Metabolism involves the conversion of food molecules into energy and building blocks through chemical reactions in cells. There are two main types of metabolic pathways: catabolism breaks down molecules to release energy as ATP, while anabolism uses energy to construct complex molecules. ATP acts as the main energy currency, storing chemical energy in its phosphate bonds. Glucose undergoes several catabolic pathways including glycolysis, which breaks down glucose into pyruvate with net production of 2 ATP per glucose molecule. Pyruvate can then be further metabolized aerobically or anaerobically.

2. Introduction:
• Definition:
• Normally by metabolism we understand the process by which digested
foodstuff is converted to energy and building blocks of the body.
• In a simple word metabolism may be defined as all energy and material
transformation that occurs within living cells.
• In the biochemical point of view metabolism is a linked series of chemical
reactions in the body that begins with a particular molecule(s) and converts it to
another molecule(s) and energy is released or used in a carefully defined fashion.
•
• So the above definitions clearly states that two things happen here-
• One molecule is converted to another molecule.
• Energy is released or used in the process.

3. Metabolic pathways
Metabolic pathways can be divided into two broad classes-
Catabolism:
• It is the metabolic process/pathway via which the energy residing within the foodstuff is converted
to cellular energy.
• So catabolic reactions transform fuel (foodstuff) into cellular energy.
Anabolism:
• It is the metabolic process/pathway via which the building blocks of the body are synthesized from
simple molecules with input or use of energy.
There is a another path named amphibolic path which can be both anabolic or catabolic depending on the energy
of the cell.
Fuel/food/macromolecule
(carbohydrates, fats etc.)
CO2 + H2O +
Useful energy
Catabolism
Breakdown
Useful energy
+
Small molecules/
simple precursors
Complex
molecules
(DNA, protein,
etc.)
Anabolism

4. Useful energy/cellular energy
• Transformation of energy in living cells:
ATP is formed from ADP and Pi (i.e. AMP + PPi) when fuel molecules are oxidized in the body. Thus free
energy within food is converted to chemical energy in the form of ATP which is usable by the body. When
ATP breaks down the energy is released.
• Use of useful energy:
✓ The useful energy is used by the body for following purposes
✓ The performance of mechanical work in muscle contraction and cellular movements
✓ The synthesis of macromolecules and other biomolecules from simple precursors.
✓ The active transport of molecules and ions across the cell membrane.
✓ Nerve impulse conduction.
✓ Cell division and growth.
✓ Many other physiological functions which are necessary to maintain and propagate life.

5. ATP is the energy currency in the body:
It can be seen that ATP (Adenosine TRI Phosphate) is a nucleotide which is the combination of-
1. Adenine
2. Ribose sugar
3. Three phosphate radicals.

6. • As we can see that the last two phosphate groups are phosphoanhydride bonds. The amount of
free energy in each of these two high energy bonds is massive (7.3 kcal in standard condition and
12 kcal in normal biological condition). For example
• On the other hand, for glycerol-3-phosphate
• So we can see that a large amount of free energy is liberated when ATP is hydrolyzed to ADP and
Pi (orthophosphate) or when ATP is hydrolyzed to AMP and PPi (pyrophosphate) but in case of
glycerol-3-phosphate it is much less. This is because ATP has higher phosphoryl transfer potential
than glycerol-3-phosphate. This can be explained as follows-

7. • Electronic repulsion:
ATP contains in its structure four negatively charges, O─. These charges repel one another. In case of
ADP there are only 2 charges. So the repulsion is higher in ATP compare to ADP and thus ATP is less
stable to ADP and it contains more energy.
• Resonance stabilization:
The phosphate in ADP has greater number of resonance structure compare to the three phosphate
groups in ATP. Thus chance of stability is less in ATP.
As we can see that positively charged O and positively charged P are adjacent making it unstable.
So ATP is without a doubt a high-energy compound that can act as storage of chemical energy. It may be noted
that GTP and other nucleotides are also similar but ATP is still the primary cellular energy carrier especially
since two important electron carriers NAD+ and FAD are also derivatives of ATP.

8. Metabolism of carbohydrates:
The main pathways of carbohydrate metabolisms are
1.Anabolic pathways
✓ Glycogenesis
✓ Gluconeogenesis
2.Catabolic pathways
✓ Glycolysis
✓ Glycogenolysis
✓ TCA cycle

9. • The final products of carbohydrate digestion are
glucose, fructose and galactose.
• Among them galactose and fructose are
converted to glucose.
• Glucose is actively transported to the cells of wall
of intestine.
• Here active Na+-glucose co-transport mechanism
transports glucose along with Na+.
• Here glucose may be transported against
concentration gradient.
• This transport mechanism is functional in certain
cells (of GIT and Kidney).
• It may be noted that in the other tissues glucose
absorbed by facilitated diffusion.
Absorption of monosaccharides from intestine:

10. Interconversion of monosaccharides in liver cell:
Glucose, fructose and galactose are transported to liver by
portal blood. There the monosaccharides combine with UDP
(Uridine Di Phosphate). The following enzymes work here
Galactokinase works to convert galactose into galactose-1-
phosphate.
• Glucokinase works to convert glucose to glucose-6-
phosphate.
• Fructokinase works to convert fructose to fructose-6-
phosphate.
• Glucose-1-phosphate is converted to Uridine Di Phosphate
Glucose (UDPG) by the enzyme UDPG phosphatase. It may
be noted that UDPG is the active form of glucose that takes
part in glycogenesis.
• Glycogen is synthesized from UDPG by enzyme Glycogen
synthase.

11. Glycogenesis:
Glycogen:
• Glycogen is a readily mobilized storage form of glucose that exist as a large branched polymer of glucose that can be
broken down to yield glucose molecules when energy is needed.
• Two major sites of glycogen storage is liver and skeletal muscle. Although the concentration of glycogen is higher in
liver greater mass of glycogen is stored in skeletal muscle because of muscle’s much greater mass.
Structure:
• Most of the glucose molecules are linked by α-1, 4-glycosidic bonds and about every tenth residue branches exist
created by α-1, 6-glycosidic bond.
• It may be noted that in cellulose the bonds are β-linkages instead of α-linkages.

12. Glycogenesis:
• Glycogenesis is the process by which glucose molecules polymerize
to form glycogen in the cells.
• In the process of Glycolysis the glucose donor is UDP-glucose (UDPG)
which is the active form of glucose.
It is synthesized from glucose-1-phosphate and UTP via following
reaction catalysed by UDPG phosphorylase enzyme.

13. An enzyme called glycogen synthase catalyze the addition of glucose from UDPG to the terminal end of
the glycoside molecule as shown below.
• But glycogen synthase can add glucosyl residues (glucose) only to a polysaccharide unit containing more than four
residues. Thus there is a requirement for a primer.
• A protein named Glycogenin does the function of glycogen primer. Here a short polymer of glucose is formed which is
the glycogen primer.
• Now glycogen synthase can catalyze only the formation of linear polymer by α-1, 4-glycosidic bonds (called amylose).
Branching is done by another enzyme that catalyzes the formation of α-1, 6-glycosidic bond.
• This enzyme is called amylo α(1→4) to α(1→6) transglycosylase or glycosyl (4→6) transferase

14. • When there are at least 11 monomers in the amylose chain, this enzyme catalyses the transfer of
6 or 7 glucose residues of the terminal to the 6-C of the glucose residue more interior to the same
chain or different chain.
• Glucose residues may be added to the new branch by glucose synthase.

15. The whole process can be described as follows
Glucose
Glucokinase/
Hexokinase
Glucose-6-phosphate
Glucose-1-
phosphate
UTP
(Glycogen primer)n
(Glycogen)n+1
(Amylose chain)
Amylo α(1,4)→α(,6) transglycosylase
Glycogen
(Branched)
Phosphoglucomutase
UDPG phosphorylase
UDPG
Glycogen
synthase

16. Glycogenolysis:
• Glycogenolysis is the process or series of reactions by which cell’s stored glycogen is broken down to re-form
glucose in the cells.
• Glycogen is stored in all tissues specially in the liver cell and muscles.
• Normally this glycogen is not utilized. But if there is a long gap between meals and during exercise this glycogen
is utilized.
Process:
1. Glycogen phosphorylase enzyme is the key enzyme in
Glycogenolysis.
It catalyses the following reaction.

17. • But it alone can degrade glycogen to a limited extent.
• This is because this enzyme can only break down α-1, 4-glycosidic bond but not α-1, 6-glycosidic
bonds.
• So it stops cleaving glycogen four residues away from the branch point.
• Since there are about 1 residue of 10 residues is branched, this enzyme cleaves 6 residues.
• It may be noted that action of this enzyme requires pyridoxal phosphate as coenzyme.
• Two additional enzymes transferase and α-1, 6-glucosidase are required to break down branching.
• The transferase enzyme transfers three glucose residues from one branch to the other one
exposing the glucose residue joined by α-1, 6-glycosidic linkage.
• α-1, 6-glucosidase (branching enzyme) breaks the α-1, 6-glycosidic bond.

18. Thus free glucose molecule is released which is phosphorylated by hexokinase. So both the action of
glycogen phosphorylase and the debranching enzymes lead to the formation of glucose-1-phosphate.

19. 2. The glucose-1-phosphate is converted to
glucose-6-phosphate in a reaction catalysed
by phosphoglucomutase.
The intermediate step is the formation of
glucose-1, 6,-bisphosphate.
3.The glucose-6-phosphate may undergo Glycolysis or pentose (ribose) phosphate pathway.
Glucose-6-phosphate can also be converted to free glucose that enters the blood.
This is only possible by the action of an enzyme called glucose-6-phosphatase.
This enzyme is only available in three types of cells-
• Liver cells
• Intestinal epithelial cells
• Cuboidal epithelial cells
So only in these cells the conversion of glucose to glucose-6-phosphate is reversible. Since glucose captured in the
tissue cells they don’t need a reversible reaction. So phosphorylated glucose released from Glycogenolysis doesn’t
leave the cell other than from the above mentioned cells specially of liver.

20. Stored
glycogen
Transferaseα-1, 6-
glucosidase
Glycogen
phosphorylase
Glucose-1-phosphate
Glucose-6-phosphate
Phosphoglucomutase
Glucose-6-phosphatase
Glucose
(Enter blood)
Liver
Heart
Systemic
circulation
Facilitated
diffusion Glucose in cell Utilized
Blood circulation
Fructose-6-phosphate
Glycolysis
Ribose + NAPH
Pentose phosphate path
So the whole process can be described as follows-

21. Glycolysis:
• Glycolysis is the process or series of reactions that metabolizes one molecule of glucose into two
molecules of pyruvate (pyruvic acid) accompanied by a net production of two molecules of ATP.
• It is the most important mean of releasing energy from glucose molecule.
• The process occurs in 10 consecutive reactions and is anaerobic.
• The end products are processed anaerobically or aerobically.
• These reactions occur in the cytoplasm in case of eukaryotes.
Process:
1. Glucose enters the cell through facilitated diffusion. Then it is phosphorylated by 1 ATP to from glucose-6-
phosphate (G6P). This reaction is catalyzed by hexokinase or glucokinase (in liver). Why this is important is described
below under appropriate heading.

22. 2.Glucose-6-phosphate is isomerized to fructose-6-phosphate (F6P)in a reversible reaction catalyzed by phosphoglucose
isomerase.
3. Fructose-6-phosphate is phosphorylated to fructose-1, 6-bisphosphate (F-1, 6-BP).
This reaction is irreversible and catalyzed by phosphofructokinase (PFK). This enzyme is the pacemaker of Glycolysis.
This reaction requires one ATP.
[It should be noted that, when two separate monophosphoryl group (i.e. orthophosphate) are present in a
compound the prefix bis is used. On the other hand if the two groups are connected to each other then prefix di
is used.]

23. 4. Fructose-1, 6-bisphosphate is split
to two 3-carbon compounds
glyceraldehyde 3-phosphate (GAP)
and dihydroxyacetone phosphate
(DHAP). This reaction is readily
reversible and catalyzed by aldolase.
The reverse of the reaction is aldol
condensation hence the name
aldolase.
5. GAP (aldose) is the direct path
for Glycolysis meaning it proceeds
to the next reactions. But DHAP
(ketose) is not. It is interconverted
to GAP and then proceeds to
reaction. This isomerization is done
by the enzyme triose phosphate
isomerase (TPI). This reaction is
rapid and reversible.

24. 6. GAP is converted to 1,3-
bisphosphoglycerate (1, 3-BPG). This
reaction is reversible and catalyzed by
glyceraldehyde 3-phosphate dehydorgenase.
This reaction requires NAD+ as coenzyme.
It is important to notice that from each
GAP two hydrogen atoms are released
as (NADH + H+).
7. 1, 3-BPG is an energy rich molecule
with greater phosphoryl transfer
potential than ATP. So phosphoryl
group can be transferred from 1, 3-BPG
to ADP. This reaction is catalyzed by
phosphoglycerate kinase and it is
reversible.

25. 8. Rearrangement occurs to convert 3-phosphoglycerate to 2-
phosphoglycerate. The reaction is reversible and catalyzed by
phosphoglycerate mutase.
This occurs as follows
9. Dehydration causes the formation of an enol
phosphoenolpyruvate (PEP). Enolase catalyzes the
reaction. The reaction is reversible.
The PEP is energy rich and has high phosphoryl transfer
potential. This is because PEP (enol) is highly unstable and
wants to be stabilized to pyruvate (ketone).
10. Phosphoryl group is irreversibly transferred from
PEP to ADP and ATP is generated by the actions of
pyruvate kinase.

26. Calculation of energy production:
• The reaction (1) and (3) requires one ATP each giving a total of two ATPs used.
• Reaction (7) and (10) releases one ATP each. Thus from 1 glyceraldehyde 3-phosphate two ATPs are obtained.
• In reaction (5) DHAP was converted to GAP as well so basically from one glucose molecule we get two GAP
molecules.
• Thus one glucose molecules yields 4 ATPs in the Glycolysis process.
• Since two ATPs were used in the beginning of the reaction, the yield is two ATPs.
• The net reaction is
Importance of phosphorylation:
We saw at the beginning of Glycolysis that glucose upon entering the cell was phosphorylated to Glucose-3-phosphate.
This is important because-
• To capture glucose within the cell: Glucose-6-phosphate contains a charge and thus it can not be reabsorbed
outside the cell membrane because it is non-polar. Again glucose is transported inside the cell by means of
facilitated diffusion. Since glucose-6-phosphate is not a substrate for the carrier molecules glucose can’t leave cell.
• The addition of phosphoryl group destabilizes glucose. Thus it facilitates further metabolism.
• Hydrolytic breakdown of glucose will yield only one ATP, so much of energy will be wasted. On the other hand
phosphorylation helps to split glucose in many reactions which is energetically advantageous.

27. Metabolism of pyruvate:
There are three possible fate of pyruvate-
1. Formation of ethanol: This occurs in yeast and
several other microorganism. This process is
anaerobic meaning no oxygen will be required
for this reaction. this is called alcoholic
fermentation.
The total reaction is
2. Formation of lactic acid: This reaction takes place
in several microorganisms as well as higher
organisms (like human) when amount of oxygen is
limiting. The reaction is catalyzed by lactate
dehydrogenase and NADH act as coenzyme. This is
lactate fermentation.
The total reaction is

28. 3. Formation of
acetyl coA:
This reaction
occurs in
aerobic
conditions.
This occurs
inside of
mitochondria
as follows
This reaction is catalyzed by pyruvate
dehydrogenase complex.

29. TCA cycle (Tri Carboxylic Acid cycle)/Citric acid
cycle/Krebs cycle:
Introduction:
Glycolysis is an anaerobic process which can
harvest only a fraction (2 ATPs) of the energy available in
glucose. Most of the energy obtained by metabolism is
provided by aerobic process. This process starts with
complete oxidation of acetyl coA to CO2.
The process or series of reactions or cycle by
which the acetyl portion of the acetyl coA is degraded to
CO2 and hydrogen atoms and high energy of electrons
that will be used to power the synthesis of ATPs is called
TCA cycle.
The TCA cycle is the final common pathway for oxidation
of fuel molecules, all carbohydrates, fatty acids and amino
acids.The TCA cycle can be illustrated as follows

31. Process:
1. Oxaloacetate and acetyl coA are
condensed by citrate synthase to form
citric acid. This is an aldol condensation
reaction followed by hydrolysis.
2. Citrate is isomerized to isocitrate via cis-
aconitate intermediate. The reaction catalysed
by aconitase. Here H and OH are
interchanged.
3. Isocitrate is oxidized and decarboxylated to
α-ketoglutarate. The intermediate in this
reaction is oxalosuccinate. The reaction is
catalyzed by isocitric dehydrogenase.
See that a molecule of CO2 is removed.

32. 4. Oxidative decarboxylation of α-ketoglutarate yields
succinyl coA.
The reaction is catalyzed by α-ketoglutarate
dehydrogenase complex. It is an organized assembly of
three kinds of enzymes soing following functions-
- coA addition
- Decarboxylation
- Dehydrogenation
It may be noted that one molecule of CO is removed.
5. The thioester bond (CO-S) is cleaved and energy
released from this cleavage is used to phosphorylate a
purine nucleoside diphosphate, usually GDP. This reaction
is catalyzed by succinyl coA synthetase
We can see that GTP is formed rather than ATP. But
GTP is also an important component and it can convert
ADP to ATP.

33. 6. The succinate formed from succinyl coA is
oxidized to fumarate by the action of succinate
dehydrogenase enzyme.
The enzyme contains one molecule of FAD
covalently bonded. It is reduced to FADH2.
7. Fumarate is hydrated to L-malate. The reaction
is reversible and catalysed by fumarase. It is a
very sterospecific enzyme meaning reaction is
only reversed in case of L-malate.
8. L-malate is oxidized to oxaloacetate via reaction
catalyzed by L-malate dehydrogenase.