1. Carbohydrate Metabolism
Dr. Deon Bennett

2. I. Introduction: More than 60% of our foods are carbohydrates.
Starch, glycogen, sucrose, lactose and cellulose are the chief carbohydrates in our food.
Before intestinal absorption, they are hydrolysed to hexose sugars (glucose, galactose and fructose).
A family of a glycosidases that degrade carbohydrate into their monohexose components catalyzes hydrolysis of glycosidic bonds.

3. Digestion of carbohydrate by salivary α -amylase (ptylin) in the mouth:
This enzyme is produced by salivary glands. Its optimum pH is 6.7.
Food remains for a short time in the mouth, digestion of starch and glycogen may be incomplete and gives a partial digestion products called: starch dextrins (amylodextrin, erythrodextrin and achrodextrin).
Therefore, digestion of starch and glycogen in the mouth gives maltose, isomaltose and starch dextrins.

4. Stomach: carbohydrate digestion stops temporarily due to the high acidity which inactivates the salivary - amylase.
Digestion of carbohydrate by the pancreatic - amylase small intestine in the small intestine.
A. α-amylase enzyme is produced by pancreas and acts in small intestine. Its optimum pH is 7.1.
B. It is also activated by chloride ions.
C. It acts on cooked and uncooked starch, hydrolysing them into maltose and isomaltose.
Final carbohydrate digestion by intestinal enzymes:
A. The final digestive processes occur at the small intestine and include the action of several disaccharidases. These enzymes are secreted through and remain associated with the brush border of the intestinal mucosal cells.

5. The disaccharidases include:
1. Lactase (β-galactosidase) which hydrolyses lactose into two molecules of glucose and galactose:
Lactase
Lactose Glucose + Galactose
2. Maltase ( α-glucosidase), which hydrolyses maltose into two molecules of glucose:
Maltase
Maltose Glucose + Glucose
3. Sucrose (α-fructofuranosidase), which hydrolyses sucrose into two molecules of glucose and fructose:
Sucrose
Sucrose Glucose + Fructose
4. α - dextrinase (oligo-1,6 glucosidase) which hydrolyze (1 ,6) linkage of isomaltose.
Dextrinase
Isomaltose Glucose + Glucose

6. Digestion of cellulose:
A. Cellulose contains β(1-4) bonds between glucose molecules.
B. In humans, there is no β (1-4) glucosidase that can digest
such bonds. So cellulose passes as such in stool.
C. Cellulose helps water retention during the passage of food
along the intestine  producing larger and softer feces 
preventing constipation.

7. Absorptions
The end products of carbohydrate digestion are monosaccharides: glucose, galactose and fructose.
They are absorbed from the jejunum to portal veins to the liver, where fructose and galactose are transformed into glucose.

8. Summary of types of functions of most important glucose transporters:
Site
Function
Intestine and renal tubules.
Absorption of glucose by active transport (energy is derived from Na+- K+ pump)
SGLT-1
Intestine and sperm
Fructose transport and to a lesser extent glucose and galactose.
GLUT -5
Intestine and renal tubule
-β cells of islets-liver
Transport glucose out of intestinal and renal
cells  circulation
GLUT - 2

9. Glucose Oxidation
major Pathway

10. Major pathways of glucose utilization

11. I. Glycolysis (Embden Meyerhof Pathway):
A. Definition:
1. Glycolysis means oxidation of glucose to give pyruvate (in the
presence of oxygen) or lactate (in the absence of oxygen).
B. Site:
cytoplasm of all tissue cells, but it is of physiological importance in:
1. Tissues with no mitochondria: mature RBCs, cornea and lens.
2. Tissues with few mitochondria: Testis, leucocytes, medulla of the
kidney, retina, skin and gastrointestinal tract.
3. Tissues undergo frequent oxygen lack: skeletal muscles especially
during exercise.

12. D. Energy (ATP) production of glycolysis:
C. Steps:
Stages of glycolysis
1. Stage one (the energy requiring stage):
a) One molecule of glucose is converted into two molecules of
glyceroaldhyde-3-phosphate.
b) These steps requires 2 molecules of ATP (energy loss)
2. Stage two (the energy producing stage(:
a) The 2 molecules of glyceroaldehyde-3-phosphate are converted into
pyruvate (aerobic glycolysis) or lactate (anaerobic glycolysis).
b) These steps produce ATP molecules (energy production).
D. Energy (ATP) production of glycolysis:
ATP production = ATP produced - ATP utilized

15. In the energy investment phase, ATP provides activation energy by phosphorylating glucose.
This requires 2 ATP per glucose.
In the energy payoff phase, ATP is produced by substrate-level phosphorylation and NAD+ is reduced to NADH.
2 ATP (net) and 2 NADH are produced per glucose.

16. Energy Investment Phase

17. Energy-Payoff Phase

18. Glucose  Pyruvate  Lactate
Importance of lactate production in anerobic glycolysis:
1. In absence of oxygen, lactate is the end product of glycolysis:
2. In absence of oxygen, NADH + H+ is not oxidized by the
respiratory chain.
3. The conversion of pyruvate to lactate is the mechanism for
regeneration of NAD+.
4. This helps continuity of glycolysis, as the generated NAD+ will be
used once more for oxidation of another glucose molecule.
Glucose  Pyruvate  Lactate

19. Differences between aerobic and anaerobic glycolysis:
Lactate
Pyruvate
1. End product
2 ATP
6 ATP
2 .energy
Through Lactate formation
Through respiration chain in mitochondria
3. Regeneration of NAD+
Not available as lactate is cytoplasmic substrate
Available and 2 Pyruvate can oxidize to give 30 ATP
4. Availability to TCA in mitochondria

20. Cori cycle
Refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is converted back to lactate.

21. Cori cycle

22. Three possible catabolic
fates of the pyruvate
formed in glycolysis 22

23. Special features of glycolysis in RBCs:
1. Mature RBCs contain no mitochondria, thus:
a) They depend only upon glycolysis for energy production
(=2 ATP).
b) Lactate is always the end product.
2. Glucose uptake by RBCs is independent on insulin hormone.
3. Reduction of met-hemoglobin: Glycolysis produces NADH +
H+, which used for reduction of met-hemoglobin in red cells.

24. Biological importance (functions) of glycolysis:
1. Energy production:
a) anaerobic glycolysis gives 2 ATP.
b) aerobic glycolysis gives 6 ATP.
2. Oxygenation of tissues:
Through formation of 2,3 bisphosphoglycerate, which decreases the
affinity of Hemoglobin to O2.
3. Provides important intermediates:
a) Dihydroxyacetone phosphate: can give glycerol-3phosphate, which is
used for synthesis of triacylglycerols and phospholipids (lipogenesis).
b) 3 Phosphoglycerate: which can be used for synthesis of amino acid
serine.
c) Pyruvate: which can be used in synthesis of amino acid alanine.
4. Aerobic glycolysis provides the mitochondria with pyruvate, which gives
acetyl CoA use in Krebs' cycle.

25. Reversibility of glycolysis (Gluconeoqenesis):
1. Reversible reaction means that the same enzyme can catalyzes the
reaction in both directions.
2. all reactions of glycolysis -except 3- are reversible.
3. The 3 irreversible reactions (those catalyzed by kinase enzymes) can
be reversed by using other enzymes.
Glucose-6-p  Glucose
F1, 6 Bisphosphate  Fructose-6-p
Pyruvate  Phosphoenol pyruvate
4. During fasting, glycolysis is reversed for synthesis of glucose from non- carbohydrate sources e.g. lactate. This mechanism is called:
gluconeogenesis.

26. Gluconeogenesis
Is largely a reversal of glycolysis except
For three irrevesible step in glycolysis
which must be bypassed

27. A carboxyl group is removed as CO2.
As pyruvate enters the mitochondrion, a multienzyme complex modifies pyruvate to acetyl CoA which enters the Krebs cycle in the matrix.
A carboxyl group is removed as CO2.
A pair of electrons is transferred from the remaining two-carbon fragment to NAD+ to form NADH.
The oxidized fragment, acetate, combines with coenzyme A to form acetyl CoA.
Fig. 9.10

28. The Citric Acid Cycle
Tricarboxylic Acid Cycle
TCA Cycle
Kreb’s Cycle

30. All of the enzymes of the TCA cycle
and the electron transport system are
in the mitochondria of animal cells

31. Oxidative Phosphorylation
Takes place in the mitochondria
The process by which ATP is formed as a result of transfer of electrons from NADH or FADH2 to O2.
Electron released in re-oxidation of NADH and FADH2 flow through a series of membrane proteins (referred to as electron transport chain).
This generates a proton gradient across the membrane.
The regulation of oxidative phosphorylation is governed primarily by the need for ATP.

32. Oxidation of extramitochondrial NADH + H+:
1. cytoplasmic NADH + H+ cannot penetrate mitochondrial membrane;
however, it can be used to produce energy (4 or 6 ATP) by respiratory
chain phosphorylation in the mitochondria.
2. This can be done by using special carriers for hydrogen of NADH + H+
These carriers are either dihydroxyacetone phosphate (Glycerophosphate
shuttle) or oxaloacetate (aspartate malate shuttle).
a) Glycerophosphate shuttle:
1) It is important in certain muscle and nerve cells.
2) The final energy produced is 4 ATP.
3) Mechanism:
- The coenzyme of cytoplasmic glycerol-3- phosphate dehydrogenase
is NAD+.
- The coenzyme of mitochodrial glycerol-3-phosphate dehydogenase is
FAD.
- Oxidation of FADH, in respiratory chain gives 2 ATP. As glycolysis
gives 2 cytoplasmic NADH + H+  2 mitochondrial FADH, 2 x 2
ATP  = 4 ATP.
b) Malate – aspartate shuttle:
1) It is important in other tissues patriculary liver and heart.
2) The final energy produced is 6 ATP.

36. The pentose phosphate pathway is an alternate route for the oxidation of glucose.

37. The pentose phosphate pathway has two main functions
Generation of NADPH
- mainly used for reductive syntheses of fatty acids, steroids, amino acids via glutamate dehydrogenase; and maintenance of reduced glutathione in erythrocytes and other cells.
- active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testes, and lactating mammary gland
- not active in non-lactating mammary gland and has low activity in skeletal muscle.
Production of ribose residues for nucleotide and nucleic acid synthesis.

38. Reactions of the pentose phosphate pathway occur in the cytosol in two phases
Oxidative non-reversible phase
Non-oxidative reversible phase
NADP+, not NAD +, is used as hydrogen acceptor
1st phase
- Glucose 6-phosphate undergoes dehydrogenation and decarboxylation to give a pentose, ribulose 5-phosphate, which is converted to its isomer, D-ribose 5-phosphate.
- Overall equation of 1st phase:
Glucose 6-phosphate + 2 NADP++ H2O
ribose 5-phosphate + CO2 + 2 NADPH + 2 H+

39. Oxidative reactions of the pentose phosphate pathway.
The end products are D-ribose 5-phosphate and NADPH

40. In tissues requiring primarily NADPH rather than ribose 5- phosphate, these pentose phosphates can be recycled into glucose 6- phosphate.
Overall, 6 five-carbon sugars are converted to 5 six-carbon sugars

41. General scheme of the pentose phosphate pathway of glucose oxidation

42. III. Defects of carbohydrate digestion and absorption:
A. Lactase deficiency = lactose intolerance:
1. Definition:
a) This is a deficiency of lactase enzyme which digest lactose into
glucose and galactose
b) It may be:
(i) Congenital: which occurs very soon after birth (rare).
(ii) Acquired: which occurs later on in life (common).
2. Effect: The presence of lactose in intestine causes:
a) Increased osmotic pressure: So water will be drawn from the tissue
(causing dehydration) into the large intestine (causing diarrhea).
b) Increased fermentation of lactose by bacteria: Intestinal bacteria
ferment lactose with subsequent production of CO2 gas. This causes
distention and abdominal cramps.
c) Treatment: Treatment of this disorder is simply by removing lactose
(milk) from diet.

43. IV. Fate of absorbed sugars:
B. Sucrase deficiency:
A rare condition , which typically occurs early in childhood.
C. Monosaccharide malabsorption:
This is a congenital condition in which glucose and galactose are absorbed
only slowly due to defect in the carrier mechanism. Because fructose is not
absorbed by the carrier system, its absorption is normal.
IV. Fate of absorbed sugars:
Monosaccharides (glucose, galactose and fructose) resulting from carbohydrate digestion are absorbed and undergo the following:
A. Uptake by tissues (liver):
After absorption the liver takes up sugars, where galactose and fructose are converted into glucose.
B. Glucose utilization by tissues:
Glucose may undergo one of the following fate:

44. 1. Oxidation: through
a) Major pathways (glycolysis and Krebs' cycle) for production of energy.
b) Hexose monophosphate pathway: for production of ribose, deoxyribose
and NADPH + H+
c) Uronic acid pathway, for production of glucuronic acid, which is used in
detoxication and enters in the formation of mucopolysaccharide.
2. Storage: in the form of:
a) Glycogen: glycogenesis.
b) Fat: lipogenesis.
3. Conversion: to substances of biological importance:
a) Ribose, deoxyribose  RNA and DNA.
b) Lactose  milk.
c) Glucosamine, galactosamine  mucopolysaccharides.
d) Glucoronic acid  mucopolysaccharides.
e) Fructose  in semen.

45. References
/ Lecturers/ Carbohydrate%20Metabolism.. Retrieved 15/10/12 .
Retrieved on 15/10/12
Lehninger Principles of Biochemistry 3rd Ed. pp
cronus.uwindsor.ca/units/biochem/.../Citric%20acid%20cycle.ppt retrived 17/10/12
Nelson, David L., & Cox, Michael M.(2005) Lehninger Principles of Biochemistry Fourth Edition. New York: W.H. Freeman and Company, p. 543.
Biochemistry by Lubert Stryer, Jeremy M. Berg and John L. Tymoczko (22 Mar 2002)
Lippincott's Illustrated Reviews: Biochemistry, International Student Edition (Lippincott's Illustrated Reviews Series) by Richard A. Harvey and Denise R. Ferrier and Pamela Champe (2005)