METABOLIC CONTROL

& REGULATION
Bhaskar Ganguly
Ph.D., M.V.Sc., B.V.Sc. & A.H.

Irreversible Thermodynamics
If the change from initial state to final state is
so slow that process can be assumed to be
proceeding through a series of closely
spaced quasi-equilibrium states then such a
process is called reversible process and the
entire path of time evolution of each of the
state variables can be obtained from the
conventional theory of thermodynamics.
All the processes that we are interested in
are irreversible processes and hence most of
the time system is not in an equilibrium state
as system evolves in time.

Regulation of Metabolic flux

1.
2.
3.
4.

Nutrient supply
Nutrient transport
Enzyme amount
Product need

5.
6.
7.
8.

Feedback control
Endocrine control
Neural control
Cofactor availability

Regulation of Metabolic flux

Nutrient supply:
Metabolic sequences tend to adapt quantitatively to
the supply of a nutrient. The absence of the
substrate may also lead to a lack of its enzyme. E.g.
Lac operon

Nutrient transport:
Supply of a nutrient (or substrate) into a cell can be
regulated by controlling the transport of the nutrient
across the cell membrane. E.g. insulin and glucose

Enzyme amount:
Induction/ Repression E.g. insulin and glucocorticoids
Allosteric effects
Inhibitors

Regulation of Metabolic flux

Product need:
Demand of a metabolic product may stimulate its
increased output. E.g. stimulation of hepatic
glycogenolysis by a low blood sugar

Feedback control:
The major mechanism for the regulation of metabolic
pathways. E.g. Inhibition of porphyrin heme
biosynthesis by the end product heme (aminolevulinic acid synthetase).

Endocrine control:
Conversion of inactive form to the active form
Regulation of transport through the cell membrane
Enzyme induction and repression

Regulation of Metabolic flux

Neural control:
Indirect action by hormonal or other mechanisms.

Cofactor availability
The enzyme-catalyzed reactions, requiring a cofactor,
are affected by the amount of the cofactor available.
E.g. Large amount of NAD+ is required for the
metabolism of ethanol; lesser NAD+ may then be
available for other metabolic pathways requiring
NAD+ as cofactor while requiring NADH2 may be
stimulated.

Short term and Long term

Controls

Short term Controls

Exerted post-translationally, i.e. on the

protein; Involve reversible mechanisms that
are temporary in nature; phosphorylation/ dephosphorylation,
receptor
inactivation,
enzyme
sequestration,
feedback
mechanisms,
activators
and
inhibitors,
second messengers, etc.

Long term Controls

Regulation at the level of genetic expression,
mostly at the transcriptional level i.e. before
protein formation. Involve gene condensation
and inactivation, inducers and repressors,

Thank you