CARBOHYDRATE (CHO) METABOLISM
PART 1
(Finals Period: MTCHEM2 Biochemistry for MLS)
AY: 2019-2020
At the end of this lecture, you should be able to:
1. Identify the reactions involved in Glycolysis
2. List the pathways for pyruvate metabolism
3. Calculate the energy yield from glycolysis
4. Describe the main features of Glycolysis, Glycogenesis
and Gluconeogenesis
Overview of CHO Metabolism:
• PART 1
o Introduction of CHO Metabolism
o Glycolysis
o Fates of Pyruvate
o Glycogenesis
• PART 2
o Glycogenolysis
o Gluconeogenesis
o Pentose Phosphate Pathway
o Hormonal Control of CHO Metabolism
INTRODUCTION TO CHO METABOLISM
Molecules of glucose is the focal point of carbohydrate
metabolism. Glucose is either oxidized to yield energy
or stored as glycogen. Sufficient oxygen, glucose is
totally oxidized to CO2 and H2O. Absence of oxygen,
glucose is only partially oxidized to Lactic acid.
▪ Aerobic Pathway- Needs oxygen
▪ Anaerobic Pathway- does NOT need oxygen
Digestion of carbohydrates is a biochemical process by
which food molecules, through hydrolysis, are broken
down into simpler chemical units that can be used by
the cells for their metabolic needs. It begins in the
mouth, where the enzyme Salivary α-amylase
catalyzes the hydrolysis of α-glycosidic linkage. This
enzyme is inactivated by the acidic environment of the
stomach. Primary site of carbohydrate digestion is
within the small intestine, where α-amylase is secreted
by the pancreas breaks down polysaccharide chain
into shorter and shorter segments until the
disaccharide maltose and glucose are the dominant
species. Final step in carbohydrate digestion occurs on
the outer membranes of intestinal mucosal cells.
Important disaccharidase enzymes are maltase,
sucrase and lactase. Furthermore, this process
produces three major breakdown products such as
Glucose, Galactose and Fructose.
Absorption of monosaccharide produced in
carbohydrate digestion is facilitated by protein
carriers which mediate the passage of the
monosaccharides through cell membrane.
Monosaccharides are then transported to the liver,
where fructose and galactose are rapidly converted to
glucose. Glucose produced are then metabolized to
produce ATPs which are needed by the cell as energy
for survival. Synthesis of ATPs involves several
metabolic pathways such as Glycolysis and
Gluconeogenesis.
GLYCOLYSIS
• the process where Glucose is converted into 2
molecules of pyruvate (a C3 molecule) and
chemical energy in the form of ATP is
produced;
• also reduced Nicotinamide Adenine
Dinucleotide (NADH) are produced
• a linear pathway that functions in almost all
cells.
• is an Anaerobic Pathway which involves
Oxidation process where the oxidizing agent is
the Coenzyme NAD⁺
• all enzymes needed for Glycolysis are present
in the cell cytosol.
Stages of Glycolysis:
A. 6-carbon stage (Energy-consuming stage)
• This stage is where the conversion of 2 ATP
molecules to 2 ADP molecules is used to
transform monosaccharides into
monosaccharide phosphates.
• Intermediates of this stage are Glucose or
Fructose derivatives.
• Steps 1 to 3 are under this stage.
B. 3-carbon stage (Energy-generating stage)
• This involves intermediates such as C3 –
phosphates where 2 of which are high-energy
species and all phosphorylated derivatives of
dihydroxyacetone, glyceraldehyde, glycerate
or pyruvate (derivatives of either Glycerol or
Acetone).
• In this pathway, loss of phosphate effects the
conversion of ADP molecules to ATP
molecules.
• Steps 4 to 10 are under this stage.
Legend in paragraph/bullets:
Yellow highlight Reactants in the rxn
Product produced in
Orange highlight the specific step
Purple highlight Enzyme used in rxn
Rxn under a specific
Underline step
STEP [1] Phosphorylation using ATP: Formation of
Glucose – 6 – Phosphate
• The step begins with phosphorylation of
glucose to yield glucose – 6 – phosphate.
• This step requires energy which is provided by
the breakdown of an ATP molecule where the
phosphate group attached to the glucose
molecule is from an ATP (ATP → ADP).
• This is catalyzed by the enzyme Hexokinase
and requires Mg₂⁺ ion for its activity.
Phosphorylation of glucose provides a way of
“trapping” glucose within the cell.
Miljun G. Catacata, RMT ; Sison, RMT | 1
 Step 1.

STEP [2] Isomerization: Formation of Fructose 6 –

Step 4.
Phosphate STEP [5] Isomerization: Formation of
• Through isomerization, Glucose–6– phosphate Glyceraldehyde 3 – Phosphate
is rearranged to fructose 6–phosphate,
• Of 2 molecules produced by the cleavage of
catalyzed by the enzyme
Fructose 1-6-bisphosphate, only
Phosphoglucoisomerase or Glucose 6- Glyceraldehyde 3-Phosphate is considered to
Phosphate Isomerase. be the substrate in the next reaction in
• With this reaction, Carbon 1 (C1) of the Glycolysis.
glucose is no longer part of the ring structure.
• On the other hand, Dihydroxyacetone
phosphate is readily converted into
Glyceraldehyde 3 – phosphate (Isomer),
maintaining the steady state concentration of
glyceraldehyde 3-phosphate. This reaction is
catalyzed by the enzyme Triosephosphate
isomerase.

Step 2.

STEP [3] Phosphorylation using ATP: Formation of

Fructose 1,6 – Bisphosphate

• ATP is the source of the phosphate and energy

in this stage where fructose-6-phosphate is
converted to fructose-1.6-bisphosphate
• This is catalyzed by the enzyme Step 5.
Phosphofructokinase-1(PFK-1).
STEP [6] Oxidation and Phosphorylation using Pi:
• In this step, Fructose molecule now contains 2
Formation of 1,3 – Biphosphoglycerate.
phosphate groups derived from ATP.
• In this rxn, a phosphate group is added to
glyceraldehyde 3 – phosphate to produce 1,3 –
biphosphoglycerate. The hydrogen of
aldehyde group becomes part of NADH.
• The source of the added phosphate is
inorganic phosphate (Pi).
• This reaction is catalyzed by the enzyme
Glyceraldehyde 3-Phosphate dehydrogenase.

Step 3.

STEP [4] Cleavage: Formation of 2 Triose

Phosphates
• This is the first step in “Energy-generating
Stage” of Glycolysis.
Step 6.
• In here, the reacting C6 species is split into 2
C3 (triose) species. Trioses (2) being produced STEP [7]. Phosphorylation of ADP: Formation of 3
in this step are not identical because fructose – Phosphoglycerate
1,6 – bisphosphate is unsymmetrical.
• These trioses-phosphate are: • In this step, the diphosphate species formed
✓ Dihydroxyacetone-phosphate (1,3-biphosphoglycerate) is converted back to
✓ Glyceraldehyde 3 – phosphate monophosphate species, producing ATP
• Reaction is catalyzed by the enzyme Aldolase. molecules.

Miljun G. Catacata, RMT ; Sison, RMT | 2

 • Carbon 1 (C1) phosphate group of 1,3 –
biphosphoglycerate is transferred to an ADP
molecule to form the ATP, catalyzed by
Phosphoglycerokinase.
• ATP production in this step involves
Substrate–level Phosphorylation where ATP is
produced from ADP through direct transfer of Step 10.
a high – energy phosphoryl group from a
reaction substrate to ADP. KEYNOTES:
• Step 3 is also known as the "rate-limiting step."
• Steps 1, 3, 10 are irreversible steps.
• Steps 7 and 10 are called substrate level
phosphorylation and they produce ATP.

SUMMARY OF GLYCOLYSIS:
Step 7.

STEP [8]. Isomerization: Formation of 2 –

Phosphoglycerate

• In this reaction, phosphate group of 3 –

phosphoglycerate is moved from carbon 3 to
carbon 2 producing 2-phosphoglycerate. This
reaction is catalyzed by the enzyme
Phosphoglycerate mutase which requires
magnesium (Mg2++) for its reactivity.

Step 8.

STEP [9]. Dehydration: Formation of

Phosphoenolpyruvate

• This step is an Alcohol dehydration reaction

resulting to the formation of another
compound containing a high – energy
phosphate group – Phosphoenolpyruvate;
catalyzed by Enolase which requires Mg2⁺⁺ for
its reactivity.

Entry of Galactose into Glycolysis

• In the liver, both Galactose and Fructose are
converted to intermediates that enter the
glycolysis pathway.
• Galactose begins with its conversion to
Step 9. Glucose 1 – Phosphate and converted to
glucose 6 – phosphate.
STEP [10] Phosphorylation of ADP: Formation of
Pyruvate
• In this step, substrate level phosphorylation
again occurs where Phosphoenolpyruvate
transfer its high – energy phosphate group to
an ADP molecule to produce ATP and
pyruvate.
• This reaction is catalyzed by enzyme Pyruvate
kinase which requires both Mg2⁺⁺ and K⁺.
• Two (2) ATP molecules are produced in this
step of Glycolysis.
Miljun G. Catacata, RMT ; Sison, RMT | 3
Entry of Fructose into Glycolysis
• Fructose involves phosphorylation by ATP to
produce fructose 1 – phosphate which then
split into 2 trioses.
• Glyceraldehyde must then be phosphorylated
by ATP to glyceraldehyde 3 – phosphate
before it enters the Glycolytic pathway while
Dihydroxyacetone phosphate enters
glycolysis directly.
Regulation of Glycolysis
STEP 1. Conversion of Glucose to Glucose 6 –
phosphate by the enzyme hexokinase –
inhibited by glucose 6 – phosphate.
STEP 2. Fructose 6 – phosphate is converted to
fructose 1,6 – biphosphate by
phosphofructokinase – inhibited by high
concentrations of ATP and Citrate
STEP 3. Conversion of phosphoenolpyruvate to
pyruvate by Pyruvate kinase – inhibited by
high ATP concentrations.
Fates of Pyruvate
Conversion of Pyruvate to a specific substance in the
metabolic pathway varies with cellular conditions
(aerobic or anaerobic conditions) and the nature of
the organism.
• Pyruvate is converted to Acetyl CoA- if under
aerobic condition
In Aerobic conditions, Pyruvate is oxidized to Acetyl
CoA. This process involves both Oxidation and
Decarboxylation where aside from acetyl CoA, CO2 is
also produced as a result of these reactions.
These reactions require NAD, CoA – SH, FAD and 2
other coenzymes (lipoic acid and thiamin
pyrophosphate).
• Lactate and to Ethanol- if under anaerobic
condition
In Anaerobic conditions pyruvate is reduced to lactate
via the process known as Lactic acid fermentation.
This involves conversion of NADH to NAD⁺.
The lactate is converted back to pyruvate when aerobic
conditions are again established in cell. The purpose of
this mechanism is to replenish NAD⁺ supplies in the
cell thus produces 2 pyruvate and 2 lactates.
Another Anaerobic reaction is the Ethanol
Fermentation. This process happens most frequently
in organism such as yeast, which possess the ability to
regenerate NAD through Ethanol.
This is an enzymatic anaerobic conversion of pyruvate
to ethanol and CO2. Conversion of pyruvate to ethanol
through decarboxylation reaction produces
Acetaldehyde, where if undergo reduction process can
produce ethanol.
ATP Production for the Complete Oxidation of
Glucose
NADH (produced from Step 6 of the Glycolytic
pathway) produced in the cytosol, cannot directly
participate in Electron Transport Chain (ETC) because
mitochondria are impermeable to NADH. A transport
system shuttles the electrons from NADH across the
cell membrane.
This shuttle involves dihydroxyacetone phosphate
and glycerol 3-phosphate. This process involves the
following steps:
1. Cytosolic reduction of dihydroxyacetone
phosphate by NADH to produce glycerol 3-
phosphate and NAD.
2. Glycerol 3-phosphate then crosses the outer
mitochondrial membrane where it is re-
oxidized through FAD to produce
dihydroxyacetone phosphate.
3. Regenerated dihydroxyacetone phosphate
diffuses out of the mitochondrion and returns
to the cytosol.
In these mechanisms, reduced FAD (FADH2) can
participate in the electron transport chain reactions
where 1.5 molecules, rather than 2.5 molecules of ATP
are formed for each cytosolic NADH.
The final number of ATP produced after this
process is 30, where 26 of which come from the
oxidative phosphorylation associated with the
ETC.
Miljun G. Catacata, RMT ; Sison, RMT | 4
 GLYCOGENESIS SUMMARY OF GLYCOGENESIS:

• Synthesis of Glycogen is facilitated via the

process known as Glycogenesis.
• In this process, glucose molecules that are not
utilized for ATP production is converted to
glycogen and stored in the Liver.
• Glycogen is synthesized from glucose 6 –
phosphate where the reaction requires 2
molecules of ATPs.
This involve the following reactions:
STEP [1]: Isomerization: Formation of Glucose 1 –
Phosphate

• In this reaction, Glucose 6-phosphate is

converted to Glucose 1-phosphate, catalyzed
by the enzyme Phosphoglucomutase.

---END OF CHO METABOLISM PART1---

Step 1.

STEP [2]: Activation: Formation of UDP – glucose

• Glucose 1 – phosphate from Step 1 must be

activated before it can be added to a growing
glycogen chain. This reaction requires Uridine
Triphosphate (UTP) as Activator. UMP is
transferred to glucose 1 – phosphate, and the
resulting PPi is hydrolyzed to 2Pi.

Step 2.

STEP [3]: Linkage to Chain: Glucose Transfer to a

Glycogen Chain

• UDP glucose produced from Step 2 is then

attached to the end of glycogen chain.

Step 3.
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