4. Relationship between substrate concentration and the rate
of an enzyme-catalysed reaction
rectangular
hyperbola
Maximal velocity (Vmax)
Maximum reaction rate (v
observed at saturating
substrate
concentrations) for a given
concentration of enzyme:
Vmax=¼ kcat[E]t.
9. Inhibitors
Some substances reduce or even stop the catalytic activity of enzymes in
biochemical reactions. They block or distort the active site. These chemicals
are called inhibitors, because they inhibit reaction.
Inhibitors that occupy the active site and prevent a substrate molecule from
binding to the enzyme are said to be active site-directed (or competitive, as
they 'compete' with the substrate for the active site).
Inhibitors that attach to other parts of the enzyme molecule, perhaps
distorting its shape, are said to be non-active site-directed (or non
competitive)
10. Reversible and irreversible inhibitors are chemicals which bind to an
enzyme to suppress its activity. One method to accomplish this is to almost
permanently bind to an enzyme. These types of inhibitors are called
irreversible. However, other chemicals can transiently bind to an enzyme.
These are called reversible. Reversible inhibitors either bind to an active site
(competitive inhibitors), or to another site on the enzyme (non-competitive
inhibitors). (TeachMe Physiology, 2022)
_____________________________________________
TeachMe Physiology, 2022. Enzyme Inhibition
https://teachmephysiology.com/biochemistry/molecules-and-signalling/enzyme-inhibition/
11. Competitive Inhibition
During C I , The inhibitor (I) competes with the substrate (S) for the
enzyme active site (also known as the S-binding site). Binding of either of
these molecules in the active site is a mutually exclusive event.
• The substrate and inhibitor share a high degree of structural similarity.
However, the inhibitor cannot proceed through the reaction to produce
product.
• Increasing the concentration of substrate will outcompete the inhibitor for
binding to the enzyme active site
• A competitive reversible inhibitor can be identified by its characteristic
effects upon kinetic data
12. Competitive Inhibition
Competitive inhibitors compete with the substrate at the active site, and
therefore increase Km (the Michaelis-Menten constant). However, Vmax is
unchanged because, with enough substrate concentration, the reaction can
still complete. The graph plot of enzyme activity against substrate
concentration would be shifted to the right due to the increase of the Km,
whilst the Lineweaver-Burke plot would be steeper when compared with
no inhibitor.
15. Competitive Inhibition
Inhibitor resembles the substrate and thus competes with it for the
binding site at the active center of the enzyme. Inhibitor binds at the
active center, blocking the substrate from interacting with the binding
site.
Inhibitor can be overcome through an excess of the substrate
; therefore, this inhibition is reversible.
Decreases affinity of the enzyme for the substrate
As affinity decreases, the Km value increases, since an increased
Substrate concentration is required to obtain the half-maximal velocity.
Vmax is not changed, however. ( Lecturio,2022)
_____________________________________________
Lecturio, 2022
https://www.lecturio.com/concepts/enzyme-inhibition/
19. Competitive inhibition is usually caused by substances that are structurally
related to the substrate, and thus combine at the same binding site as the
substrate. The bindings are exclusive to each other, forming either an
enzyme–substrate (ES) or an enzyme–inhibitor (EI) complex but not a
ternary complex (EIS)
This type of inhibition can be completely overcome by high substrate
concentrations and thus does not affect the V. The Km is increased by a
factor of (1 + [I]/Ki). (Pharmacology, 2009)
______________________________________
Pharmacology, 2009. Competitive Inhibition.
https://www.sciencedirect.com/topics/medicine-and-dentistry/competitive-inhibition
Hyone-Myong Eun, in Enzymology Primer for Recombinant DNA Technology, 1996
20. ______________________________________
Pharmacology, 2009. Competitive Inhibition.
https://www.sciencedirect.com/topics/medicine-and-dentistry/competitive-inhibition
Hyone-Myong Eun, in Enzymology Primer for Recombinant DNA Technology, 1996
John W. Pelley, in Elsevier's Integrated Review Biochemistry (Second Edition), 2012
An example of a competitive inhibitor is the
antineoplastic drug methotrexate. Methotrexate
has a structure similar to that of the vitamin folic
acid. It acts by inhibiting the enzyme
dihydrofolate reductase, preventing the
regeneration of dihydrofolate from
tetrahydrofolate. This interferes with DNA
synthesis and blocks cell division in rapidly
dividing cancer cells.
