Adenosine membrane of proxima, tubule epithelial cells of

Triphosphate Binding Cassette (ABC) Transporter:

The human adenosine triphosphate binding cassete (ABC) has
seven subfamilies that contain 48 members. It is present in all the living
organisms from human to microorganisms, ABC transporter can function as influx
or efflux. ABC transporter is a membrane protein that have the ability to bind
and hydrolyze the ATP and use it as a source of energy to efflux the substrate
out of the cell. This transporter only requires energy to efflux the substance out.
In the influx procedure the substrate is passively transported to the cell with
no need for energy. ABC transporter has an important role in regulating the
absorption, distribution, metabolism and excretion of cellular lipid and
glucose, it controls the glucose and lipid metabolism by regulate the secretion
and activation of insulin hormone and lipase enzyme.

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The Structure
of ABC Transporter:

The figure below shows the ABC transporter structure which consists
of four domains, two of them are the binding site, they are called trance
membrane domains, the trance membrane domains are taking place in the cell
membrane. The other two are the ATP binding domains which are called nucleotide
binding domains, they are taking place in the cytoplasm. The trance membrane
domains bind to the substrate and the nucleotide biding domains binds to the
ATP molecule.



binding domain

membrane domain






Triphosphate Binding Cassette B1 (ABCB1):

ATP binding cassette B1 (ABCB1) transporter comes from the
ATP binding cassette subfamily B member one. It can be classified based on the structure
of the polypeptide chain to full and half transporter. If the transporter is
composed of one linked polypeptide chain, it’s called full transporter, otherwise,
if the transporter is present in two separated polypeptide chain then it’s
called half transporter. The transporter uses the energy of ATP hydrolysis to
establish a direct membrane movement which creates a pocket like structure used
to transport the substrate across the membrane. In the abnormal condition ABCB1
transporter is responsible for giving the cancer cells it’s multidrug resistant
(MDR1) property, in this case the transporter can be named as permeability glycoprotein
(p-gp). ABCB1 transporter is present in the brush border membrane of the
intestinal cells, biliary canalicular membrane of hepatocyte, luminal membrane
of proxima, tubule epithelial cells of the kidney and endothelial cells of
blood brain barrier.

Function of

The main function of ATP binding cassette B1 (ABCB1) is to
protect the cell by pumping the toxic component or metabolite out of the cell which
help in decreasing the cell exposure to the toxic molecules or xenobiotic, as a
result it limits the entry of the xenobiotic to the cell. it works in decreasing
the drug bioavailability by excreting the drug from the body by the excretion organs
like in the intestine epithelial cell where it pumps the drug to the intestinal
lumen and in the liver where it pumps the drug to the bile duct. ABCB1 protect
the organs by decreasing the exposure of the cell to the toxic xenobiotic like
in blood brain barrier, testes and placenta. This transporter is characterized
by its high transporter capacity and its various wide substrate recognition.

When ABCB1 transporter is over expressed, it causes
multidrug resistance(MDR) which is responsible for making the resistance of
drugs in the cancer cells. Permeability glycoprotein (p-gp) is a glycoprotein
encoded by the ABCB1 transporter. It works in pumping the drugs to outside the cell
which makes the drug concentration inside the cell much lower than the outside,
as a result it protects the cancer cell from the anticancer drugs. 


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