1. CARBOHYDRATE METABOLISM
Mia Kusmiati
Departemen Biokimia FK UNISBA

3. Carbohydrates
Carbohydrates are called carbohydrates because they are essentially hydrates of carbon (i.e. they are composed of carbon and water and have a composition of (CH2O)n.
The major nutritional role of carbohydrates is to provide energy and digestible carbohydrates provide 4 kilocalories per gram. No single carbohydrate is essential, but carbohydrates do participate in many required functions in the body.

5. Carbohydrate Metabolism

8. Glucose transport

9. Glycolysis What is glycolysis?  Ten step metabolic pathway to
convert glucose into two molecules
of pyruvate and two molecules
each of NADH and ATP.
 All carbohydrates to be catabolized
must enter the glycolytic pathway.
- Glycolysis is central in generating
both energy and metabolic
intermediaries.

10. The Glycolysis Pathway
Major anaerobic pathway in all cells
NAD+ is the major oxidant
Requires PO4
Generates 2 ATP’s per glucose oxidized
End product is lactate (mammals) or ethanol (yeast)
Connects with Krebs cycle via pyruvate

11. Phase I. Energy Investment. Enzymes = hexokinase or glucokinase
1- Glucose is phosphorylated. Glucose enters a cell through a specific glucose transport process. It is quickly phosphorylated at the expense of an ATP. The investment of an ATP here is called “priming.”
Enzymes = hexokinase or
glucokinase
2. Isomerization of glucose 6-phosphate
Enzyme = phosphoglucoisomerase

12. glucose 6-phosphate fructose 6-phosphate
aldose to ketose isomerization reversible, G= 1.7 kJ/mole

13. Enzyme = phosphofructokinase
3- Second phosphorylation
Enzyme = phosphofructokinase
ATP ADP
fructose 1,6 bisphosphate
second ATP investment
highly exergonic, essentially
irreversible, G°´= kJ/mole
- highly regulated, modulating carbon
flux through glycolysis in response
to energy and carbon requirements

14. 4- Cleavage to two triose phosphates Enzyme = aldolase
HC=O H2COP
HCOH O=C
HCOP CH2OH H
glyceraldehyde dihydroxyacetone
3-phosphate phosphate
where P = phosphate
 cleaves a 6C sugar to 2 3C sugars
 G°´= kJ/mole, driven by next Rx.

15. 5-Isomerization of Dihydroxyacetone phosphate
Enzyme = triose-phosphate isomerase
H2C-OH
C=O
CH2-O- P
dihydroxyacetone glyceraldehyde
phosphate phosphate

16. 5-Isomerization of Dihydroxyacetone phosphate
Enzyme = triose-phosphate isomerase
H2C-OH
C=O
CH2-O- P
dihydroxyacetone glyceraldehyde
phosphate phosphate

17. only glyceraldehyde 3-phosphate can be used further in glycolysis.
 allows interconversion of two triose phosphate products
of aldolase cleavage
only glyceraldehyde 3-phosphate can be used further
in glycolysis.
 aldose-ketose isomerization similar
to phosphoglucoisomerase rxn
allows dihydroxyacetone phosphate to be metabolized
as glyceraldehyde 3-phosphate
reversible,G°´= +7.5 kJ/mole.
This is important in gluconeogenesis

18. Second Phase: End of First Phase:  Production of two glyceraldehyde
****************************************
End of First Phase:
 Production of two glyceraldehyde
3-phosphate molecules from one
glucose molecule with the
expenditure of two ATPs.
 Therefore: the energy yields of the
following steps are multipled by two.
*****************************************
Second Phase:

19. + 6- Oxidation of glyceraldehyde 3-phosphate
Enzyme= glyceraldehyde-3-phosphate
dehydrogenase O
HOPO
OH NAD NADH O
OPOH C=O
O HCOH
H2C
O- P +
glyceraldehyde 3-phosphate ,3 bisphosphoglycerate
-addition of phosphate, oxidation,
production of NADH, formation of
high energy compound

20. - first substrate level phosphorylation, yielding ATP
7- Transfer of phosphate to make ATP
Enzyme = phosphoglycerate kinase
O=C-O- P O=C-OH P
HC-OH + P HC-OH P
H2C-O-P P H2C-O-P P
Adenosine Adenosine
1,3PG ADP phosphoglycerate ATP
- first substrate level phosphorylation,
yielding ATP
- 2 1,3 bis PG yield 2 ATPs, thus so far
ATP yield = ATP input
- high free energy yield, G°´= -18.8kJ/mole drives several of the previous steps.

21. 8- Phosphate shift setup Enzyme= phosphoglycerate mutase
- shifts phosphate from position 3 to 2
- reversible, ΔG = kJ/mole

22. 9- Generation of second very high energy compound Enzyme = enolase
-- little energy change in this reaction,
ΔG = +1.7 kJ/mole because the
energy is locked into enolphosphate

23. phosphoenolpyruvate pyruvate second substrate level phosphorylation
10- Final generation of ATP
Enzyme = pyruvate kinase P
O H ADP ATP O
-OOC-C=CH OOC-C-CH3
phosphoenolpyruvate pyruvate
second substrate level phosphorylation
yielding ATP
- highly exergonic reaction,
irreversible, ΔG = kJ/mole.

28. Regulation of Glycolysis
6-phosphofructokinase-1
Allosteric enzyme
negative allosteric effectors
Citrate , ATP
Positive allosteric effectors
AMP, fructose1,6-bisphosphate, fructose2,6- bisphosphate
Changes in energy state of the cell (ATP and AMP)

29. Regulation of Glycolysis fig.6-4

30. Regulation of Glycolysis
Pyruvate Kinase
Allosteric enzyme
Inhibited by ATP.
Isoenzyme in liver
activated by fructose 1,6 bisphosphate
inhibited by alanine
Regulated by phosphorylation and dephosphorylation
Hexokinase
Different isoenzymes
Hexokinase IV
glucose 6-phosphate is an allosteric inhibitor
promote biosynthesis

32. The Significance of Glycolysis
Glycolysis is the emergency energy-yielding pathway
Main way to produce ATP in some tissues
red blood cells, retina, testis, skin, medulla of kidney
In clinical practice

33. Aerobic Oxidation of Glucose
Glucose oxidation
Oxidation of glucose to pyruvate in cytosol
Oxidation of pyruvate to acetylCoA in mitochondria
Tricarboxylic acid cycle and oxidative phosphorylation