METABOLISM

-MUKESH DHITAL
ASST.PROF.CLINICAL BIOCHEMISTRY

BY:MUKESH DHITAL
• Metabolism is defined as the sum total of all the
chemical reactions or chemical transformations that are
taking place in the body.
• Metabolism is derived from a Greek word, metabellein,
which means “to change”. It includes the process by which
cells use food material to obtain energy, store excess
calories for future use and build up various substances.
• Metabolism thus includes fuel oxidative pathway,fuel
storage and mobilization pathway,biosynthetic pathway
and pathway of detoxification and excretion of
unnecessary compounds.

BY:MUKESH DHITAL
• Living system is open and maintains steady
state where metabolites flow tend to be
unidirectional.
• Metabolic reactions do not occur in isolation,
or in a random or haphazard manner. Rather
they are organized into multi-step enzyme
catalyzed reaction sequences called metabolic
pathways.

BY:MUKESH DHITAL
• Metabolic pathways are series of consecutive
enzymatic reactions that produce specific
products.
• Their reactants, intermediates,and products
are referred to as metabolites.
• As an organism utilizes many metabolites, it
has many metabolic pathways

BY:MUKESH DHITAL
• Each reaction forms just one step in a metabolic
pathway
• In metabolic pathways, the product of one
reaction serves as a substrate for the next one;
the product of second reaction is substrate for
the third reaction, and so on.
• Each of the consecutive steps in a metabolic
pathway brings about a specific small chemical
change, usually the removal, transfer, or addition
of a particular atom or functional group
BY:MUKESH DHITAL
METABOLISM IN SENSE OF ENERGY
• Metabolism is the organized release or capture of
small amounts of energy in processes whose
overall change in energy is large
• Combustion of glucose in a bomb calorimeter
results in an uncontrolled, explosive release of
energy in its least useful form, heat.
• The ten reactions of glycolysis, the nine reactions
of the citric acid cycle, and the successive linked
reactions of oxidative phosphorylation release
the energy of glucose in a stepwise fashion and
the small “packets” of energy appear in ATP.

BY:MUKESH DHITAL
 TYPES OF METABOLIC PATHWAYS
• The reaction pathways that comprise metabolism are
often divided into two categories:
1. Catabolism, or degradation, in which energy rich
nutrients and cell constituents are broken down
exergonically into smaller simpler molecules to
generate free energy some of which is conserved in
the formation of ATP and reduced electron carriers
(NADH, NADPH, and FADH2); the rest is lost as heat.
2. Anabolism, or biosynthesis, in which biomolecules are
synthesized from simpler components.

BY:MUKESH DHITAL
• Anabolic reactions require an input of energy, generally in
the form of the phosphoryl group transfer potential of ATP
and the reducing power of NADH, NADPH, and FADH2.
3.Amphibolic pathways are seen at cross roads of
metabolism,where both anabolic and catabolic pathways
are linked.
Catabolic and anabolic pathways of a particular
biomolecule are not the exact mirror images.Anabolic and
catabolic pathways follow distinct, thermodynamically
spontaneous chemical paths that utilize unique metabolic
intermediates.

BY:MUKESH DHITAL
The free energy released by catabolic processes is conserved through the
synthesis of ATP from ADP and phosphate or to form NADPH
ATP and NADPH are the major free energy sources for anabolic pathways

BY:MUKESH DHITAL
BY:MUKESH DHITAL
• Some metabolic pathways are linear, and some are
branched, yielding multiple useful end products from a
single precursor or converting several starting materials
into a single product.
• In general, catabolic pathways are convergent and
anabolic pathways divergent .
• Some pathways are cyclic: one starting component
of the pathway is regenerated in a series of reactions
that converts another starting component into a
product.

BY:MUKESH DHITAL
DIVERGENCE AND CONVERGENCE

BY:MUKESH DHITAL
 STAGES OR PHASES OF METABOLISM
• The degradation of foodstuffs to yield energy
occurs in three stages.
i. The first stage is called primary metabolism
.Here digestion in the gastrointestinal tract
converts the macromolecules into small units.

BY:MUKESH DHITAL
• Hydrolysis of complex molecules is thus a
major feature of primry metabolism
• Proteins are degraded to amino acids,
polysaccharides to monosaccharides, and fats
(triacyl glycerols) to free fatty acids and
glycerol.

BY:MUKESH DHITAL
II.SECONDARY OR INTERMEDIARY METABOLISM:
The digested products are absorbed, catabolized
to smaller components, and ultimately oxidized
to CO2.It has 2 steps :
A. Thus Conversion of building blocks to simple
intermediates which are further degraded to
acetyl coenzyme A (CoA)
B. Acetyl coA enters the TCA cycle (the final
common oxidative pathway), and The reducing
equivalents NADH or FADH2 are generated in the
mitochondria

BY:MUKESH DHITAL
• Some energy is captured as ATP, but the
amount is small compared with the energy
produced during the third stage of
metabolism.

BY:MUKESH DHITAL
III. Reduced equivalents then enter into the
electron transport chain (ETC, or Respiratory
chain), where energy is released. This is the
tertiary metabolism or Internal respiration or
cellular respiration

BY:MUKESH DHITAL
BY:MUKESH DHITAL
 ANABOLISM
• Anabolic reactions or anbolism combine
small molecules, such as amino acids, to form
complex molecules, such as proteins
• Relatively few metabolites, mainly pyruvate,
acetyl-CoA, and the citric acid cycle
intermediates, serve as starting materials for a
production of varied biosynthetic products.

BY:MUKESH DHITAL
• Anabolic reactions require energy (are
endergonic), which is generally provided by
the breakdown of ATP to adenosine
diphosphate (ADP) and inorganic phosphate
(Pi).
• Anabolic reactions often involve chemical
reductions in which the reducing power is
most frequently provided by the electron
donor NADPH
BY:MUKESH DHITAL
 FIVE PRINCIPAL CHARACTERISTICS OF
METABOLIC PATHWAYS
1. Metabolic pathways are irreversible..
• In a metabolic pathway there may be steps
having positive free energy change which disturbs
the directionality of pathway towards its specific
product formation.
• In a multi step pathway thus there would be an
irreversible highly exergonic reaction (having a
large negative free energy change) as a part of it
which makes the entire pathway irreversible and
provides a direction of a pathway
BY:MUKESH DHITAL
2. Catabolic and anabolic pathways must differ.
• If two metabolites are metabolically
interconvertible, the pathway from the first to
the second must differ from the pathway
from the second back to the first:

BY:MUKESH DHITAL
• The existence of independent interconversion
Routes, is an important property of metabolic
pathways because it allows independent control
of the two processes.
• If metabolite 2 is required by the cell, it is
necessary to “turn off” the pathway from 2 to 1
while “turning on” the pathway from 1 to 2.
• Such independent control would be impossible
without different pathways.
BY:MUKESH DHITAL
3. Every metabolic pathway has a first
committed step.
• Early in each pathway, however, there is an
irreversible (exergonic) reaction that
“commits” the intermediate it produces to
continue down the pathway.

BY:MUKESH DHITAL
4.All metabolic pathways are regulated. Metabolic
pathways are regulated by laws of supply and
demand.
In order to exert control on the flux of
metabolites through a metabolic pathway, it is
necessary to regulate its rate-limiting slower step
• Since most of the other reactions in a pathway
function close to equilibrium, the first committed
step is often one of its rate-limiting steps
BY:MUKESH DHITAL
5. Metabolic pathways in eukaryotic cells occur
in specific cellular locations.
The compartmentation of the eukaryotic cell
allows different metabolic pathways to
operate in different locations.

BY:MUKESH DHITAL
COMPARTMENTALISATION

BY:MUKESH DHITAL
REGULATION OF METABOLIC PATHWAY
• The pathways of metabolism must be coordinated so that the
production of energy or the synthesis of end products meets
the needs of the cell.Mechanisms:
A. Signals from within the cell (intracellular)
• The rate of a metabolic pathway can respond to regulatory
signals that arise from within the cell. For example, the rate of
a pathway may be influenced by the availability of substrates,
product inhibition,or alterations in the levels of allosteric
activators or inhibitors and by covalent modification of enzyme
(phosphorylated /dephosphorylated form)
• Activity of allosteric enzymes increase or decrease under the
influence of effector molecules.

BY:MUKESH DHITAL
B. Communication between cells (intercellular):
Gap junctions allow direct communication
between the cytoplasms of adjacent cells.
• For energy metabolism, the most important
route of communication is chemical signaling
between cells by bloodborne hormones or by
neurotransmitters

BY:MUKESH DHITAL
C.Second messenger systems /(Hormonal /neural
regulation)
• Second messenger system undergo the cascade of
events that translates hormone or neurotransmitter
binding into a cellular response.
• Two of the most widely recognized second
messenger systems are the calcium/
phosphatidylinositol system and the adenylyl cyclase
system, which is particularly important in regulating
the pathways of intermediary metabolism.
BY:MUKESH DHITAL
G-PROTEIN COUPLED RECEPTOR

BY:MUKESH DHITAL
BY:MUKESH DHITAL
BY:MUKESH DHITAL
D.Regulation at the DNA level-
-The concentration of the enzyme is changed
by regulation at the level of synthesis of the
enzyme. Eg.Induction and repression of
enzyme activity.
-Inducers stimulate enzyme synthesis wheras
end products repress enzyme synthesis.

BY:MUKESH DHITAL
 REGULATORY PRINCIPLES
• Let us consider a simple anabolic pathway in a
biosynthetic product such as heme ,cholesterol or a
purine is synthesized from a simple precursor.
• Substrate A B C D product E
• The pathway has to be active when the end product
E is needed.When there is already an oversupply of
product E ,on the other hand the pathway has to be
inhibited.
• In fact anabolic pathaways generally are inhibited by
high concentration of the end product.This principle
of regulation is called feedback inhibition.
BY:MUKESH DHITAL
WHICH ENZYME FOR REGULATION?
• Not all enzymes in a pathway are regulated.Short
term regulation,in particular,affects only one or a few
enzymes in the pathway.
• Essential features of regulatory enzyme:
1.It should serve an essential function in only one
metabolic pathway .
2.It has to catalyze the rate- limiting step.Which is the
slowest step and by inhibiting the catalytic efficiency
or reducing the quantity of the enzyme catalyzing
such a step, an immediate reduction in flux through
the entire pathway can be affected .This step is thus
also known as bottle neck point of the pathway.

BY:MUKESH DHITAL
• It should be the enzyme that catalyze one of the
committed irreversible steps in the pathway.
- Regulation of the committed step ensures that
only the substrate of the pathway accumulates
when the regulated enzyme is inhibited.If a later
reactions were regulated,one or more metabolic
intermediates would accumulate and possibly
cause toxic effects.

BY:MUKESH DHITAL
• In energy producing catabolic pathways the
important product is ATP .Therefore ATP is used
as feedback ihibitor.
• When ATP in short supply,the catabolic pathways
are stimulated, and when it is abundant they are
inhibited.
• ATP level is inversly related to the concentrations
of ADP and AMP .Thus ADP and AMP often act
opposite to ATP in the regulation of metabolic
pathways.
BY:MUKESH DHITAL
 METHODS OF REGULATION OF
REGULATORY ENZYMES
• One or more of the following mechanisms are
known to regulate the concentration of
regulatory enzyme in tissues:
1. Allosteric regulation
2. Reversible covalent modification
3.Regulation of enzyme synthesis and
degradation.
4.Proteolytic activation
BY:MUKESH DHITAL
 SPECIAL TYPE OF REGULATION
• In feedforward stimulation,a substrate
stimulates the pathway by which it is utilized
• The induction of lac operon of E.coli in the
presence of lactose is an example of
feedforward stimulation.

BY:MUKESH DHITAL
THANK YOU

BY:MUKESH DHITAL