1. Digestion and absorption of carbohydrate
Lecture no 1
Carbohydrate metabolism

2. We eat, we digest, we absorb, then what?
Three fates for nutrients
Most are used to supply energy for life
Some are used to synthesize structural or functional molecules
The rest are stored for future use

3. Carbohydrates in the food
Monosaccharides
Glucose
Found in fruits, vegetables, honey
“blood sugar” – used for energy
Fructose
“fruit sugar”
Found in fruits, honey
Galactose
Found as part of lactose in milk

4. Disaccharides Disaccharides – two linked sugar units
Sucrose: glucose + fructose
“table sugar”
Made from sugar cane and sugar beets
Lactose: glucose + galactose
“milk sugar”
Found in milk and dairy products
Maltose: glucose + glucose
Found in cereal grains
Product of starch breakdown

5. Galactose does not occur in foods singly but only as part of lactose.
fructose
glucose
galactose
sucrose
maltose
lactose
FIGURE 4-2: HOW MONOSACCHARIDES JOIN TO FORM DISACCHARIDES.
(fructose-glucose)
(glucose-glucose)
(glucose-galactose)
Galactose does not occur in foods singly but only as part of lactose.
Fig. 4-2a, p. 101

6. Complex Carbohydrates
Starch
Long chains of glucose units
Amylose – straight chains
Amylopectin – branched chains
Found in grains, vegetables, legumes
Glycogen
-- Highly branched chains of glucose units
Body’s storage form of carbohydrate
Made by animals
in muscle and liver
Amylopectin

7. Dietary Fiber Indigestible chains of monosaccharides
Found in fruits, vegetables, grains, ……

8. Carbohydrate Digestion and Absorption
Mouth
Salivary amylase begins digestion of starch into maltose
Small intestine
Pancreatic amylase completes starch digestion
Brush border enzymes digest the disaccharides
maltase, sucrase, lactase
End products of carbohydrate digestion
Glucose, fructose, galactose
Absorbed into bloodstream
Fiber not digested, excreted in feces

9. Carbohydrate Metabolism
General
80% of carbohydrates ingested contain glucose; remainder: fructose, galactose, ….
glucose is the body's preferred carbohydrate energy source
Metabolism of carbohydrates
Glycolysis
Citric acid cycle
Pentose Phosphate Pathway
Glycogen metabolism
Gluconeogenesis
Control of blood glucose level

10. Glycolysis From glucose to pyruvate
Anaerobic metabolism of glucose
From glucose to pyruvate

11. Glycolysis takes place in the cytosol of cells
10 steps from glucose to pyruvate
No need for oxygen
Produce pyruvate, ATP and NADH.

12. Pathway of glycolysis

13. Glycolysis Overview. Three stages. Investment stage :
Glucose to glucose-6-phosphate to
fructose-1,6-bisphosphate.
2 ATPs required.
Splitting stage.
F-1,6-BP to two triose phosphate.
Yield stage:
Triose phosphate to pyruvate
4 ATPs and 2 NADHs are produced.
4 ATPs – 2 ATPs = 2 ATPs net.

14. 1. Hexokinase catalyzes:
Glucose + ATP  glucose-6-P + ADP
A phosphoanhydride bond of ATP (~P) is cleaved.

15. 2. Phosphohexose Isomerase catalyzes:
glucose-6-P (aldose)  fructose-6-P (ketose)

16. 3. Phosphofructokinase-1 catalyzes:
fructose-6-P + ATP  fructose-1,6-bisP + ADP
This is the rate-limiting step of Glycolysis!

17. 4. Aldolase catalyzes:
fructose-1,6-bisphosphate  dihydroxyacetone-P + glyceraldehyde-3-P
The reaction is an aldol cleavage, the reverse of an aldol condensation.

18. 5. Triose Phosphate Isomerase (TIM) catalyzes:
dihydroxyacetone-P  glyceraldehyde-3-P
Glycolysis continues from glyceraldehyde-3-P.

19. 6. Glyceraldehyde-3-phosphate Dehydrogenase catalyzes:
glyceraldehyde-3-P + NAD+ + Pi 
1,3-bisphosphoglycerate + NADH + H+
This is the only step in Glycolysis in which NAD+ is reduced to NADH.

20. 7. Phosphoglycerate Kinase catalyzes:
1,3-bisphosphoglycerate + ADP  3-phosphoglycerate + ATP
One ATP is synthesized in this step

21. 8. Phosphoglycerate Mutase catalyzes:
3-phosphoglycerate  2-phosphoglycerate
Phosphate is shifted from the OH on C3 to the OH on C2.

22. 2-phosphoglycerate  phosphoenolpyruvate + H2O
9. Enolase catalyzes:
2-phosphoglycerate  phosphoenolpyruvate + H2O
NaF can inhibits activity of enolase

23. 10. Pyruvate Kinase catalyzes:
phosphoenolpyruvate + ADP  pyruvate + ATP
One ATP is synthesized in this step
Removal of Pi from PEP yields an unstable enol, which spontaneously converts to the keto form of pyruvate.

24. X2 X2

25. Glycolysis Balance sheet for ATP: How many ATP expended? ________
How many ATP produced? (Remember there are two 3C fragments from glucose.) ________
Net production of ATP per glucose: ________ 2 4 2

26. What happened for 2 pyruvates?
Basically three options depending on the environmental conditions

27. In animal tissues under anaerobic conditions
Reoxidize NADH to NAD+ that is needed for glycolysis;
Lactate, end-product of fermentation, serves as a form of nutrient
energy
Cell membranes contain carrier proteins that facilitate transport of
lactate.

28. Skeletal muscles ferment glucose to lactate during exercise, when the exercise is brief and intense.
Lactate released to the blood may be taken up by other tissues, or by skeletal muscle after exercise, and converted via Lactate Dehydrogenase back to pyruvate, which may be oxidized in Citric Acid Cycle or (in liver) converted to back to glucose via gluconeogenesis
Lactate serves as a fuel source for cardiac muscle as well as brain neurons.

29. Fermentation in yeast
Some anaerobic organisms metabolize pyruvate to ethanol. NADH is converted to NAD+ in the reaction catalyzed by Alcohol Dehydrogenase.

30. Regulation of Glycolysis
In 3 irreversible steps
In 3 important enzymes
hexokinase/glucokinase; phosphofructokinase-1; pyruvate kinase
PFK-1 is rate limiting enzyme and primary site of regulation.

31. Hexokinase Inhibited by product glucose-6-phosphate:
by competition at the active site
by allosteric interaction at a separate enzyme site.
Cells trap glucose by phosphorylating it, preventing exit
through glucose carriers.

32. --a variant of hexokinase found in liver.
Glucokinase
--a variant of hexokinase found in liver.
Glucokinase has a higher KM for glucose. It is active only at high [glucose].
Glucokinase is not subject to product inhibition by glucose-6-phosphate. Liver will take up & phosphorylate glucose even when liver [glucose-6-phosphate] is high.

33. Phosphofructokinase-1 (PFK-1)
The rate-limiting step of the Glycolysis pathway
Inducible enzyme
Induced in feeding by insulin
Repressed in starvation by glucagon
Allosteric regulation
Activated by AMP
Inhibited by ATP and Citrate
Activated by Fructose-2,6-bisphosphate

34. Pyruvate Kinase
Activated by fructose-1,6-biphosphate
Inhibited by ATP

35. Glycolysis is important for erythrocytes
Simplest cell in body.
No subcellular organelles.
No DNA-RNA-protein synthesis.
No mitochondria—no oxidative phosphorylation
Relies exclusively on glucose as fuel.
Glucose derived from blood.
Yields ATP from glycolysis.
End product is lactate.

36. 2,3-bisphosphoglycerate pathway in RBC

37. 2,3-Bisphosphoglycerate (2,3-BPG) is present in human red blood cells at approximately 5 mmol/L.
It binds with greater affinity to deoxygenated hemoglobin (e.g. when the red cell is near respiring tissue) than it does to oxygenated hemoglobin (e.g. in the lungs).
In bonding to partially deoxygenated hemoglobin it upregulates the release of the remaining oxygen molecules bound to the hemoglobin, thus enhancing the ability of RBCs to release oxygen near tissues that need it most.