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Toxicology
Roll no MZ.19.62
Assingment No 1
A fundamental question in biology is: How do substances get into and out of
a cell?
Since the cell is the ultimate level at which toxicants have their impact, the
answer to this question is relevant: not only for toxicants, but also for
substances needed for cell survival, such as nutrients(glucose), gases (O2,
CO2), electrolytes(Na+, K+, Cl-), and molecules produced by the cell for
export (enzymes, hormones, structural proteins).A knowledge of the
structure of epithelial cells, particularly the characteristics of the cell
membrane, or plasma membrane ,is important when considering why some
toxicants move through the barrier with relative ease while other toxicants
find entrance into the body difficult or impossible. The cell membrane is
composed of phospholipid molecules . As the term phospholipid implies,
there are two components to the molecule: phosphates and lipids. The
phosphate head is a region that is hydrophilic. This means that this portion
of the molecule prefers associating with water (hydro-, water; -philic,
attraction for or love of). In contrast, the lipid tail is a hydrophobic region,
which is repelled by water. Additionally, this region is said to be lipophilic,
or attractive to lipid-soluble substances. The cell membrane is like a
sandwich, composed of two layers of phospholipid molecules. A typical cell
membrane isabout 10 nm (10 one-billionths of a meter thick. The term
phospholipid bilayer provides a good description of the appearance of the
“sandwich.” In the middle of the phospholipid bilayer is a region where
adjacent lipid tails are located. The phosphate heads are found on the inner
an douter surfaces of the cell membrane where these regions are exposed to
water, the ubiquitous solvent found in living organisms.
The phospholipid bilayer forms as emipermeable membrane that surrounds
the cell. The membrane is termed semipermeable
since it permits some molecules to move across, while at the same time
stopping or impeding the progress of other molecules.
Process of Cellular Absorption
Substances use a number of different passive (spontaneous) and active
(energy-requiring) transport mechanisms to gain entrance into a cell. The
most commonly used process is simple diffusion. In this process the
molecule relies on its concentration gradient to enter the cell. This process is
passive, as opposed to active, since no cellular energy is used to “power” the
toxicant across the cell membrane. Remember, diffusion is the movement of
a substance (in this case a toxicant) from a region of high concentration into
a region of low concentration and, depending on the direction of the
concentration gradient, substances will continue to move into or out of a cell
until equilibrium is reached. In the absence of a concentration
gradient, no net movement of substances will occur. A second process used
to cross the cell membrane is facilitated diffusion. In this process molecules
become bound to specific carrier proteins found on the outer surface of the
cell membrane. The molecule is then passed, or passively transported, by the
membrane protein into the cell. The “energy” for transport is derived from
the potential energy stored in the concentration gradient, not from cell
energy input.
Facilitated diffusion is a well-known mechanism in the transport of
nutrients, such as glucose, across the cell membrane.
Facilitated diffusion is thought to play only a minor role in the transport of
toxicants into the cell; however, it does serve as an important transport
mechanism for the elimination of toxicants or their metabolites from the cell
following absorption
via other mechanisms.
Third, active transport, as a means to enter the cell, involves the
consumption of cellularly -produced energy, such as adenosine triphosphate
(ATP). Whereas passive and facilitated diffusion make good use of
concentration gradients, active transport enables the cell to transport
molecules against, or up, their concentration gradient. Although not a major
route of toxicant entry into the cell, active transport, like facilitated
diffusion, does play a vital role in the elimination of toxicants or their
metabolic intermediates from a cell. It is impossible for many large
molecules and particulates to go into or leave the cell via passive or active
transport mechanisms. Instead, these macromolecules enter and exit the cell
by two different processes called endocytosis and exocytosis, respectively.
During endocytosis the cell membrane will flow around
and engulf the macromolecules that are in close proximity to the cell. Once
engulfed, the paniculate , now with its cell
membrane covering, will invaginate or turn inward to form a vesicle. The
vesicle will detach from the adjacent cell membrane and become part of the
cytoplasm. Phagocytosis (cellular eating) and pinocytosis (cellular drinking)
are two types
of endocytosis. Phagocytosis, performed by special white blood cells, is
responsible for removing particulates from the small sacs (alveoli) in the
lung.