A basic knowledge of aquaporins. Aquaporin are channel proteins that allow the passive diffusion of water through them.Aquaporins are membrane water channels that play critical roles in controlling the water contents of cells. These channels are widely distributed in all kingdoms of life, including bacteria, plants, and mammals. In 2003 Nobel Prize in Chemistry was awarded to Peter Agre "for the discovery of water channels". More than ten different aquaporin have been found in human body AQPs can be divided into three subfamilies: Orthodox or classical aquaporin, considered to be water selective. Aqua-glyceroporin, permeable to glycerol and other small solutes in addition to water. S-aquaporin, also called unorthodox super-aquaporin or subcellular aquaporin, a third subfamily only present in animals but not in plants, fungi and bacteria with permeability still uncertain.

1. AQUAPORIN IS A
CHANNEL PROTEIN

2. DEFINITION
Aquaporins are membrane water channels that play critical roles in
controlling the water contents of cells.
 These channels are widely distributed in all kingdoms of life, including
bacteria, plants, and mammals.
HISTORY OF AQUAPORINS
In 1988, Agre and coworkers isolated a new protein from the RBC
membrane and renal proximal tubule membranes in Xenopus oocytes and
nick-named CHIP28 (channel-forming integral membrane protein of 28
kDa).
Only in 1992 Agre's group suggested that "it is likely that CHIP28 is a
functional unit of membrane water channels“ and were first given the name
as Aquaporin-1.
In 2003 Nobel Prize in Chemistry was awarded to Peter Agre "for the
discovery of water channels",
AQUAPORINS

5. IMPORTANCE OF WATER
• Cell life
• Chemical and metabolic
reactions
• Transport of nutrients and
removal of waste
• Body temperature regulation
• As a lubricant.

6. Polar molecule has a net dipole as a result of the
opposing charges (i.e. having a partial positive
and partial negative charges ) from polar bonds
arrange asymmetrically. Water is an example of a
polar molecule since it has a slight +ve charge on
hydrogen atom and slight –ve charge on the
oxygen atom.
NEED FOR AN AQUAPORIN
WATER IS A POLAR MOLECULE

7. As the diffusion of water molecules through
hydrophobic plasma membrane is a very slow
process and which is not fast enough to keep our
cells alive and to regulate all the essential
functions of the body . Therefore we need a
channel that could allow a much faster transport
of water across membranes relative to lipid
bilayer. A single human aquaporin-1 channel
facilitates water transport at a rate of roughly 3
billion water molecules per second.
Cont…

8.  More than ten different aquaporin have been found in human
body
 AQPs can be divided into three subfamilies:
 Orthodox or classical aquaporin, considered to be water
selective.
 Aqua-glyceroporin, permeable to glycerol and other small
solutes in addition to water.
 S-aquaporin, also called unorthodox super-aquaporin or
subcellular aquaporin, a third subfamily only present in animals
but not in plants, fungi and bacteria with permeability still
uncertain.
TYPES OF AQUAPORINS

9. Aquaporin proteins are composed of a bundle of
six transmembrane α-helices. They are
embedded in the cell membrane. The amino and
carboxyl ends face the inside of the cell.
Between the helices are five regions (A – E) that
loop into or out of the cell membrane, two of
them hydrophobic (B, E), with an asparagine–
proline–alanine ("NPA motif") pattern.
STRUCTURE OF
AQUAPORIN

12.  The asparagine-prolin-alanine sequences (NPA motifs)
are highly conserved in aquaporin water channel
family. Studies of AQP1 structure demonstrated that
the two NPA motifs are in the narrow central
constriction of the channel, serving to bind water
molecules for selective and efficient water passage.
 Orientation of water molecules moving through the
channel assures that only water passes between cells
due to the single line passage of molecule.
 They create a distinctive hourglass shape, making the
water channel narrow in the middle and wider at each
end.
 The oxygen in each water molecule faces forwards as it
enters, turning around half way along and leaving with
the oxygen facing backwards. Why this rotation occurs
is not entirely clear yet.
NPA MOTIFS

15.  The aromatic/arginine or "ar/R" selectivity filter is a cluster
of amino acids that help bind to water molecules and exclude
other molecules that may try to enter the pore. It is the
mechanism by which the aquaporin is able to selectively bind
water molecules (hence allowing them through) and prevent
other molecules from entering.
 it is typically the tightest part of the channel. Its narrowness
weakens the hydrogen bonds between water molecules,
enabling the arginine, which carry a positive charge, to
interact with the water molecules and to filter out undesirable
protons.
"AR/R" SELECTIVITY
FILTER

16.  The most remarkable feature of aquaporin channels is their high
selectivity and efficiency on water or glycerol permeation,
excluding ions, and protons .
 Apart from water and glycerol, a number of other permeants
(substances which pass though membrane) such as urea,
ammonia, hydrogen peroxide, carbon dioxide, metalloids, nitric
oxide, and even ions were reported to permeate specific
aquaporin, although the mechanism of permeation is still not
understood.
PROPERTIES OF AQUAPORIN
Selectivity of aquaporin

17. Aquaporin are composed of different amino
acids that lined the structure of integral
protein.
One of such amino acids is arginine.
 This arginine bears a strong positive charge,
thus serving to repel protonated water (H3O+)/
protons.
How do aquaporin eliminate the
passage of protons?

20.  Maintaining proton gradients across cellular membranes is
essential for the bioenergetics of any living cell, as the resulting
proton motive force drives numerous transport processes,
membrane fusion, and ATP synthesis.
 Synthesis of ATP is driven by the electro-chemical trans
membrane potential associated with the proton gradient, either
across the inner mitochondrial membrane in eukaryotes, the
thylakoid membrane of chloroplasts in plants, or across the cell
membrane in bacteria.
 Accordingly, leakage of protons across biological membranes
would therefore be fatal to the cell.
ADVANTAGE OF
SELECTIVITY

21. OTHER IMPORTANT FEATURES OF AQUAPORIN
GATING OF AQUAPORIN
As the movement of water molecules is bidirectional,
so the water molecules can also travel from inside of
the cell to outside environment depending upon the
osmotic gradient.
• The gating of aquaporin is necessary to keep cells
hydrated during periods of drought. The
mechanism in some aquaporin involves the de-
phosphorylation of certain serine residues, causing
the protein to change shape. This change in shape
causes the tunnel of the protein to close and not
allow any water to pass through.

22. TRANSPORT OF GLYCEROL
Aqua-glyceroporin are involved in
skin hydration, cell proliferation,
carcinogenesis and fat metabolism.
Glycerol permeability in membranes
from various tissues and organs has
a key role in the regulation of
metabolic and energy homeostasis,
with the adipose tissue having a
pivotal role.

23.  Aquaporin channels are present in different cells of mammals.
One of this Aquaporin channel is present in kidney. In kidney
the reabsorption of water in collecting duct is done by
Aquaporin channels. It absorb more or less of water according
to the need.
 So, how this aquaporin channel regulate that at this time they
have to absorb more or less water it regulated by ADH(anti-
diuretic hormone)
 ADH also called vasopressin . It is hormone secreted by
hypothalamus in the brain and stored in the posterior pituitary
gland. It tells your kidney how much water to conserve.
 ADH constantly regulates and balances the amount of water in
your blood.
AQUAPORIN IN
MAMMALS

24. Aquaporin channel in mammals