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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.
Explain how cholesterol is taken up by animal cells, such as human cells, and
how cholesterol contributes to the formation of atherosclerotic plaques.
Cholesterol is important for cell membrane assembly (phospholipid bilayer) and also
metabolic processes (steroid metabolism). Cholesterol is synthesized by liver but its
hydrophobic property prevents it from being transported in blood freely. Instead, it is
carried as low density lipoprotein (LDL) particles. They carry cholesterol in the blood
from the liver, where it’s made, to the body’s cells. LDL consists of a central core of
cholesterol esterified to chains of fatty acids, surrounded by a coat of phospholipids and
unesterified cholesterol and a single molecule of apolipoprotein B, which interacts with
the LDL receptors. Cells contain a number of LDL receptors on the membrane. When
LDL binds to the receptors, a coated vesicle forms and delivers the LDL to the
lysosome, where it is digested. The protein of LDL is digested and cholesterol is
released. High levels of LDL is associated with an increased risk of heart disease, for
example, atherosclerosis. This is characterized by LDL-containing plaques
(atherosclerotic plaques), which form on the inner walls of blood vessels (in with
endothelial cells). This causes the narrowing of major arteries and reduced blood flow.
These plaques also act as sites for formation of blood clots, which block coronary
arteries and can lead to heart attacks. Plaque formation is initiated by injury to the
endothelial cells lining the blood vessels, which attracts macrophages. They ingest the
LDL, which accumulates in cholesterol droplets in the cytoplasm. This causes the
smooth muscle cells around the blood vessels to proliferate and produce a fibrous cap
that bulges into the arterial lumen.