Class Notes (1,100,000)
CA (630,000)
McGill (30,000)
BIOL (600)
BIOL 200 (400)
Lecture 9

BIOL 200 Lecture Notes - Lecture 9: Oxidative Phosphorylation, Neurotoxicity, Physostigmine

Biology (Sci)
Course Code
BIOL 200
Mathieu Roy

This preview shows half of the first page. to view the full 2 pages of the document.
Many antibiotics such as penicillin and vancomycin inhibit the enzymes that produce and then
cross-link the strands of this polymer together. This causes the cell wall to lose strength and the
bacteria to burst. In the figure, a molecule of penicillin (shown in a ball-and-stick form) is shown
bound to its target, thetranspeptidase from the bacteria Streptomyces R61 (the protein is shown
as a ribbon-diagram).Drug design is facilitated when an enzyme that is essential to the pathogen's
survival is absent or very different in humans. In the example above, humans do not make
peptidoglycan, therefore inhibitors of this process are selectively toxic to bacteria. Selective
toxicity is also produced in antibiotics by exploiting differences in the structure of
the ribosomes in bacteria, or how they make fatty acids.Enzyme inhibitors are also important in
metabolic control. Many metabolic pathways in the cell are inhibited by metabolitesthat control
enzyme activity through allosteric regulation or substrate inhibition. A good example is the
allosteric regulation of the glycolytic pathway. This catabolic pathway consumes glucose and
produces ATP, NADH and pyruvate. A key step for the regulation of glycolysis is an early
reaction in the pathway catalysed by phosphofructokinase-1 (PFK1). When ATP levels rise, ATP
binds an allosteric site in PFK1 to decrease the rate of the enzyme reaction; glycolysis is
inhibited and ATP production falls. This negative feedback control helps maintain a steady
concentration of ATP in the cell. However, metabolic pathways are not just regulated through
inhibition since enzyme activation is equally important. With respect to PFK1,fructose 2,6-
bisphosphate and ADP are examples of metabolites that are allosteric activators.
Physiological enzyme inhibition can also be produced by specific protein inhibitors. This
mechanism occurs in the pancreas, which synthesises many digestive precursor enzymes known
as zymogens. Many of these are activated by the trypsinprotease, so it is important to inhibit the
activity of trypsin in the pancreas to prevent the organ from digesting itself. One way in which
the activity of trypsin is controlled is the production of a specific and potent trypsin
inhibitor protein in the pancreas. This inhibitor binds tightly to trypsin, preventing the trypsin
activity that would otherwise be detrimental to the organ. Although the trypsin inhibitor is a
protein, it avoids being hydrolysed as a substrate by the protease by excluding water from
trypsin's active site and destabilising the transition state. Other examples of physiological
enzyme inhibitor proteins include the barstar inhibitor of the bacterial ribonuclease barnase and
the inhibitors of protein phosphatasesMany herbicides and pesticides are enzyme
inhibitors. Acetylcholinesterase (AChE) is an enzyme found in animals from insects to humans.
It is essential to nerve cell function through its mechanism of breaking down the
neurotransmitteracetylcholine into its constituents, acetate and choline. This is somewhat unique
among neurotransmitters as most, including serotonin, dopamine, and norepinephrine, are
absorbed from the synaptic cleft rather than cleaved. A large number of AChE inhibitors are used
in both medicine and agriculture. Reversible competitive inhibitors, such
as edrophonium,physostigmine, and neostigmine, are used in the treatment of myasthenia
gravis and in anaesthesia. The carbamatepesticides are also examples of reversible AChE
inhibitors. The organophosphate insecticides such as malathion, parathion,
and chlorpyrifos irreversibly inhibit acetylcholinesterase.
The herbicide glyphosate is an inhibitor of 3-phosphoshikimate 1-carboxyvinyltransferase, other
herbicides, such as the sulfonylureas inhibit the enzyme acetolactate synthase. Both these
enzymes are needed for plants to make branched-chainamino acids. Many other enzymess are
inhibited by herbicides, including enzymes needed for the biosynthesis
of lipids andcarotenoids and the processes of photosynthesis and oxidative phosphorylation.
You're Reading a Preview

Unlock to view full version