoseTransporters
GLUT-1 to GLUT-12:
Which do not bind Na+ & are located on the serosal side
Glucose moves via the facilitative transporters:
from the high conc. inside the cell to the lower conc. in the blood
Facilitative transporters for Glc also exist on the luminal side.
• GLUT-5
19
21. Facilitative transport
By transport proteins
Multiple groups on the protein
bind the -OH groups of Glc &
close behind it as it is released into the cell
i.e.,the transporter acts like
“gated pore”
O = outside
I = inside
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22. Galactose & Fructose Absorption
Through GlucoseTransporters
Galactose:
Absorbed through the same mechanisms as glucose
It enters the absorptive cells on the luminal side via:
• Na+-dependent glucose transporters &
Transported through the serosal side by:
• Facilitative glucose transporters
Fructose:
Both enters & leaves absorptive epithelial cells by:
• Facilitated diffusion GLUT-5
22
23. Transport of Monosaccharides intoTissues
Properties of the GLUT transport proteins differ b/n tissues
Reflecting the function of glucose metabolism in each tissue
In most cell types, the rate of Glc transport across the membrane is
Not rate-limiting for glucose metabolism
b/c the isoform of transporter present in these cell types:
has a relatively low Km for Glc, or
is present in relatively high conc. in the cell membrane
so that the IC Glc conc. reflects that in the blood
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24. Transport of …(Cont’d)
However, in several tissues, the rate of transport becomes rate limiting when:
Serum level of Glc is low, or
Low levels of insulin signal the absence of dietary Glc.
Liver: GLUT-2
Km for the glucose transporter is relatively high compared with that of other
tissues.
15 mM or above
This is in keeping with the liver’s role as the organ that maintains blood
glucose levels.
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25. Transport of …(Cont’d)
Muscle & Adipose tissue: GLUT-4
Transport of Glc is greatly stimulated by insulin.
The mechanism involves recruitment of GLUT-4
In adipose tissue:
es Glc availability for the synthesis of Fatty acids & Glycerol
In skeletal muscle es Glc availability for:
• Glycolysis
• Glycogen synthesis
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27. Defects in digestion and absorption of carbohydrates (including inherited disorders)
Lactase Deficiency
Intolerance to lactose
Diarrhea
Flatulence
Abdominal cramps
Distension
Treatment: reduce the consumption of milk, taking lactase in pills form
prior to eating, taking lactase treated food.
Cows’ milk allergy is much more common than lactose intolerance in babies
It is caused by an allergic reaction of the baby’s immune system to proteins in the milk.
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28. 28
Cows’ milk allergy is much more common than lactose intolerance in babies and is caused
(not by lactose) by an allergic reaction of the baby’s immune system to proteins in the milk.
29. Sucrase Deficiency
Inherited deficiency of sucrase and isomaltase
Symptoms in early childhood (sucrose: cane sugar and table sugar)
Disacchariduria:
Disaccharidase deficiency—Excretion of disaccharides
Intestinal damage (e.G. Sprue and celiac disease)
~300 mg or more of disaccharides may be excreted
Monosaccharide Malabsorption
Due to inherited disorders of carrier protein.
• Necessary for absorption of glucose and /galactose
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35. Glycolysis
IC Site &Tissue Distribution
It occurs in the cell cytosol of all tissues of the body.
RBCs
Cornea, lens and some parts of retina
Kidney (medulla), testicles, leukocytes and white muscle fibers
Contracting muscles
• occlusion of blood vessels by the muscular contraction
Cancer cells
Brain & gastrointestinal tract
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36. Enzymes involved and the Kinds of Reactions in Glycolysis
Enzymes: (cytosol, Mg2+)
Kinds of Reactions in Glycolysis:
Phosphoryl transfer
Phosphoryl shift
Isomerization
Dehydration
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39. Payoff phase of glycolysis
39
Fluoride
Arsenite,Iodoacetate & Iodoacetamide
40. Figure - Pathway for biosynthesis and degradation of 2,3-BPG
Special features of glycolysis in RBCs (Rapoport-Lubering cycle)
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41. Glycolysis
The total inputs and the outputs of all the 10 glycolytic reactions may be written
as follows :
Glucose + 2 ATP + 2 Pi + 2 NAD+ + 2 H+ + 4 ADP→ 2 pyruvate + 2 H+ + 4 ATP +
2 H2O + 2 NADH + 2 H+ + 2ADP
Net equation for the transformation of glucose into pyruvate :
Glucose + 2 Pi + 2 ADP + 2 NAD → 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
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42. Glycolysis
Step Reaction
Consumption
of ATP
Gain of ATP
1
3
7
10
Glucose→ Glucose 6-phosphate
Fructose 6-phosphate → Fructose 1, 6-diphosphate
1, 3-diphosphoglycerate → 3-phosphoglycerate
Phosphoenolpyruvate → Pyruvate
1
1 × 2 = 2
1 × 2 = 2
2 4
Net gain of ATP = 4 – 2 = 2
Table Energy yield of glycolysis
1
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44. Muscle anaerobic glycolysis (lactic fermentation)
The net equation for anaerobic glycolysis in muscles and lactate fermentation in some
microbes would then be :
Glucose + 2 Pi + 2 ADP → 2 lactate + 2 ATP + 2 H+ + 2 H2O
No net oxidation or reduction.
Lactate dehydrogenase
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45. Cori cycle
Lactate is taken up by other tissues (liver,
heart, and skeletal muscle) and oxidized
back to pyruvate.
In the liver, the pyruvate serves as a
precursor for gluconeogenesis.
The cycling of lactate and glucose between
peripheral tissues (RBC & skeletal
muscle) and liver is Cori cycle
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46. ALCOHOLIC FERMENTATION
In yeast and other microorganisms
The net equation for alcoholic fermentation would then be:
Glucose + 2 Pi + 2 ADP → 2 Ethanol + 2 CO2 + 2ATP + 2 H2O
No net oxidation-reduction.
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47. Biomedical Importances of glycolysis
Energy (ATP) source for skeletal muscle even in absence of O2.
Haemolytic anaemias: Inherited enzyme deficiencies:
Hexokinase deficiency and pyruvate kinase deficiency
Role in cancer therapy:
In fast-growing cancer cells, rate of glycolysis is very high.
o ↑more pyruvate → ↑lactic acid (local lactic acidosis).
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48. Fig.The anaerobic metabolism of glucose in tumor cells
Tumors of nearly all types carry out
glycolysis at a much higher rate than
normal tissue, even when oxygen is
available.“Warburg effect”
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51. Entry of dietary glycogen,starch,disaccharides,and hexoses into the preparatory stage of glycolysis
• Glucose is the center of carbohydrate metabolism.
• Other sugars in the diet are converted to
intermediates of glucose metabolism,when
carbohydrates other than glucose are required.
53. Fructose metabolism
Liver, small intestinal mucosa & kidney (fructokinase & aldolase B)
Two pathways for the metabolism of fructose:
1. In muscle & adipose tissue, Fru → Fru 6-P (hexokinase)
2. In liver, kidney & SI mucosa, Fru → Fru 1-P (fructokinase/ketohexokinase)
o Aldolase isoforms (A, B, C, & fetal aldolases)
• Aldolase B (liver,kidney & SI mucosa)
• AldolaseA → muscle & most other tissues
• Aldolase C → brain
• Fetal aldolase → liver before birth
• All can cleave Fru1,6-BP
• But Only aldolase B can also cleave Fru-1-P
54. The rate of fructose metabolism is more rapid than that
of glucose because the trioses formed from fructose 1-
phosphate bypass phosphofructokinase-1—the major
rate-limiting step in glycolysis.
Fructose metabolism
57. Polyol Pathway and Fructose metabolism
The effect of hyperglycemia on sorbitol metabolism and diabetic cataract formation.
Insulin is not required for the entry of glucose into:
• Lens
• Retina
• Schwann cells of peripheral nerves
• Liver
• Kidney
• Placenta
• Red blood cells
• Cells of the ovaries
• Seminal vesicles
58. Polyol Pathway and Fructose metabolism
In uncontrolled diabetes,large amounts of glucose may enter into the above cells
during times of hyperglycemia.
Elevated intracellular [glucose] and an adequate supply of NADPH:
Cause aldose reductase to produce a significant increased amount of sorbitol and trapped inside
the cell
It can be oxidized into fructose by sorbitol dehydrogenase
But when sorbitol dehydrogenase is low or absent in lens,retina,kidney,and nerve cells,sorbitol
accumulates in these cells.
• High osmotic pressure is created in these cells.
• Cataract formation,retinopathy,nephropathy and neuropathy
Sorbitol accumulation can be prevented by aldose reductase inhibitors in experimental
animals.
But no current evidence available that inhibitors are effective in preventing cataract or
diabetic neuropathy in humans.
59. Disorders of Fructose metabolism
1. A benign condition caused by fructokinase deficiency (essential fructosuria)
2. A severe disturbance of liver and kidney metabolism
Caused by aldolase B deficiency (hereditary fructose intolerance,HFI)
The first symptoms of HFI appear when a baby is weaned from milk and begins to
eat food containing sucrose or fructose.
60. Disorders of Fructose metabolism
Hereditary fructose intolerance,HFI
Fructose 1-phosphate accumulates:
Vomiting
Hepatomegaly →hepatic failure
Jaundice
Pi,ATP,inhibition of biosynthetic pathway
AMP Hyperuricemia
blood clotting factors →hemorrhage
Hypoglycemia & lactic acidosis
Diagnosis of HFI by examining fructose in the urine,enzyme assay or by DNA-based testing.
With HFI,sucrose and sorbitol & fructose must be removed from the diet to prevent liver failure and possible
death.
