LEARNING GUIDES

CARBOHYDRATE METABOLISM
 Learning outcomes
You should be able to explain:
Glucose metabolism
1. Glycolysis vs Gluconeogenesis
2. Glycogenesis vs Glycogenolysis
3. Pentose phosphate pathway
CONTENT of study

1.Glycolysis
1.Phase 1
2.Phase 2

2.Gluconeogenesis
1.The reverse of glycolysis and bypass reactions
2.Major substrates
1.Lactate
2.Glycerol
3.Amino acid – alanine
4.Pyruvate

3.Glycogenesis
1.Synthesis of G-1-P
2.Synthesis of UDP-glucose
3.Synthesis of glycogen

4.Glycogenolysis
1.Removal of glucose from the non reducing ends of glycogen
2.Hydrolysis at branch points of glycogen
 QUICK Recall QUESTIONS
1.What is an ATP?
2.Why ATP is important?
3.Why ATP is an energy molecule?
4.Why do we need ATP in chemical
reactions?
 Review on Carbohydrate
• most abundant class of organic compounds
• originate as products of photosynthesis
n CO2 + n H2O + energy CnH2nOn + n O2
• classified according to the number of simple sugar units

What are the functions?

• Store energy in the form of starch (in plants) or glycogen (in animals & humans).

• Provide energy through metabolism pathways and cycles.

• Supply carbon for synthesis of other compounds.

• Form structural components in cells and tissues

e.g. the construction of the body organs and nerve cells

• The definition of a person's biological identity such as their blood group

Precursor: A molecule which exists as an ingredient, reactant, or intermediate in an anabolic pathway that
synthesizes a particular product. The molecule is described as the "precursor" of that product.
 CLASSIFICATION OF DIETARY CARBOHYDRATES
Monosaccharides Glucose, fructose, galactose
Disaccharides Sucrose, lactose, maltose
Oligosaccharides Maltodextrins, fructo-oligo-saccharides
Polysaccharides Starch: Amylose, amylopectin
Non-starch: Cellulose, pectins, hydrocolloids
Classes of carbohydrate

1. monosaccharide

• simplest sugar
glucose
• represent aldehydes or ketones of from 3-6
carbons in length.
• Glucose  "blood sugar"
• Fructose  "fruit sugar"
• Galactose the breakdown of lactose.
• Glyceraldehydes the metabolic breakdown
of Glucose.

D-glucose
(ring structure)
Conversion of glucose to other compounds
 Classes of carbohydrate

2. disaccharide

• made by connecting two simpler molecules.

•the removal of water from between the two molecules  condensation
 Classes of carbohydrate
3. polysaccharide • e.g. Starch, Cellulose, Chitin, Glycogen

a. Starch : 2 polyglucose

1. Amylose
- an unbranched
polyglucose that has α-
linkages at the C1 and C4
- quite soluble in water, but
only represents 20% of the
Starch.
2. Amylopectin
- highly branched with α-link at
the C1 and C6
- water insoluble and represents
the other 80% of the starch.
 Classes of carbohydrate

b. Cellulose

• fn: structural component

• held by glycoside links called ß-link.
• we lack of the digestive enzymes
• Herbivores and termites have microbes that produces the enzyme
• in human body, it helps keep the bowel functioning correctly
 Classes of carbohydrate

c. glycogen

• linkage similar to amilopectin BUT the branching is more numerous

• Our bodies make glycogen from the unused carbohydrate
• in form granules
• stored in the liver and muscle tissue of our bodies
• When the body needs energy sources  How to obtain the energy?

glycogen
When viewed with an electron microscope, glycogen particles are typically
arranged in chrysanthemum-like clusters of electron-dense particles
When stained with using the periodic acid-Schiff (PAS) technique, glycogen
stains bright pink in color.
The images below represent PAS-stained sections of liver from two mice:

Left : mouse that fasted Right: mouse that feed on food

overnight and thus had pallets two hours before fixing
very low levels the liver had high levels of
glycogen in liver. hepatic glycogen. These
accumulations are seen as pink
areas of PAS-positive material.
 Classes of carbohydrate

d. chitin

• Similar to cellulose in structure and

function
• BUT the unit = N-acetyl-ß-D-
glucosamine
• chitin has an amide group instead of
a hydroxyl group (alcohol)

Chitosan is very similar to chitin.

Chitosan has an amine group
instead of an amide group.

This just means that chitosan

doesn't have any carbons double
cellulose
bonded to oxygen and chitin
does.
 GLUCOSE METABOLISM

Produce/provide from pyruvate

gluconeogenesis

Energy
storage Glucose Need energy
glycogenesis glycolysis
(carbohydrate)

glycogenolysis

Produce/provide from glycogen

Major pathways in carbohydrate metabolism

1. Glycolysis
2. Gluconeogenesis
3. Glycogenesis
4. Glycogenolysis
5. Pentose phosphate pathway
 GLUCOSE METABOLISM

Pathway General function Is activated when:

Glycolysis Glucose  2 Pyr • E is needed

Makes 2 ATP, @ NADH • Aerobic @ anaerobic
Gluconeogenesis Pyr  glucose • Liver needs to raise blood sugar levels
Requires 4ATP, 2GTP • Liver glycogen is depleted
• Can occur in liver & kidney
Glycogenolysis Glycogen  glucose • Muscles need glucose for E
• Liver needs to raise blood sugar levels
Glycogenesis Glucose  glycogen • Glucose is in Xs
Requires 1 UTP/ glucose
Pentose Glucose-6-P  ribose-5-P, • NADPH is needed for lipid synthesis
phosphate other sugars • Ribose is needed for nucleotide
pathway Makes 2 NADPH synthesis
Glucose metabolism

Glycolysis Gk. glykeros, sweet ; lyo, loose,dissolve

•Sugar is broken down to form Energy (ATP)

•can occur aerobically or anaerobically
• there are 4 important events occur:

1. Substrate level phosphorylation : phosphate groups from ATP are transferred to

glucose
2. 6C molecule (glucose) is broken down into two 3C molecules.
3. 2 electrons are transferred to the coenzyme NAD
4. Energy is captured in ATP
First phase of glycolysis
Glucose

ATP
Hexokinase
1. Glucose is phosphorylated to
form activated molecule Glucokinase ADP

Glucose- 6-P
Glucose
2. Rearrangement phosphate
isomerase

Fructose- 6-P
ATP
3. Second phosporylation Phosphofructokinase
ADP

Fructose-1,6- bisphosphate

Second phase of glycolysis

Second phase of glycolysis
Fructose-1,6- bisphosphate
4. 6C molecule is split into
two 3C PGAL molecules aldolase

Dihydroxyacetone D-glyceraldehyde-3-phosphate (G3P/PGAL)

phosphate (DHAP)
Triosephosphate 5. Oxidation followed by Glyceraldehyde-3-phosphate
isomerase phosphorylation
D-glyceraldehyde-3-phosphate
(G3P/PGAL)
6. phosphate group
is removed
7. phosphate group
is rearranged
P NAD+
dehydrogenase
NADH + H+
1,3-bisphosphoglycerate (BPG/PGAP)
ADP
Phosphoglycerate kinase
ATP
3-phosphoglycerate (3PG/PGA)
Phosphoglyceromutase

2-phosphoglycerate (2PG)
8. Oxidation by Enolase
removal of water H2O

Phosphoenolpyruvate (PEP)
9. phosphate group ADP
is removed Pyruvate kinase

Pyruvate ATP
Pyruvate
Glucose
metabolism

Inputs Outputs
If aerobic respiration
Glucose 2 pyruvate occur  pyruvate will
2 NAD+ 2 NADH experience further
breakdown in transition
2ATP 4 ATP
reaction & Krebs Cycle.
(net 2 ATP)
2 ADP + 2P If anaerobic respiration
occur  pyruvate will
experience further
breakdown in fermentation
 What happen if glycolysis could not occur?

Hypoglycemia (low blood sugar) is a condition in which there

is an abnormally low level of glucose (sugar) in your blood.

• Glucose phosphate isomerase (GPI) is involved in the transformation of glucose 6

phosphate into fructose 6 phosphate. GPI deficiency is an autosomal recessive inherited
condition usually resulting in chronic hemolytic anemia
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency, lack of enzyme that is produced
by red blood cells and helps the body process carbohydrates, turning them into energy.
Glucose
metabolism

Glycolysis vs Gluconeogenesis

Gluconeogenesis occur when blood

sugar levels are low & liver glycogen is
depleted.
Substrates for gluconeogenesis:

1. Amino acid
2. Lactate
3. Glycerol
4. Pyruvate
Glucose
metabolism

• Gluconeogenesis = genesis of new glucose

• Anabolic pathways : synthesize glucose from amino acids, lactate, & glycerol
• Requires E
• Important because brain & RBC need a steady supply of glucose

fat-rich
fat-rich diets
diets are
are not
not only
only bad
bad for
for your
your heart,
heart,
they
they may
may alsoalso impair
impair essential
essential brain
brain functions
functions
like
like concentration
concentration and and memory.
memory. The The
researchers
researchers compared
compared the the cognitive
cognitive function
function
of
of rats
rats on
on aa high-fat
high-fat diet
diet with
with rats
rats on
on lower
lower fat
fat
feed.
feed. After
After three
three months,
months, thethe rats
rats on
on the
the high-
high-
fat diet showed severe impairment
fat diet showed severe impairment on a wide on a wide
range
range of of learning
learning and
and memory
memory taskstasks relative
relative to
to
those animals that consumed the
those animals that consumed the lower fat lower fat
diet.
diet. The
The research
research also
also showed
showed that
that giving
giving
glucose
glucose to to the
the high-fat
high-fat rats
rats significantly
significantly
improved
improved their their memory.
memory.
Glucose
metabolism
Gluconeogenesis
• Occurs primarily in liver after glycogen is depleted
• it appear as the reverse of glycolysis except for the reactions that
bypass the three irreversible reactions of glycolysis.
• But thermodynamically impossible

Irreversible reaction in glycolysis are:

1. Glucose  glucose-6-phosphate
2. Fructose-6-phosphate  fructose-1,6-biphosphate
3. PEP  pyruvate

How to overcome/bypass this problems ?

Glucose
metabolism

Gluconeogenesis can bypass 3 reXns in glycolysis by:

1. Formation of glucose
glucose + ATP  glucose-6-P + ADP [glycolysis]
Glucose-6-P + H2O glucose + Pi

2. Formation of fructose-6-P
fructose-6-P + ATP  Fructose-1,6-biphosphate + ADP [glycolysis]
Fructose-1,6-biphosphate + H2O  fructose-6-P + Pi

3. Formation of PEP
PEP + ADP  Pyr + ATP [glycolysis]
Pyr + CO2 + ATP + H2O  OAA + ADP + Pi
OAA + GTP  PEP + GDP + CO2
Glucose
metabolism Major substrates for Gluconeogenesis (including Pyruvate)

1. Lactate
Released when RBC or other cells [lack mitochondria] have low oxygen
conc.
e.g. in Cori cycle :
- lactate is produced in muscle cells under anaerobic condition.
- lactate is transferred to liver
- reconverted to pyruvate by lactate dehydrogenase
- pyruvate is converted to glucose by gluconeogenesis

gluconeogenesis

lactate
dehydrogenase
Glucose
metabolism

2. Glycerol
A product of fat metabolism
Transported to liver in blood
Converted to glycerol-3-phosphate by glycerol kinase (only found in liver)
Glycerol-3-P is converted by oxidation to form DHAP when cytoplasmic NAD+
is high {glycerol phosphate dehydrogenase]

3. Amino acids
Referred as glucogenic amino acids
Most important = alanine
When exercising muscle produces high pyruvate,
Pyr can be converted to alanine by transamination
Pyr + glutamate  alanine + α-ketoglutarate [alanine transaminase]
Alanine is transported to liver to form pyruvate
Glucose
metabolism

transamination
Glucose
metabolism

Glycogenesis = genesis of glycogen

Glycogenin (primer protein) initiates glycogen formation
In muscle : Xs glucose is stored as glycogen
In liver : glucose is removed from blood in response to insulin

Glycogenolysis = degradation of glycogen

In muscle : glycogen is degraded to G-6-P for E
In liver : - glycogen is degraded to produce free glucose for export
 Glycogenensis vs Glycogenolysis

LIVER

glucose is removed glycogen is degraded

from blood in to produce free
response to insulin glucose for export

Glycogenesis genesis Glycogenolysis

of glycogen degradation of glycogen
Glycogenin
(primer
protein)
initiates
MUSCLES
glycogen
formation excess of glucose is glycogen is degraded glucagons
stored as glycogen signals low
to G-6-P for E blood sugar
&
epinephrine
for
immediate
need for E
Glucose
metabolism
Glycogenesis
1. Synthesis of G-1-P
G-6-P  G-1,6-P  G-1-P
2. Synthesis of UDP-glucose
G-1-P + UTP (uridine triphosphate)  UDP-Glucose + PPi
3. Synthesis of glycogen
Glycogen (n residues) + UDP-glucose  glycogen (n+1 residues)+ UDP
Carbohydrates are often stored as glycogen in the body
•There are many types of recognized glycogen storage diseases

http://emedicine.medscape.com/article/1116574-overview
 Glycogenolysis

How to form this to that ?

Glucose
metabolism

Glycogenolysis involves:

Requires two reactions:

1. Removal of glucose from the nonreducing ends of glycogen on the
outer branches
glycogen  G-1-P
2. Hydrolysis at branch points of glycogen by debranching enzyme.
glucose is then transported to bloodstream or for glycolysis

http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/glycogen.htm
#animat1
Glucose
metabolism
Pi

Glycogen
phosphorylase
Glucose
metabolism H2O

Transferase
& Glycogen
debranching debranching
site enzyme

H2O

Amylo-α(1,6)-glucosidase
Glucose
metabolism
H2O

glucose

Pi

Glycogen
phosphorylase

x7
 Pentose phosphate pathways: oxidation of G-6-P

Fn:
1. To make NADPH for synthesis & prevent oxidative damage
2. To make sugar intermediates esp. ribose-5-phosphate

Location :
cytoplasm, esp in cells that synthesize lipids & cells at high risk of oxidative damage
In plants during dark reXn of photosynthesis
Function
Oxidative
 NADPH production
phases
 Reducing power carrier  Reactions
 Synthetic pathways producing NADPH
 Role as cellular  Irreversible
antioxidants Non-oxidative
 Ribose synthesis phases
 Nucleic acids and  Produces ribose-
nucleotides 5-P
 Reversible
reactions feed to
glycolysis
Demand for NADPH
 Biosynthetic pathways
 FA synthesis (liver, adipose, mammary)
 Cholesterol synthesis (liver)
 Steroid hormone synthesis (adrenal, ovaries, testes)
 Detoxification (Cytochrome P-450 System) – liver
 Reduced glutathione as an antioxidant (RBC)
 Generation of superoxide (neutrophils)
Glucose
metabolism
Step learning 2 Activities
What is the
connection between :
Look up in your references.
1.Glycolysis Draw a connecting map of all four
2.Gluconeogenesis processes to glucose.
3.Glycogenesis Label the connecting link correctly
4.Glycogenolysis
Checking task

Fill in the correct term for each process

a.When human blood sugar level is low and glycogen in the liver is depleted,
___________________ takes place to restore the glucose level in blood

b.The situation of having excess sugar in the blood may be balanced by storing
them through the process of ___________________

c.________________ occurs when we need to raise glucose level in our blood

d.We have vast source of energy in our body that can be tapped when needed via
the process of ____________________

e.__________________________ and ____________________ produce glucose

at the end of their processes.

f.__________________________ and ____________________ use glucose as

their starting material in the process
g. ______________ produces Pyruvate whilst ____________ uses Pyruvate

h. ______________ produces Glycogen whilst ____________ uses Glycogen

i. Which process produce energy molecules?

j. Which process require energy molecules?

k. Complete the reverse pair below:

_____________________  Glycogenesis

Gluconeogenesis  __________________________
Step learning Activities
3
What is 1. List the importance of Glycolysis to living
Glycolysis? organisms
2. List the four important events in Glycolysis
3. In a table format, list all inputs and outputs for
Glycolysis
4. Animation :
http://highered.mcgraw-
hill.com/sites/0072507470/student_view0/chapter2
5/animation__how_glycolysis_works.html

5. Study your reference for details and build a

map/model to demonstrate the process. Prepare
the following representing models: 6C sugar, G6P,
F6P, F1,6-P, ATP, ADP, Phosphate, NADH, NAD,
DHAP, PGAL, PGAP, PGA,2PG, PEP, Pyr and any
relevant figures
6. Label the stage of producing and requiring energy
molecules in/on your model
7. Identify all irreversible reactions
8. Create a method to write the flow of glycolysis
correctly
9. Ask your friend to predict the following step to a
Checking task
1.In glycolysis, glucose is converted to _______________

2.The NET result of a single glycolysis run is the formation of _________

3.Under anaerobic conditions, the end-product of glycolysis is converted to _________________

4.During glycolysis, a 6-carbon sugar diphosphate molecule is split into two 3-carbon sugar phosphate
molecules. TRUE or FALSE

5.Under aerobic conditions, the end-product of glycolysis is further reduced to yield more ATP. TRUE or FALSE

6.What are the major differences and similarities of phase 1 and 2 in glycolysis?

7.Energy production in phase 2 involves a similar reaction. State the reaction

8.Predict the total of energy molecules from 3 molecules of glucose.

9.If cellular level of ATP is increased, what happen to the following enzymes: pyruvate kinase;
phosphofructokinase; hexokinase

10.Substrate level phosphorylation is one of the reactions occur in Glycolysis. What is the significance of the
reaction?

11.State TWO substrate that involved in producing ATP in glycolysis.

12.There are THREE irreversible reactions in glycolysis. State all reactions.

Step learning Activities
4
What is 1. Refer to the model you prepared in Step learning
Gluconeogenesis 3. Rearrange the whole model starting from the
? bottom molecule formed, i.e Pyruvate to form
glucose. Label the pathway
2. You may “flow back” using the reversible
pathways. Find out how to “flow back” at the
irreversible pathways.
3. Complete the solution table below
Flow-blocker Bypass

4. List the resources as substrates to form glucose

and label them in your map/model
5. List the regulators for gluconeogenesis
Checking task

1. Gluconeogenesis is an anabolic / a catabolic pathway.

2. How are glycolysis and gluconeogenesis differ?

3. How are glycolysis and gluconeogenesis similar?

4. There are three reactions in glycolysis that are not used in gluconeogenesis.
What do the three reactions have in common?

5. Place the following enzymes in the correct category

- PEP carboxykinase, Aldolase, malate dehydrogenase, hexokinase,
glucose-6-phosphatase, pyruvate kinase, phosphoglycerate kinase,
enolase, phosphofructoskinase

Category Enzymes
Use in glycolysis
Use only in gluconeogenesis
Use in both
Step learning 5 Activities
Major substrates for 1. List down all major substrates
gluconeogenesis 2. Fill in the blanks

In Cori cycle:
___________ is produced in muscle cells under
____________condition. ____________ is
transferred to ____________and reconverted
to _______________by the enzyme
________________. Finally it is converted to
glucose by gluconeogenesis

In Alanine cycle:
When exercising muscle produces
_______________. This can be converted to
________________by transamination using the
enzyme __________________________. Then,
____________________ is transported to liver
to form _______________. Finally it is
converted to glucose by gluconeogenesis.
Step learning 5 Activities
(cont)
Major substrates for Glycerol
gluconeogenesis
Glycerol is a ___________metabolism product. It
will be sent to ____________ in blood. Then
_________________ is converted to
_____________________ using the enzyme
_______________________ which can only be
found in liver. ______________________ is
further converted to ______________________
by the process of ______________________.
This occurs when ________________________ is
high. The enzyme involved is
____________________________.

Pyruvate

Refer to your map. Write all word equations to

show the production of glucose.
Checking task

1. When red blood cells have low oxygen concentration, human body
will need to raise glucose level in order to maintain the steady
supply. Explain how body reacts.

2. How does the glucose-alanine cycle allow muscle pyruvate to be

used for liver gluconeogenesis and subsequently returned to
muscles as glucose?

3. How many bypass reactions occur to form glucose from glycerol?

State in which reactions.
Step learning 6 Activities
What is 1. What is the type of metabolism for
glycogenesis? glycogenesis?
2. Write the definition of glycogenesis
3. List the situations that promote
glycogenesis
4. Where is the location for glycogenesis
5. Write the sequence of enzymes involved in
glycogenesis
6. Draw and label the reactions involved in
glycogenesis
Checking task

1. State the importance of glycogenesis

2. List the main the substrate(s) for the process
3. In which situation will trigger glycogenesis?
Step learning Activities
7
What is 1. What is the type of metabolism for
glycogenolysis? glycogenolysis?
2. Write the definition of glycogenolysis?
3. List the situations that promote glycogenolysis.
4. Where is the location for glycogenolysis?
5. Draw and explain the reactions involved in
Figure
glycogenolysis using the explanation
table below

6. Compare and contrast glycogenesis and

glycogenolysis
Criteria Glycogenesis Glycogenolysis
Checking task

1. State the importance of glycogenolysis

2. List the main the substrate(s) for the process
3. State the two major reactions in the process
4. Predict the following end products from the figure of glycogen
below

5. What triggers glycogenolysis?

Which Step Learning needs extra attention
from you?

Step learning Content

1 What is carbohydrate?
2 What is the connection between :
1.Glycolysis
2.Gluconeogenesis
3.Glycogenesis
4.Glycogenolysis
3 What is Glycolysis?
4 What is Gluconeogenesis?
5 Major substrates for gluconeogenesis
6 What is glycogenesis?
7 What is glycogenolysis?