GROUP# 02

REGULATION OF AREEJ ZAFAR ANZA IFTIKHAR

AYESHA GHAFOOR JAWERIA MUMTAZ
GLYCOLYSIS MAHAM QAISER Aimen BiBi
PRESENTED TO; Dr. TEHSEEN
Regulation of Glycolytic Pathway

A general rule of thumb for metabolic regulation is A committed step is one in which the substrate has only
that pathways are regulated in the first step. one path. Because glycolytic intermediates are fed into
several additional pathways, the regulation of glycolysis
occurs at more than one point.
Free energy diagram
of glycolysis
The free energy change depends on two
factors:
• The free energy difference between the
products and reactants in the standard
state, and the concentration of the
products and reactants. In the figure, the
standard free energies and
concentrations were used to calculate
the total free energy differences
between products and reactants at each
step.
• Reactions at equilibrium have a free
energy change of zero.
 HEXOKINASE
REGULATORY
ENZYMES
PHOSPHOFRUKTO
KINASE-1

Pyruvate
KINASE
In three enzyme-
catalyzed reactions:

• 1. Formation of glucose-6-phosphate.
The entry point for glucose is the
formation of glucose-6-phosphate.
Hexokinase is feedback inhibited by its
product, so glucose phosphorylation is
inhibited if glucose‐6‐phosphate
accumulates. In mammalian cells,
glycogen breakdown is regulated by
covalent modification of glycogen
phosphorylase. This regulation reduces
the rate of glucose-6-phosphate
formation.
ALLOSTERIC
ENZYMES
 They change their confirmation upon
binding of an effector to an active
binding
 site called allosteric site

 This change in confirmation

 is called as covalent modification

 The effector effects catalytic activity

 of enzyme. Effect can be positive or

negative
ACTIVATORS
• Enzyme activators are molecules that bind to enzymes and
increase their activity.
• Positive effectors
INHIBITORS

 Enzyme inhibitors can be defined as

molecules that bind to enzymes and
decrease their activity.
•2.Fructose-6-phosphate→ fructose-1,6-
bisphosphate.
• Glucose‐6‐phosphate has other metabolic fates
than just leading to pyruvate.

•The most important regulatory step of glycolysis is

the phosphofructokinase reaction.
PHOSPHOFRUCTOKI
NASE-1 (PFK-1)
An allosteric regulatory enzyme. It converts fructose-6-phosphate to
froctose-1,6-bisphosphate
 ALLOSTERIC INHIBITORS

 1-ATP

High level ATP in cell indicates no need of glycolysis for energy as ATP
is already present in excess.so ATP inhibits PFK-1 action.
 2-citrate

An intermediate of TCA cycle where 2 carbon enter the cycle .high level
of citrate indicates an abundant supply of intermediate for energy
production .so inhibits function of PFK-1 for glycolysis.
 AMP

High AMP level in the cell, e. show ATP levels are low and required to
the cell. Thus AMP binds with allosteric PFK-1 enzyme and activates the
enzyme, AMP is positively regulating this enzyme . Glycolysis is
regulated as a result and energy is produced.Fructose-2,6-bisphosphateIt
is produced from PFK-2. It also positively regulate glycolysis
3.Phosphoenolpyruvate → pyruvate.
• The third major step in the free energy
diagram is the pyruvate kinase
reaction, where ATP is formed from
phosphoenolpyruvate. ATP inhibits
pyruvate kinase, similar to inhibition of
PFK.
• Pyruvate kinase is also inhibited by
acetyl‐coenzyme A, a product of pyruvate
metabolism that enters the TCA cycle.
Fatty acids also allosterically inhibit
pyruvate kinase, which serves as an
indicator that alternative energy sources
are available to the cell.
• Pyruvate kinase is also activated by
fructose-1,6-bisphosphate.