Carbohydrate metabolism

This explains the metabolism of different carbohydrates, by Dr. Nandutu Agnes Makerere university

1. Carbohydrate metabolism
By Dr. Nandutu Agnes Masawi

2. Metabolism
•The sum of the chemical changes that
convert nutrients into energy and the
chemically complex products of cells
•Hundreds of enzyme reactions organized
into discrete pathways
•Substrates are transformed to products
via many specific intermediates
•Metabolic maps portray the reactions
•Intermediary metabolism

3. Metabolism
•Metabolism consists of catabolism
and anabolism
•Catabolism: degradative pathways
–Usually energy-yielding!
•Anabolism: biosynthetic pathways
–energy-requiring!

4. Catabolism and Anabolism
•Catabolic pathways converge to a
few end products
•Anabolic pathways diverge to
synthesize many biomolecules
•Some pathways serve both in
catabolism and anabolism

5. Carbohydrate Metabolism
•It denotes various biochemical processes
responsible for the formation, breakdown and
interconversion of carbohydrates in living
organisms
•Carbohydrate catabolism
• is divided into three stages
•Stage I Digestion of macromolecules
•Stage II conversion of monomers into a form that
can be completely oxidized to (Acetyl COA)
•Stage III complete oxidation and production of ATP

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7. Glycolysis cont’d
•For certain cells in the brain and eye, glycolysis is
the major ATP generating pathway
•Essentially all cells carry out glycolysis
•Ten reactions - same in all cells - but rates differ
•Two phases:
–First phase converts glucose to two G-3-P
–Second phase produces two pyruvates
•Products are pyruvate, ATP and NADH
•Three possible fates for pyruvate

8. Hexose Kinase
•1st step in glycolysis; DG large, negative
•This is a priming reaction - ATP is consumed
here in order to get more later
•ATP makes the phosphorylation of glucose
spontaneous

9. Rx 2: Phosphoglucoisomerase
•Uses open chain structure as substrate
•Near-equilibrium rxn (reversible)
•Enzyme is highly stereospecific (doesn’t
work with epimers of glucose-6-phosphate

10. Rx 3: Phosphofructokinase
PFK is the committed step in glycolysis!
•The second priming reaction of glycolysis
•Committed step and large, -DG – means PFK is
highly regulated
• b-D-fructose-6-phosphate is substrate for rxn

11. Phosphofructokinase is highly regulated
•ATP inhibits, AMP reverses inhibition
•Citrate is also an allosteric inhibitor
•Fructose-2,6-bisphosphate is allosteric
activator
•PFK increases activity when energy
status is low
•PFK decreases activity when energy
status is high

12. Rx 4: Aldolase
•Hexose cleaved to form two trioses
•C1 thru C3 of F1,6-BP -> DHAP
•C4 thru C6 -> G-3-P
•Near-equilibrium rxn
•Position of carbonyl group determines which
bond cleaved.
•If Glucose-6 –P was the substrate would end up
with 2 carbon and 4 carbon product

13. Rx 5: Triose Phosphate Isomerase (TPI)
C
1
C
2
O
C
3
C
4
C
5
C
6H
2OH
H OH
HO H
H OH
H OH
H
C
1H
2OPO
3
-2
C
2
C
3
C
4
C
5
C
6H
2OPO
3
-2
O
HO H
H OH
H OH
DHAP
C
1H
2OPO
3
-2
C
2
C
3
O
HO H
C
4
C
5
C
6H
2OPO
3
-2
H O
H OH
TPI
C
3
C
2
C
1H
2OPO
3
-2
H O
H OH
D-glucose F 1,6-BP
Aldolase
G-3-P
G-3-P

14. Rx 6: Glyceraldehyde-3P-Dehydrogenase
•G3P is oxidized and phosphorylated to 1,3-BPG
•Pi is used as phosphate donor
•C1 phosphoryl group has high group transfer
potential, used to phosphorylate ADP to ATP in next
step of glycolysis
•Arsenate can replace phosphate in rxn (results in
lower ATP)
•NADH generated in this reaction is reoxidized by
respiratory electron transport chain (generates ATP)

15. Rx 7: Phosphoglycerate Kinase (PGK)
•ATP synthesis from a high-energy phosphate
•This is referred to as "substrate-level
phosphorylation"

16. Rx 8: Phosphoglycerate
Mutase
•Phosphoryl group moves from C-3 to C-2
•Mutases are isomerases that transfer
phosphates from one hydroxyl to another
•Involves phosphate-histidine intermediate

17. Rx 9: Enolase
•"Energy content" of 2-PG and PEP are similar
•Enolase just rearranges to a form from which more
energy can be released in hydrolysis
•Requires Mg
2+
for activity,

18. Rx 10: Pyruvate Kinase
•Substrate level phosphorylation
generates second ATP
•Allosterically activated by AMP, F-1,6-
bisP
•Allosterically inhibited by ATP and
acetyl-CoA

19. Pyruvate can go in three major
directions after glycolysis
•Under aerobic conditions pyruvate is oxidized to
Acetyl-CoA which can enter Citric acid (TCA)
cycle.
•Under anaerobic conditions pyruvate can be
reduced to ethanol (fermentation) or lactate
•Under anaerobic conditions formation of ethanol
and lactate is important in the oxidization
NADH back to NAD
+

•Under aerobic conditions NADH is oxidized to
NAD
+
by the respiratory electron transport
chain.

20. Lactate formation
 
 
•In animals under anaerobic conditions pyruvate
is converted to lactate by the enzyme lactate
dehydrogenase
•Impt for the regeneration of NAD+ under
anaerobic conditions.
H
3C CC
O
O
O
NADH NAD
NADH
NAD
H
3C C
H
C
OH
O
O

21. • The circulatory
systems of large animals
are not efficient enough
O
2
transport to sustain
long periods of muscular
activity.
•Anaerobic conditions
lead to lactacte
accumulation and
depletion of glycogen
stores
•Short period of intense
activity must be followed
by recovery period
•Lactic acidosis causes
blood pH to drop
Cori Cycle

22. Alcohol Fermentation
•Important for the regeneration of NAD+ under
anaerobic conditions
•Process common to microorganisms like yeast
•Yields neutral end products (CO
2
and ethanol)
•CO
2
generated impt in baking where it makes dough
rise and brewing where it carbonates beer.

23. Other Sugars can enter
glycolysis

24. How other sugars enter glycolysis
•Mannose can be phosphorylated to mannose-6-
phosphate by hexokinase and then converted to
fructose-6-phosphate by phosphomannose
isomerase.
•Fructose can be phosphorylated by fructokinase
to form fructose-1 phosphate (F-1-P). F-1-P
can then be converted to glyceraldehyde and
DHAP by F-1-P aldolase. Triose kinase then
converts glyceraldehyde to G-3-P.

26. -- GLYCOGENOLYSISGLYCOGENOLYSIS --
DEGRADATION OF GLYCOGEN
1. Release of glucose-1-phosphate
Enzyme = glycogen phosphorylase
non-
reducing  + PP
ii
ends 
glucose-1- + 
phosphate 

27.  always acts at nonreducingnonreducing end
 1,4 glycosidic link is cleaved
by phosphorylysis with retention of
energy potential in the phosphate
ester of glucose-1-phosphate.

28.  stopsstops at fourth glucose from a
1,6 branch point
 contrast with enzymes acting on
starch and glycogen in the gut, which
yield sugars, not sugar phosphates,
as products.
 activated by phosphorylation,
regulated by glucagon and
epinephrine

29. 2. Debranching - two parts
Enzyme = debranching enzymedebranching enzyme (both)
  a (16) link

transferasetransferase


Transfers chain of three glucoses to
anyany nonreducing end

30.  a (16) link

debranching enzyme
(glucosidase)

+
 = glucoseglucose
1,6 linkage cleaved1,6 linkage cleaved

32. 
glycogen phosphorylaseglycogen phosphorylase
or phosphorylase
for short

glucose-1-phosphate one at a time
as previously shown
-- phosphoglucomutase then yields
glucose-6-phosphate, which can
be dephosphorylated or enter
glycolysis.