Medicinal Chemistry

(Jacob Rumans) #1

The composition of the cell membrane varies from one anatomical location to
another. For example, the cell membranes of neurons are 75% lipid and 25% protein,
while those of epithelial cells in the intestinal villi are 75% protein and 25% lipid. The
mixture of lipids that constitutes the cell membranes of neurons is different from that
found in other organ systems; the same applies to the membrane proteins of neurons.
Cell membranes are dynamic structures: the phospholipids and fatty acids are in a state
of constant turnover; the protein components tend to turnover with a cycle ranging from
9 days to 6 months.
Thecytoplasmis the semi-fluid polyphasic colloid that comprises the bulk of the
cell’s interior between the cell membrane and the nucleus; it contains enzymes respon-
sible for catalyzing the biosynthetic machinery of the cell and organellesresponsible
for specific tasks within the cell. Cytoplasm must be differentiated from protoplasm;
protoplasm is the whole material contained within the cell membrane and is further dif-
ferentiated into the material found within the nucleus (nucleoplasm) and material exter-
nal to the nucleus (cytoplasm). Organelles are important functional structures within the
cytoplasm. Various structures visible by light microscopy are classified as organelles,
including mitochondria, endoplasmic reticulum, and lysosomes.
Mitochondria are rod-like organelles, 400 μm in length, with a smooth outer mem-
brane and an inner membrane folded into projections called cristae. Mitochondria are
enzyme-rich organelles which produce adenosine triphosphate (ATP) and function as
the energy source of the cell. The endoplasmic reticulum (ER) is a complex system of
fluid-filled tubes with membranes similar to the cell membrane. The ER permeates all
parts of the cytoplasm. There are two types of endoplasmic reticulum:rough endoplas-
mic reticulum(RER) and smooth endoplasmic reticulum (SER).RER is made “rough”
by being studded with ribosomes, which are small granular particles that are the site of
protein synthesis. SER has many functions, including being the site of lipid and steroid
biosynthesis. The Golgi apparatus is a specialized portion of the ER composed of
flattened sacs and used in the packaging of substances for secretion. Lysosomes are
membrane-bound sacs of hydrolytic enzymes whose function within the cytoplasm is
to engulf and digest foreign substances entering the cell. Under certain circumstances
the lysosome can be suicidal for the cell, causing autodigestion of the cell following
release of its hydrolytic enzymes. In fact, certain venoms, such as cobra venom from
theAfrican Rhingal, destroy cells by “turning on” lysosomes to release their enzymes.
Proteinaceous rods, 4–5 nm thick, are found in the cytoplasm of most cells, especially
muscle cells, providing rigidity, support, and participating in contractility processes;
these rods are called fibrils. In certain places these fibrils come together to form tubu-
lar assemblies, called microtubules, which are involved in cellular transport and motion.
The final principal component of the cell is the nucleus. This is located in the center
of the cell and is surrounded by a double membrane, the outer layer being derived from
the ER of the cytoplasm and the inner layer coming from the nucleus itself. The two
leaflets of the double membrane are fused in places, producing nuclear pores that
enable the transfer of macromolecules from the cytoplasm to the nucleus. Two impor-
tant components of the nucleus are chromatin and the nucleolus.Chromatin represents
polymers of DNA complexed with protein. The nucleolus is a complex substructure,
composed of ribonucleoprotein granules, that controls the synthesis of RNA destined to
form the ribosomes of the cytoplasm. Cells engaged heavily in protein synthesis have


408 MEDICINAL CHEMISTRY

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