Biochemistry II Lecture 3

Topic: Carbohydrate Biosynthesis

What is metabolism?

Anabolism Vs. Catabolism

 Anabolic and catabolic pathways share a number of the same
reactions, but irreversible reactions are bypassed.
 Anabolic and catabolic pathways undergo coordinate control
 ATP hydrolysis drives biosynthetic processes even when the
precursors concentrations are low.
 Anabolic and catabolic pathways undergo coordinate control  ATP
hydrolysis drives biosynthetic processes even when precursor
concentrations are low. 
 Example of anabolic pathway = gluconeogenesis, the synthesis of glucose from non-
carbohydrate precursors, which helps to maintain glucose homeostasis.
Biochemistry II Lecture 3
Biochemistry II Lecture 3
Biochemistry II Lecture 3

Photosynthetic Carbohydrate synthesis

 Plants and photosynthetic microorganism, can synthesis carbohydrates from carbon

dioxide and water, reducing carbon dioxide at the expense of the energy and reducing
power furnished by the ATP and NADPH that are generated by light dependent reactions
of photosynthesis.
 Green plants contain in their chloroplasts unique enzymatic machinery that catalyzes the
conversion of carbon dioxide to simple (reduced) organic compounds, a process called
Co2 assimilation.

Role of glucose in the Human body

 Tissues that synthesize glucose are the liver and kidney.

 Tissues that use glucose as their primary source of energy are the brain, muscle,
erythrocytes and testes.
 When blood glucose levels rise, beta cells release insulin into the bloodstream.
 The insulin acts like a key, unlocking muscle, fat, and liver cells so glucose can get inside
of them.
 Glucose is the main source of energy for the brain. Nerve cells and chemical messengers
there need it to process information.

In what kind of situations do we need glucose?

Situations that require glucose include:

 Normal physiology situation:

1. Between meals and during sleep
2. Exercise/work
After heavy exercise or work (recycling of lactate)
After protein-rich diet (glycogenic amino acids)
Starvation (glycogenic amino acids)
Biochemistry II Lecture 3
Biochemistry II Lecture 3
Biochemistry II Lecture 3

The Glycolysis Cycle

 Glycolysis is derived from the Greek works: glucose- sweet or sugar; lysis-
dissolution.
 It is a universal pathway in living cells, elucidated in 1940.
 It is also referred to as the Embden-Meyerhof pathway (E.M, pathway) in honor of
the two biochemists that made significant contributions to the knowledge of
glycolysis.
Biochemistry II Lecture 3

Salient features:
 Glycolysis Is the stepwise degradation of glucose (and other simple sugars). It is the
major pathway for ATP synthesis in tissues lacking mitochondria e.g cornea,
erythrocytes.
 Glycolysis is a paradigm of metabolic pathways.
 Glycolysis takes place in all cells of the body. The enzymes of this pathway are
present in the closomal fraction of the cell.
 It is unique, in that it can function either aerobically or anaerobically, depending on
the availability of oxygen and the electron transport chain.
 In anaerobic conditions, lactate is the end product and in aerobic conditions pyruvate
is formed, which is then oxidized to CO2 and H2O.
 Glycolysis is essential for the brain. The glucose in brain has to undergo glycolysis
before it is oxidized to CO2 and H2O.
 Glycolysis (anaerobic) may be summarized by the net reaction:
Glucose + 2ADP + 2Pi ------+ 2lactate + 2ATP
 Glycolysis is the central metabolic pathway, with many of its intermediates providing
branch point to other pathways. Thus, the intermediates of glycolysis are useful for
the synthesis of amino acids and fats.
 Reversal of glycolysis along with the alternate arrangements of the irreversible steps,
will result in the synthesis of glucose)

Phases of Glycolysis
Aerobic phase: Oxidation is carried out by dehydrogenation and reducing equivalent is
transferred to the NAD+. Reduced NAD in presence of oxygen is oxidized in electron-transport
chain producing ATP.

Anaerobic phase: NADH cannot be oxidized in electron transport chain, so no ATP is produced
in the electron transport chain. But the NADH is oxidized to NAD+ by conversion of pyruvate to
lactate, without producing ATP. The anaerobic phase limits the amount of energy per mol of
Biochemistry II Lecture 3

glucose oxidized. Therefore, to produce a given amount of energy, more glucose must undergo
glycolysis under anaerobic conditions as compared to aerobic.

 The glycolysis pathway can be divided into three distinct phases:

 Energy investment phase/ priming phase
 Splitting phase
 Energy generation phase
Biochemistry II Lecture 3

1. Glucose is phosphorylated by ATP to form glucose 6-phosphate and ADP. This reaction
is catalyzed by the enzyme hexokinase.

2. Glucose 6-phosphate is converted into fructose 6-phosphate by phosphoglucose

isomerase. This isomerization involves the conversion of an aldose to a ketose.

3. Fructose 6-phosphate is phosphorylated by ATP to form fructose 1,6-biphosphate and

ADP. The enzyme catalyzing this step is phosphofructokinase (PFK).
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4. Aldolase splits fructose 1,6-biphosphate (6 carbon molecule) into two three-carbon

molecules, glyceraldehyde; glyceraldehyde 3-phosphate and dihydroxyacetone
phosphate.

5. Glyceraldehyde 3-phosphate is the only molecule that can be used for the remainder of
the glycolysis cycle. However, the dihydroxyacetone phosphate formed in the previous
step can rapidly be converted to glyceraldehyde 3-phosphate by triose phosphate
isomerase. This is an equilibrium reaction, as the glyceraldehyde 3- phosphate is used by
the rest of glycolysis, more dihydroxyacetone phosphate is converted to glyceraldehyde
3- phosphate as replacement. Thus effectively, for each molecule of fructose 1,6-
biphosphate that is cleaved in step 4, two molecules of glyceraldehyde 3-phosphate
continue down the pathway.
Biochemistry II Lecture 3

6. Glyceraldehyde 3-phosphate is converted to 1,3- bisphosphoglycerate. The reaction is

catalyzed by glyceraldehyde 3-phosphate dehydrogenase and uses inorganic phosphate
and NAD+. The other product is NADH. The energy for creating this new high-energy
phosphate bond comes from the oxidation of the aldehyde group of the glyceraldehyde 3-
phosphate.

7. The newly created high-energy phosphate bond of 1,3- bisphosphoglycerate is now used
to synthesize ATP. Phosphoglycerate kinase catalyzes the transfer of the phosphoryl
group from the 1,3-bisphosphoglycerate to ADP, generating ATP and 3-
phosphoglycerate.

8. 3-Phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase.

Thus, the reaction is a movement of the phosphate group to a different carbon atom
within the same molecule.
Biochemistry II Lecture 3

9. Enolase catalyzes the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate

(PEP). This reaction converts the low-energy phosphate ester bond of 2-phosphoglycerate
into the high-energy phosphate bond of PEP.

10. In the last reaction, pyruvate kinase

catalyzes the physiologically irreversible transfer of the phosphoryl group from PEP to
ADP to form ATP and pyruvate.
Biochemistry II Lecture 3
Biochemistry II Lecture 3
Biochemistry II Lecture 3

Fates of pyruvate
 Entry into the citric acid cycle
 Conversion to fatty acid or ketone bodies
 Conversion to lactate

Regulation of glycolysis
 The three enzymes namely hexokinase (glucokinase), phosphofructokinase and pyruvate
kinase, catalyzing the irreversible reactions to regulate glycolysis.
 Hexokinase is inhibited by glucose 6-phosphate. This enzyme prevents the accumulation
of glucose 6-phosphate due to product inhibition. Glucokinase, which specifically
phosphorylates glucose, is an inducible enzyme.
 The substrate glucose, probably through the involvement of insulin, induces glucokinase.
Phosphofructokinase (PFK) is the most important regulatory enzyme in glycolysis.
 This enzyme catalyzes the rate limiting committed step.
 PFK is an allosteric enzyme regulated by allosteric effectors. ATP, citrate and H+ ions
(low pH) are the most important allosteric inhibitors, while fructose 2,6- Bisphosphate,
ADP, AMP and Pi are the allosteric activators.
 Pyruvate kinase also regulates glycolysis. This enzyme is inhibited by ATP.