Department of Chemistry GFGC Chickballapur

METABOLISM
The word metabolism is a Greek word (metaboles-change or transformation) refers to
the sum total of the chemical reactions that is necessary for the food stuff to be utilised by
living organisms. Or all the chemical reactions in living cells are collectively called
metabolism.
Metabolism involves a number of reactions catalysed by a sequence of enzymes.
Such sequence of reactions are called metabolic pathway. The product of one reaction is the
reactant for the next reaction. The successive intermediates formed in metabolic pathway are
called metabolites.
There are 2 phases of metabolism 1. Catabolism 2. Anabolism
Catabolism - It is a degradative process in which large complex molecules like
carbohydrates, lipids and proteins from food are converted into simple building blocks
molecules like NH3, CO2 and lactic acid. During this process energy is released which is used
to synthesise of ATP.
Stages of metabolism
1. In the 1st stage large molecules are hydrolysed into the monomers.
Polysaccharide monosaccharides
Lipids fatty acids + glycerol
Proteins amino acids
2. In the 2nd stage, monomers are degraded to acetyl Co-enA by glycolysis and beta
oxidation pathway for fatty acids.
3. In the final stage products obtained in the II stage is oxidised to CO2 and H2O via
citric acid cycle, ETC and oxidative phosphorylation. A large amount of energy is
trapped in the form of ATP.

Anabolism - It is a reductive biosynthesis of molecules. It is a building up of metabolism.

The smaller and simple molecules are combined to form complex molecules. Its function is to
synthesise the molecules needed for cell membrane, growth and reproduction. Both
catabolism and anabolism occur simultaneously in cells.
Stages of anabolism
1. The simple molecules products in catabolism are converted to acetyl co-A. Acetyl
co-A serves as a common precursor for the synthesis of AA, sugars and fatty acids.
2. In the final stage, AA, sugars and fatty acids are assembled into complex
biomolecules like proteins, lipids and polysaccharides.

Carbohydrates metabolism
Carbohydrates are the important sources of energy. The digestion of starch starts in the
mouth by the action of enzymes salivary amylase. Then they undergo digestion in the
small intestine to small molecules like maltose, fructose glucose etc.
Glucose is the important sugar which can undergo several pathways.
1. Excess of glucose may be converted to glycogen and stored in liver and tissues.
2. Excess of glucose may be converted to AA, lipids and other carbohydrates.
3. Glucose may undergo oxidation in 3 ways
i. Glucose may be oxidised to pyruvate through glycolysis.
ii. Pyruvate may be oxidised to CO2 & H2O through citric acid cycle.
 iii. Glucose may be degraded stepwise to CO2 through sequence of reactions
involving pentose i.e. pentose phosphate pathway.

Glycolysis (glycol- glucose, lysis-cleavage)

It is a universal pathway of glucose metabolism in which 6 Carbon sugars are split
into 3 Carbon compounds with the release of energy. The sequence of reactions which
converts glucose to pyruvate enzymatically is called glycolysis. It takes place in cytoplasm of
the cell. Details of the pathway are worked out by biochemists Otto warberg, G. Embden and
Meyeroff. Hence the sequence of reactions is often referred as EM pathway.
It is an anaerobic oxidation of glucose to pyruvate which is oxidised to CO2 & H2O
in the citric acid cycle. This involves 10 enzyme catalysed reactions. It occurs in 2 stages.
1. Preparatory phase it is a 5 step reaction in which glucose is converted into 2 triose
phosphates by the utilisation of 2 ATP molecules.
2. Pay off phase in which triose phosphate is converted to 2 pyruvate with the release
of 4 ATP molecules.

Reactions of glycolysis
1. Phosphorylation of glucose – Glucose is a stable and neutral molecule and resists
breaking down. Hence glucose is activated by Phosphorylation. Glucose is
phosphorylated to glucose- 6 phosphate and the reaction is catalysed by the enzyme
hexokinase which is activated by Mg2+ ions.

2. Isomerisation of glu-6- phosphate to fructose phosphate

The second step of glycolysis involves the conversion of glucose-6-phosphate to fructose-
6-phosphate (F6P). This reaction occurs with the help of the enzyme phosphoglucose
isomerase (PI). The reaction involves the rearrangement of the carbon-oxygen bond to
transform the six-membered ring into a five-membered ring.
3. Phosphorylation of fructose-6-phosphate
It is the second phosphorylation reaction where fructose -6-phosphate is converted to
fructose- 1, 6-diphosphate by the enzyme Phosphofructokinase, with magnesium as a
cofactor.

4. Fructose- 1, 6-diphosphate undergoes cleavage at C3 –C4 to form 2 triose phosphates

catalysed by the enzyme aldolase to Dihydroxyacetone-phosphate and glyceraldehyde-3-
phosphate.

5. Isomerisation of dihydroxy acetone phosphate to glyceraldehyde -3 phosphate

 Only glyceraldehyde -3 – phosphate ca be utilised for the II phase of glycolysis. Hence
dihydroxy acetone phosphate is isomerised to gly-3- phosphate by triose phosphate
isomerase.

Preparatory phase of glycolysis converts a hexose molecule into 2 molecules of gly-3-

phosphate using 2 ATP molecules.
II phase of glycolysis
6. This is the first step to involve oxidation in which glyceraldehyde is oxidised and then
phosphorylated. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) dehydrogenates
and adds an inorganic phosphate to glyceraldehyde 3-phosphate, producing 1, 3
disphosphoglycerate.

7. Substrate level phosphorylation

It involves the transfer of high energy phosphate group from 1, 3 disphosphoglycerate to
ADP to yield 3- phosphoglycerate and ATP in the presence of enzyme phosphoglycerate
kinase. The phosphorylation of ADP to ATP in the presence of highly reactive
phosphorylated substrate is known as Substrate level phosphorylation. This is the first
step in glycolysis where ATP is produced.
8. Isomerisation
3- Phosphoglycerate is unable to transfer a phosphate group to ADP to form ATP. Hence
rearrangement of molecule takes place to form 2-phosphoglycerate catalysed by the enzyme
phosphoglycero mutase which transfers phosphate group from C3 to C2 position.

9. Dehydration of 2- phosphoglycerate.
2-phosphoglycerate is dehydrated to form the super energy compound phosphoenol pyruvate
by the enzyme enolase.

10. Conversion of phosphoenolpyruvate to pyruvate.

It is an irreversible step in which the transfer of a phosphate group from PEP to ADP to form
pyruvate and ATP. This is the second substrate level phosphorylation.

In this step 2 ATPs are produced per one glyceraldehydev-3- phosphate molecule. 2 ATPs
are used in the preparatory phase and 4 ATPs are generated in the payoff phase.

Steps 1 and 3 = – 2ATP (consumed)

Steps 7 and 10 = + 4 ATP (generated)
Net ATP produced in glycolysis = 2ATP

FATE OF PYRUVATE
Pyruvate formed on glycolysis has 3 different fates depending on the species of the organism
or metabolic conditions.

1. Conversion to lactate
Pyruvate is converted to lactate in aerobic tissues under anaerobic condition. This
happens in muscles during vigorous exercises. Due to lack of oxygen pyruvate is
reduced to lactate. This process is known as anaerobic glycolysis.
The enzyme lactate dehydrogenase catalyses the conversion of pyruvate to lactate.
The lactate will get converted to pyruvate when oxygen becomes available.

2. In some aerobic microorganisms, lactate is the normal product of glucose

metabolism. This takes place in the souring of milk. Large number of bacteria and
microbes can reduce pyruvate to lactate and such type of fermentation is known as
lactic acid fermentation.
3. Anaerobic condition – in yeast and microorganisms under anaerobic condition,
pyruvate is converted to ethanol and CO2. This process is called alcoholic
fermentation.
Pyruvate is decarboxylated to acetaldehyde by the enzyme pyruvate decarboxylase.
Acetaldehyde is converted to ethanol by alcohol dehydrogenase.
4. Glycolysis release only 7% of energy present in glucose. In aerobic organisms
pyruvate gets decarboxylated to acetate which gets oxidised to CO2 and H2O
through citric acid cycle, electron transport chain and oxidative phosphorylation in
the presence of oxygen. Before pyruvate can be fed into citric acid cycle, it must be
converted to acetyl co-A by the enzyme pyruvate dehydrogenase complex.
Acetyl co-A is an important link between anaerobic (glycolysis) and aerobic (citric
acid cycle) metabolic pathway.
 Citric Acid Cycle or Krebs cycle or TCA Cycle
It is the final pathway of oxidation of all fuel molecules like carbohydrates, proteins and
lipids. Han’s Adolf Kreb German biochemist elucidated the sequence of reactions of
oxidation of pyruvate to CO2 and H2O in 1937 and named after him. It is named as citric acid
cycle, since it is the first stable molecule that forms during the citric acid cycle. Since citric
acid is a tricarboxylic acid it is also called TCA cycle.
Citric acid cycle is a series of reactions in mitochondria where most of the enzymes
are present that bring about the complete oxidation of acetyl-coA A to CO2 and H2O. It is a10
step reaction.
1. Formation of citrate
The condensation of four-carbon oxaloacetate with acetyl-CoA takes place to form
citrate in the presence of enzyme citrate synthetase. The transfer of acetyl group
from acetyl-CoA to oxaloacetate takes place to form CoA and citrate.

2. Isomerisation of citrate to isocitrate

Citrate undergoes intramolecular rearrangement to form isocitrate and it is catalysed
by the enzyme aconitase. First it is dehydrated to form aconitate which is then hydrated to
form isocitrate. The overall effect of this conversion is that the –OH group is moved from
the 3' to the 4' position on the molecule

3. Oxidative decarboxylation of isocitrate to α-ketoglutarate

It is a 2 step reaction –
Isocitrate undergoes dehydrogenation to form oxalosuccinate, where 2H+ are removed
from substrate is accepted by NAD+ to form NADH+ and H+. Enzyme is isocitrate
dehydrogenase. Oxalosuccinate undergoes decarboxylation to form α- ketoglutarate.
 4. Oxidative decarboxylation of α-ketoglutarate to succnyl co-A
α -ketoglutarate loses a carbon dioxide molecule to form succinyl co-A and CO2 in the presence
of enzyme ketoglutarate dehydrogenase. The hydrogen atom released is accepted by NAD + to
form NADH and H+ which enters into ETC to form ATP and H2O

5. Succinyl-CoA is converted to succinate and CoASH

Succinyl -CoA is a high energy compound which undergoes hydrolysis to form succinate and
the reaction is catalysed by succinyl-CoA synthetase. The energy is coupled with
phosphorylation of GDP to GTP.

It is the only step where ATP is produced. By substrate level phosphorylation.

6. Oxidation of succinate

The enzyme succinate dehydrogenase catalyses the removal of two hydrogens from succinate
to form Trans isomer fumarate. In this process hydrogens are transferred directly from the
substrate to FAD without the participation of NAD+.

7. Conversion of fumarate to malate

In this reaction, the enzyme fumarase catalyses the addition of a water molecule to the
fumarate in the form of an –OH group to yield the molecule L- malate. The enzyme is highly
specific which act only on Trans isomer i.e. fumarate.

8. Oxidation of malate to oxaloacetate

In the final reaction of the citric acid cycle, oxaloacetate regenerated by oxidizing L–
malate with a molecule of NAD to produce NADH.

Oxaloacetate formed in the last reaction can condense with a new molecule of acetyl-CoA to
form citrate and thus the citric acid cycle continues. Overall reaction of citric cycle is

Energetics of kerb’s cycle

Each turn of kerb’s cycle produces 3 NADH &1 FADH2. Each NADH on oxidation yields 3
ATP molecules and each FADH2 yields ATP molecules. In addition one GTP is formed by
substrate phosphorylation.
Oxidation of 1 acetyl Co-A yields 3 NADH 3x3 =9ATP
1 FADH2 1x2 =2 ATP
1 GTP 1 ATP

TOTAL= 12 ATPs

Oxidation of 1 glucose molecule yield 2 acetyl Co-A s = 2x 12 = 24 ATP

TOTAL ENERGETICS OF CARBOHYDRATE METABOLISN

6 x3 =18 ATP
2 X2 =4 ATP
 1 X2 =2 ATP

TOTAL = (8+6+18+4+2)ATPs = 38 ATP

One molecule of glucose liberates 38 ATP molecules on oxidation

1 ATP gives 7000cals of energy

Therefore one molecule of glucose gives 38 x 7000 = 2,66,000 cals of energy