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BCH 410 Lecture Note 1

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BCH 410 Lecture Note 1

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BCH 410

INORGANIC
BIOCHEMISTRY
Contents
❖ Ionic gradients

❖ Mineralization

❖ Blood clotting

❖ Metalloproteins containing Zn, Fe, Co, Cu and Mn


Ionic Gradients
❖ Ionic gradient is the concentration gradient of a particular ion.
▪ It is the difference of concentration of the ion between the two
sides of the plasma membrane.

❖ Ionic gradients are important in many biological processes,


such as cell membrane transport, neural signaling, oxidative
phosphorylation and photosynthesis.
Ionic Gradients Contd.
❖ Since the ions are charged, they cannot pass through
cellular membranes via simple diffusion.

❖ Two different mechanisms can transport the ions across the


membrane:
▪ (1) Passive transport
▪ (2) Active transport
Passive Transport of Ions
❖ In passive transport, molecule movement across the membrane is
determined by concentration and electrochemical gradients.

❖ In natural membranes, there are transmembrane channels, pore-like


structures composed of proteins that constitute selective ion channels
within the plasma membrane of nearly all cells and many intracellular
organelles.

❖ Ion channels provide actual holes through which the ions can diffuse
across the membrane; no binding takes place.
Passive Transport of Ions Contd.

❖ Thus, ions passively move through open channels in membranes


from the medium where their concentration is high to the
medium where their concentration is lower without the input (or
help) of metabolic energy.

❖ Examples include ungated, voltage-gated, ligand-gated,


mechanically-gated and temperature-gated ion channels.
Passive Transport of Ions Contd.
❖ 1. Ungated Ion Channels:
▪ A few are open all the time and thus are ungated.

▪ Cells tend to have some ungated K+ and ungated Cl- ion channels.

▪ On the other hand, two important ions, Na+ and Ca2+, do not have ungated ion channels, but only
move through gated ion channels.

❖ 2. Voltage-gated Ion Channels:


▪ Ion channels that open or close in response to changes in the membrane potential are termed
voltage-gated.

▪ Especially important are voltage-gated Na+, Ca2+, K+, and Cl- ion channels, which provide split
second regulation in the nervous system and in muscles.
Passive Transport of Ions Contd.
❖ 3. Ligand-gated Ion Channels:
▪ Many ion channels are ligand-gated; that is, they open in response to the binding of an
extracellular or intracellular regulatory molecule.

▪ An example is an ion channel for K+ that opens after the binding of ATP (an intracellular
ligand) from the cytosol. This ion channel plays a role in the secretion of insulin from the
pancreas.

❖ 4. Mechanically-gated Ion Channels:


▪ These are ion channels that open in response to mechanical movement of adjacent structures.

▪ In eukaryotes, two of the best known mechanosensitive ion channels are the potassium
channels TREK-1 and TRAAK, both of which are found in mammalian neurons.
Passive Transport of Ions Contd.
❖ 5. Temperature-gated Ion Channels:
▪ Some ion channels are temperature-gated.

▪ These are found in sensory neurons in the skin and mucous membranes and open with
either an increase in temperature or decrease in temperature. This, of course, leads to
the sensations of warm and cold.

▪ The most important is an ion channel that normally opens in response to noxious heat,
but that also responds to capsaicin, the substance that gives chili peppers their special
characteristic.
Active Transport of Ions
❖ In active transport of ions, the ions bind to the carrier proteins and are
transported against a concentration gradient when coupled to ATP hydrolysis as
a source of energy.

❖ Because energy is provided in this way, the transporter can move the substance
to a higher concentration. Thus, these transporters always move the transported
substance in one direction, regardless of the concentration gradient.

❖ The maintenance of electrochemical gradients in biologic systems is so


important that it consumes perhaps 30–40% of the total energy expenditure in a
cell.
Active Transport of Ions Contd.
❖In general, cells maintain a low intracellular Na+ concentration and a high intracellular
K+ concentration, along with a net negative electrical potential inside.
❖The transporter (pump) that maintains these gradients is an ATPase that is activated by
Na+ and K+ (Na+-K+ ATPase).
Active Transport of Ions Contd.
❖ The ATPase is an integral membrane protein and requires phospholipids
for activity.

❖ The ATPase has catalytic centers for both ATP and Na+ on the intracellular
(cytoplasmic) side of the membrane, but the K+ binding site is located on
the extracellular side of the membrane.

❖ Na+-K+ ATPase pump moves three Na+ ions from inside the cell to the
outside and bring two K+ ions from the outside to the inside for every
molecule of ATP hydrolyzed to ADP by the membrane-associated ATPase.
Active Transport of Ions Contd.
❖ Ouabain or digitalis inhibits this ATPase by binding to the extracellular
domain.

❖ Inhibition of the ATPase by ouabain can be antagonized by extracellular


K+.

❖ In addition, there are active transporters both for Ca2+ and for H+ found
in the stomach and participate in the secretion of acid into stomach.

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