Biological Role of Na-K

Essential elements in warm blooded animals:

26 elements

Classification according to their properties

1.Alkaline and alkaline earth metals- 4: Na, K, Ca, Mg
2. Trace metals-10: Fe, Cu, Mn, Zn, Co, Mo, Cr, W, V, Ni
3. Non-metals-12: H, C,0, N, F, CI, 1, B, P, S, Se, Si

OClassification based on their requirements:

i. Macronutrients-13 elements that are required in relatively
large quantity. C, H, N, O, Na, K, Mg. Ca, S, P, CI, Si, Fe
ii. Micronutrients-13 elements that are required in relatively
small amounts in some forms of life. V, Cr, Mn, Zn, Cu,
N, Co, Mo, W, Se, F, LB
 Roles of metal ions in biological systems are
broadly classified as-
1. Regulatory action: K, Na, Ca, Mg, sends signals that tun
metabolic reactions on and oft.
2 Structural role: bones and teeth are formed by Ca, Zn
Electron transfer chemistry: Fe, Cu
4. Metal bonded metalloenzymes or coenzymes that catalyze
the enzymatic reactions.
5. Oxygen carriers-
Hemoglobin-Fe, is found in mammals;
Hemerythrine Fe, is found in marine invertibrates and
Hemocyanins-Cu, is found in orthopodas, molauses.
 Functions of Cell:
1. Encrgy Production from foods,
2. Create a nerve impulsc; maintaining an clectric potential
differencebetween extra and intra cellular fluid-Role of
alkaline metal ions,

Electrolytes concentration and necessity:

A ratio of Na and K concentration within extra- and
intra- cellular fluids must be maintained as follows:
lons Extra cell fluids Intra fluids
Conc. mmol/L
Na 140 10
Ca 2.5 0.1
CI 100 4
K 140
Mg 1.5 30
PO 2 60
 Functions of electrolytes
clectrolytes Functions
Tntracelular Enzymatic assistance in energy productions to
K, Mg, PO mitochondria

Energy reservation, energy transfer

Extracellular Regulatesenzymatic reactions, Energy transport
Na, Ca, Cl and distribution

Migration of molecules and ions through cell membrane

o Unhydrated molccules-H,0, O,, CH,0, by simple diffusion
o Hydrated molecules or ions-can't migrate by diffusion duec
to the following three reasons:
a. Size of hydrated ions,

b. lipid insolubility,
c. Diclectric constant-higher in extra fluid
 Ways to ion migration:

Passive transport-carrier (ligands) assisted transport

by diffusion through membrane
Active transport through ion channel
i. Ligand facilitated diffusion
ii. Sodium-potassium pump:
a. neurotransmitor controlled, b. Voltage
controlled migration-
working against conc. gradient that requires
energy which is obtained by hydrolysis of ATP
 Cell membrane
Fluid Mosaic Model'to cxplain relationship to clectrolytes
migration
Membrane-thickness 70A°
made up of lipid and protein
consist of lipid bilayer where globular protein float as
icebergs.
It contains ion channcls.
Glycoprote roe h Glycolp lgd wth Extracelular
caibehyoae shahed artoyl

Phospholipid
blayer

Pergher iniae Phogholpe intracelular

prutein blayer Hydaphebic tal
wegral membrane eec Pheten thunnes
pro
Nctsktal amerts Hydrophilic head
Fluid mosaic model
Carrier molecules:
Known as cavitants - macrocyclic molecules:

Properties-
o polar interior for binding metal ions and nonpolar
exterior group enabling metal ions to cross cell
membrane
o alkali ions may be brought into solution in solvents
rather than water
Types: three categories
i. lonophore: Macrocyclic or acyclic compounds
ii. Crown compounds: Cyclic ether
ii. Cryptands: Polycyclic ether
Ionophores: polypeptides eg.metal Valinomycin, nonactin,
monactin, actinomycin,
*
encapsulated in biology
ion
Naturally occurring small eyclice polypetides, *play an important
roles in transporting metal ions encapsulating across the membranes.

Valinomycin

H CHs H CH
L-valine D-hydrory D-valine L-lactic
30Valeric acid acid
Valinomycin is a dodecadepsipeptide antibiotic

R-H, R-Me, Monactin

lonic radii: K*> Nat
o-Phe
o Valinomycin, nonactina and monactin
having bigger cavity able to transport
K than Na*
Leu

logK 0.67 for Na/valinomycin,

4.90 for K/valinomycin
Instead actinomycin having small cavity
o
o
size able to transport Nat than K*
o Universal ionophore- Gramicidin -

encapsulate all of Li", K, Na", Rb

o X-ray evidence: carbonyl groups are
coordinated with M",

Gramicidin
Universal ionophore

Facilitated diffusion in cell membrane-as complex

Cyclic ether: Crown Compounds
Naming: substituents no. of atoms in ring no. of oxygen donors
e.g. dicyclohexyl-14-crown-4; dibenzo-12-crown-4; 18-crown-6;
dibenzo-1 8-crown-6; dicyclohexyl-18-crown-6; dicyclohexyl-21-
crown-7; dicyclohexyl-24-crown-8.
Diphenyl-18-crown-6 is the first synthesized crown compd.
Relation bctween ionic radi and no oxygen donors for the
formation of 1:1 complex as follows
Li+, Na+, K+, Rs+bond with crown having 4, 5, 6, 8 oxygen
donors, respectively.
*Bonding- electrostatic.

Potassium complex of a crown ether

 Formation const: Due to cavity
size and ionic radii relation.
logk-Na log-K
18-crown-6 0.30 2.06

dicyclohexyl 3.50 0.61

al Crown ether
16-crown-5
Bonding constant of 18-crown-6 increases in the order
Li < Na', Cs+ < Rb' <K*
Strongest bond K with 18-crown-6
Strongest bond Rbt with dicyclohexy1-21-crown-7
Strongest bond Cs with dieyclohexy-24-crown-8
Strongest bond Li with dicyclohexyl-14-crown-4
cationic rad0.80-0.97
Size ranoCrowncavity
Ratio greater than 1 is undesirable as crown cavity is
too small to surround metal ion effectivcly.
Other factors that influence the stability of crown-
metal ion complex:

Greater the no. of oxygen atoms in ring greater will

be the ion-dipole interaction.
Binding is enhanced where donor oxygen atoms are
coplanar.
Oxygen atoms should be symmetrically placed
around rimg.
Crown ethers should not be hindered.
For minimum binding-crown ring should not contain
electron withdrawing substituents because it
would decrease the basicity of the oxygen atoms.
Cryptands: Polycyclic ether
Complexes of cryptands with metal ion are cryptates
Two have nitrogen that bridged with three hydrocarbon
ends two
chain containing one or more oxygen atoms.
Naming: Cryptand-111, Cryp-222, Cryp-333 having 1,2,3 oxygen
atom respectively in each chain.
Cryptands from crown ether in two
differ ways
i. Both N- and O- atoms are incorporated,
i. Having greater chelating effect as they are polycycles
metal ions are surrounded effectively.

Cryptand

2.2.2-Cryptand encapsulating.apotassium.cotio Tpurple)

 Ion channels: for active transport of ions
Formation:
Made of protein chain, cach channcl has 4 units, cach unit
consists connected to each ether. Both C-and N-
of six subunits
terminal of protcin chain are inside. Diameter of channcl-5.8 nm.
Each channcl is for spccific mctal ion.
Functions:
ligand facilitated diffusion,
voltage controlled diffusion through Na-K pump.

etyvawasn

UU
sice
 Ligand facilitated diffusion channel:
o Channels are specified for specific ions but they can cooperate
cach other.
o Due to large deficiency of an ion all channels may allow to
enter this ion.
o Each channel has gates if there is deficiency of specific ion-
a signal is transferred by nurotransmeter like

acetalcholene, gates get opened.

o10-10 ions can migrate per secc.
Effect of Acetylcholine

Synoptic a
Bindino a clefta Na
site Acetyteholine Na a
Cell
mümbrane

Recptors K'a Acetylcholine (Ach

prole hn
Cytoplasmin Na Neurotransmitters
postsynaptic cell
Voltage controlled channels:
Inside the cell a permanent voltage of 80 mV, -ve electrochemal
potential must cxist.
When large excess of Nat entered inside the cell by ion channel -

clectrical potential inside the cell is reduced.

I f electrical potential is reduced to 10 mV gates of voltage
controlled channel inside the cell is opened.
lon channel get 3 Na' and allow them to be out.
Contrary 2K ions from outside the membrane are gel into channel
and allow them to go inside the cell.
etrhula

sme
eran

traciule
FHud (icP)
a ev en

etosing
triggered triggene
t treahnld
hrehaid

w g potentiat
Fram threshaid to peak potantial P
ompe t stm otuntiat Voltage gated Na-channel
- s a mV te 3 0 m o mV)
 Active Outside
transport
Na
eside

t
ATP k t ADP +P

Actie tansport
gainst concentraon
godent e h
nut of energy

Inside Outside
K
100 mM 5 mM
Na
10 mM 150 mM
Cell Membrane
o For both action these channels are specifically prepared.
o Both migration happencd against gradicnt so cnergy is
required.
o Energy is produced from hydrolysis of ATP catalyzed by
ATP-ase cnzyme.

ATpATPase

ADP+ Pi
Intra cellular electric is gradually increase to 80 mV
potential
Activity of both ionic channels are repeated and an electric
wave due to the electrochemical disturbance is created and is

transferred as nerve impuse indicating the existing of life.

Did it come about by evolution
Or
was it designed?

T61

3 33T116
Electrolytes such as potassium, sodium, and magnesium help regulate
everything from your kidneys to your heart function.

Functions Sodium:
Sodium is both an electrolyte and mineral. It helps keep the water (the
amount of fluid inside and outside the bodys cells) and electrolyte
balance of the body. Most of the sodium in the body (about 856) is found in
blood and lymph fluid. It helps maintain normal blood pressure, supports the
work of your nerves and muscles, and regulates your body's fluid balance.

A normal blood sodium level is between 135 and 145 milliequivalents per
liter (mEq/L). In many hospital laboratories 155-160 mEa/L is chosen as the
upper critical value, is associated with high risk of death. Americans consume
less than 2,300 milligrams (mg) of sodium per day as part of a healthy eating
pattern. adults eat more sodium than they should-an average of more than
3,400 mg each day.
Functions of potassium:
Potassium ions are
primarily found inside the cell.
Increasing potassium intake can reduce the risk of cardiovascular diseases,
such as heart disease and stroke, by lowering blood pressure. Potassium ions
maintain the osmolarity (the concentration of a solution expressed as the
total number of solute particles per litre) of the cell. They also regulate the
opening and the closing of the stomata.
The more potassium you eat, the more sodium you lose through
urine. Potassium also helps to ease tension in your blood vessel walls,
which helps further lower blood pressure. Increasing potassium through diet
is recommended in adults with blood pressure above 120/80 who are
otherwise healthy.
Consuming high amounts of sodium and low amounts of potassium can
increase a person's risk for heart disease and stroke. Potassium levels often
change with sodium levels. Potassium levels are also affocted by a hormone
called aldosterone, which is made by the adrenal glands.
Hyponatremia occurs when the sodium in your blood falls below 135
mEq/L. When sodium levels in the body are low, water tends to enter cells,
causing them to swell. When this occurs in the brain, it is referred to as
cerebral edema. Cerebral edema is particularly dangerous because the brain
is confined in the skull without room for expansion, and the swelling can
lead to brain damage as the pressure increases within the skull. Cerebral
edema occurs only in severe cases of hyponatremia. Viscosity of blood
increases causing heart problem, blood circulation irregulations.

Hypernatremia Too much sodium can increase your risk for high blood
pressure, stroke, and heart failure. It can also increase your risk
for osteoporosis, stomach cancer, kidney disease, kidney stones, an
enlarged heart muscle and headaches. Too much sodium can also affect
your appearance

Hypernatremia typically causes thirst. The most serious symptoms of

hypernatremia result from brain dysfunction. Severe hypernatremia can
lead to confusion, muscle twitching, seizures, coma, and death.