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16 Oct 2011
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Describe how the proton-motive force is set up and how interfering with the
proton-motive force was the focus of an early unsuccessful diet pill?
There are 2 components to the proton gradient, which is built across the inner
mitochondrial membrane during the electron transport chain. There is the pH gradient (a
chemical gradient) and a voltage gradient (an electrical gradient). As a result, this is an
electrochemical gradient. The proton-motive force is the expression of energy present in
the electrochemical gradient. This value is approximately 220 millivolts. The voltage
component is around 80% and the pH component is around 20%. The inner
mitochondrial membrane must be maintained so that it is highly impermeable to H+.
However, 2,4-dinitrophenol (DNP), uncouples the ETC from ATP formation. It makes the
inner mitochondrial membrane permeable to H+. Protons would travel across the inner
mitochondrial membrane, but no ATP would be produced. DNP was used in the 1920`s
as a diet pill. It collapses the proton-motive force and instead of producing ATP, the
energy is lost as heat. To try and maintain normal ATP levels, cells start to burn fat.
However, due to deaths, the drug was no longer used.
What mechanisms do professional phagocytes have to kill bacteria and how do
some bacteria get around them?
Phagocytosis is basically “cell eating”. Some cells are specialized in the uptake of larger
particles from the environment into the cell itself. In the cell, the particle is transported
via a phagosome to a lysosome, which is the cell’s digestive organelle made from golgi
bodies. The phagosome then fuses with a primary lysosome to form a secondary
lysosome. This fusion activates lysosomal enzymes. There are around 50 different
hydrolytic enzymes in lysosomes. The digested contents can provide nutrition, where
the contents are moved to the cytoplasm. However, phagocytosis is also used as
defense against microorganisms. Animals possess professional phagocytes called
macrophages and neutrophils. These phagocytes have special mechanisms for killing
microorganisms. The lysosomes contain an enzyme called lysozyme that degrades the
cell walls of bacteria. The lysosome also has an acidic pH that kills some bacteria. In
addition, oxygen free radicals can be generated in a phagosome to kill bacteria.
However, not all bacteria can be destroyed. For example, Mycobacterium tuberculosis,
which causes tuberculosis, prevents the fusion of the primary lysosome and phagosome
to form a secondary lysosome. The phagosome containing the bacteria is not
recognized by the primary lysosome and as a result, the bacteria are able to remain
dormant in the cell. Another example is Coxiella burnetii, which cause Q fever. This
bacteria is resistant to the lysosomal enzymes and also the acidic pH. Also, meningitis,
caused by Listeria monocytogenes, produce proteins that destroy the integrity of the
lysosomal membrane, allowing the bacteria to escape into the cytoplasm. There, they
feed off the nutrients, which are meant for the macrophage.
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