Enzymes and transporters for carbohydrates digestion and absorption in the GI system along with their functional methods in cludibg glucose transporters and clinical correlates related to different carbohydrates metabolism like galactose and fructose and their hereditary intolerance of galactosemia, fructosuria and additional pathway of those carbohydrates like polyol pathway
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Lecture-1 on CHO Metabolism.pdf
1. Enzymes and Transporters
for Carbohydrates Digestion &
Absorption
Dr. Endriyas Kelta (DMD, MSc)
Assistant Professor, AAU
2. Carbohydrate Digestion
• More than 60 % of human diet is
carbohydrate
• Principal dietary carbohydrates of human:
– Plant polysaccharides: Starch & Cellulose
– Animal polysaccharide: Glycogen
– Disaccharides: Sucrose & Lactose
– Free monosaccharides: Glucose & Fructose
• All dietary carbohydrates are digested
mainly to Glucose, Galactose & Fructose
– Exception: Cellulose, which is not digested
2
3. Cont…
• Carbohydrate Digestion in the Mouth
– Digestion of starch & glycogen starts in the
mouth
• Salivary α-amylase
– Produced by cells in the back of mouth
– Works at optimum PH of 6.7
– Activated by Chloride ion
– Hydrolyzes α-(14)-glycosidic linkages of starch
and glycogen
– Major hydrolysis products:
» Small amounts of free glucose
» Large amounts of maltose and iso-maltose
» Large amounts of α-dextrins 3
4. Cont…
• Carbohydrate Digestion in the Stomach
– No enzyme in the stomach for carbohydrate
digestion
– However, action of salivary α-amylase continues
for about 20 minutes
– After 20 minutes, stomach HCl:
• Penetrates the food materials
• Deactivates the enzyme by lowering the PH optimum
– Due to HCl penetrations, the stomach contents
now become more acidic
4
5. Cont…
• Carbohydrate Digestion in the Small
Intestine
– Acidic stomach contents pass into small intestine
• Pancreatic α-amylase
– Produced by pancreas
– Works at optimum PH= 7.1
– Activated by chloride ion
– Supported by bicarbonate ions secreted from the
pancreas
» Raises PH to range of optimum pH for pancreatic
α-amylase
– Hydrolyzes α-(14)-glycosidic linkages b/n mono-
sugar residues
5
6. Cont…
– Major hydrolysis products:
• Large amounts
» Free Glucose
» Maltose
» Iso-maltose
» Tri-saccharide: Malto-triose
• Small amounts of α-dextrins
– Intestinal enzymes (Disaccharidases)
• Produced by intestinal mucosal cells localized to
intestinal brush borders
• Work at optimum PH of 6.1
• Supported by bicarbonate ions secreted from the
pancreas
– Reduces PH to range of optimum pH for intestinal
enzymes 6
7. Cont…
• Intestinal enzymes act up on:
– Major hydrolysis products of pancreatic α-amylase:
• Maltose
• Iso-maltose
• Malto-triose
• α-dextrins
– Dietary disaccharides:
• Sucrose
• Lactose
• Major hydrolysis products:
– Glucose
– Galactose
– Fructose
•Maltase (α-(14)-Glucosidase)
•Isomaltase (α-(16)-Glucosidase)
•Sucrase (Invertase)
•Lactase
7
9. Carbohydrate Absorption & Transportation
• Major hydrolysis products of intestinal
enzymes:
– Glucose
– Galactose
– Fructose
• Taken up into absorptive epithelial cells of small
intestine
– Protein-mediated:
» Na+-dependent active transport
» Facilitative diffusion
• Transported into blood
• Circulate to liver and peripheral tissues
– Protein-mediated facilitative diffusion 9
10. Cont…
• For active transport of mono-sugars:
– Structure Hexose ring
– -OH group at C-2 Right side
• Glucose & Galactose
– Taken up by protein mediated Na+-dependent
active transport
• Fructose & Glucose (sometimes)
– Taken up by protein mediated facilitative diffusion
• Facilitative diffusion of mono-sugars:
– Mediated by tissue-specific glucose transport
(GLUT) protein families
– Type of GLUT found in each cell reflects the
role of glucose metabolism in that cell
10
13. Fates of Mono-sugars after Absorption &
Transport into Liver & Peripheral Tissues
• Inside liver cells
– Galactose & Fructose Glucose & its
metabolites
• Hepatic glucose
– Catabolized (via glycolysis & pentose shunt)
– Stored in form of glycogen
– Channeled via systemic circulation to peripheral
tissues
• Peripheral Glucose
– Catabolized (via glycolysis & pentose shunt)
– Stored in form of glycogen or TAG 13
14. Fate of Galactose & Fructose
Metabolism of Galactose
– Derived from hydrolysis of “lactose” (sugar of
milk) in intestine by enzyme “lactase”
– Most of dietary galactose is converted to
glucose & goes to systemic circulation as glucose
• 1st : Phosphorylation of galactose at C-1
Galactose-1-P
– Catalyzed by galactokinase
– This reaction is irreversible & ATP used as
phosphoryl group donor
• 2nd : Galactose-1-P plus UDP-Glucose
UDP-galactose plus Glucose-1-P
– Catalyzed by Galactose-1-P-uridyl transferase14
15. Cont…
• 3rd : UDP-Galactose converted into UDP-
Glucose
– Catalyzed by UDP-Galactose epimerase
– This reaction is freely reversible
• 4th : UDP-glucose plus ppi Glucose 1-
phosphate plus UTP
– Reversible reaction
– Catalyzed by UDP-glucose pyrophosphorylase
• 5th: Glucose 1-phosphate converted into
glucose 6-phosphate by phosphoglucomutase
15
20. Cont…
Metabolism of Fructose
– Chief dietary source is sucrose taken as table
sugar (cane sugar)
– Sucrose is hydrolyzed in intestine to glucose &
fructose by Sucrase
– Most of dietary fructose is converted to glucose
& goes to systemic circulation as glucose
– Fructose can be utilized in two mechanisms:
• Phosphorylation by hexokinase
• Phosphorylation by fructokinase
20
21. Cont…
– Phosphorylation by hexokinase:
• Fructose phosphorylated at C-6 Fructose 6-
phosphate Entry into EM pathway
• This is irreversible reaction & ATP used as phosphoryl
group donor
21
22. Cont…
• Phosphorylation by fructokinase:
– Fructokinase:
» Present mainly in liver, muscle, kidney & intestine
» Phosphorylates fructose only at C-1 Fructose 1-
phosphate
» This reaction is irreversible & ATP is used as
phosphoryl group donor
» Its activity is not affected by insulin
» This is why fructose disappears from blood of
diabetic patients at a normal rate
22
23. Cont…
– Aldolase B reaction
• Catalyzes cleavage of Fructose 1-phosphate DHAP
(Entry EM pathway) & Glyceraldhyde
23
24. Cont…
– Fate of Glyceraldehyde:
• Can be Converted into
– GA3-P (Major & principal pathway)
» Triose kinase phosphorylates into GA3-P in
expense of ATP
– 2-Phosphoglycerate (2-PG)
– DHAP
24
27. Clinical Comments related to Fructose metabolism
• Hereditary Fructose Intolerance
– Congenital Aldolase-B deficiency Inability to convert
fructose to glucose in normal manner
– Excessive & prolonged rise of fructose & fructose-1-p in blood
– Manifestations:
• Hypoglycemia
– Reasons:
» Excessive insulin secretion
» Inhibition of phosphoglucomutase by fructose-1-P
• Cataract development
– Reasons:
» Excess of Fructose in lens reduced to “Sorbitol”
by Sorbitol dehydrogenase
• Soorbitol cannot escape from lens cells
• Osmotic effect of sugar alcohol contributes to
injury of lens proteins Development of
cataracts 27
28. Polyl-Pathway of Fructose Metabolism
– Fructose:
• Principal & major energy source for spermatozoa
• Formed from glucose in the seminal vesicle
– 1st, D-glucose is reduced to D-sorbitol by aldose
reductase
– Then, D-sorbitol oxidized to D-Fructose by
Sorbitol dehydrogenase
28
29. Carbohydrate digestion & absorption defects
• Lactose intolerance
– Congenital or acquired lactase deficiency
– Lactose is neither digested nor absorbed
• Directly passes into large intestinal lumen
– Results in the following conditions.
» Abdominal distension & cramp
• Bacteria in the large intestinal lumen ferment
lactose & produce CO2 gas
» Diarrhea & dehydration
• Lactose possess increased osmotic pressure
(holds more H2O)
• Monosaccharide mal-absorption
– Congenital Na+-dependent carrier protein defect
– Affects only glucose and galactose absorption
– Fructose absorption is not affected 29