Chemical elements essential to life forms can be divided into the following

(i) Bulk elements: C, H, N, O, P, S

3-

Macrominerals and ions: Na, K, Mg, Ca, Cl, PO4 , SO4

(iii)

Trace elements: Fe, Zn, Cu

(iv)

Ultratrace elements comprises of

2-

(ii)

(a) non-metals: F, I, Se, Si, As, B

(b) metals: Mn, Mo, Co, Cr, V, Ni, Cd, Sn, Pb, Li

Essentiality of elements is defined by

(1)
A physiological deficiency appears when the
element is removed from the diet

(2) The deficiency is relieved by the addition of that

element to the diet

(3) A specific biological function is associated with the

element

Every essential element follows a dose-response

curve

At lowest dosages organism does not survive

In deficiency regions, the organism exists with less than

optimal functions

After optimal dosage (plateau region), higher dosage cause

toxic effects in the organism eventually leading to lethality

Active Site and Enzyme Substrate Complex

The active site of an enzyme is the region that binds the substrate
and contributes the amino acid residues that directly participates
in the making and breaking of chemical bonds
Generalizations
1) Enzymes are usually very large compared to the substrate
Only a small portion is involved in ES complex
Rest portion is involved in control and maintaining of structure

2) The substrate is bound by relatively weak forces

G E-S complex = (12 to 36) KJ mol

-1

-1

(strength of a covalent bond is upto ~ 450 KJ mol )

3) Active sites are designed to exclude H2O

Surrounded with non-polar amino acids to create a hydrophobic environment

Essential for substrate binding and product formation (Catalysis)

Specificity
Active site provides specificity for its particular substrate

Substrate has a matching shape to fit into the active site

(Lock and Key mechanism)

Formation of Enzyme-Substrate Complex is thus crucial to the

product formation

Evidence for Enzyme-Substrate Complex

(1) At constant [E], increasing the [S] will increase the reaction rate until a
maximum velocity is reached,

(2)

Isolation of E-S complex

(3)

X-ray diffraction studies of E-S complex

(4)

Spectroscopic studies of E-S complex

Active sites of
Enzymes
Cys(S)
Zn

His(N)

OH

Zn

OH2 Cys(S)

Glu(O)

His(N)

His(N)
Carboxy
peptidase

His(N)
Zn OH

His (N)

H O + CO
2

His(N)
Carboxy
anhydrase

CH CH OH

peptide
hydrolysis
(removes
terminal
amino acids
from
proteins)

NAD+
NADH

H2CO3

+ HCO

3-

Liver Alcohol dehydrogenase

H3
C
H
O

Porphyrins
Porphyrins are tetrapyrrole macrocycles with conjugated double
bonds and various groups attached to the perimeter
R

N
R

R
NH

HN
R

Variation of substituents facilitates the tuning of electrondonating and electron-withdrawing ability of the ligand

The porphyrins can accept two hydrogen ions to form+2 diacids or donate
two protons to form -2 dianions

Porphyrins are found in many metalloenzyme

Enzyme

Function

Fe-porphyrin

Cytochrome

electron transfer

Fe-porphyrin

Hemoglobin
Myoglobin

dioxygen carrier

Mg-porphyrin

Chlorophyll

photosynthesis

Cytochromes
Cytochromes are electron transfer proteins
There are three types of cytochromes depending upon the porphyrin types

cytochrome a, cytochrome b, cytochrome c

s-cys protein

s-cys protein

HO

HO

N
Fe

Fe

Fe
N

O
H
HO

OH
O

OH

HO
O

HO

OH
O

Depending upon the ligand, the redox potential of a given cytochrome

can be tailored to meet specific need in electron transfer schemes
(photosynthetic versus respiration)
The potentials are such that the electron flow is from

O2

Cytochrome a is capable of binding O2 and reducing them

Cytochrome a is responsible for severe toxicity of CN
-

th

III

CN binds to the 6 site and stabilize Fe to such an extent that

it cannot participate in electron transfer shuttle

p
ar
a
m
a
g
n
et
ic
4

t 2g
2
eg

w
S
p
i
n
d
t
2

g
6

e
g
0

The size of Fe

2+

increase by 28% on going from

Low spin (oxyhemoglobin) (0.61 )

to
High spin (Deoxyhemoglobin) (0.78 )
2+

The Fe in deoxyhemoglobin is too large to fit in the ring and

o
is situated (0.7-0.8)A above the ring
Thus, presence of O2 changes the electronic arrangement of Fe
and distorts the shape of the complex

2+

The globular protein prevents the irreversible oxidation of Fe(II) to Fe(III)

Cooperativit
y
W
h
e
n
O
2

b
i
n
d
s
t
o
o
n
e
s

u
b
u
n
i
t

trigg
ers
confor
mation
al
change
s in the
globin
chain

t
r
a
n
s
l
a
t
e
d
t
h
r
o
u
g
h

H
b
o
n
d
n
e
t
w
o
r
k

Fe

2+

moves

co
nt
ra
ct
s,
m
ov
es
in
to
pl
an
e
of
po
rp
hy
ri
n
ri
ng

the
histidin
e
attache
d to it

En
ha
nce
s
the
abi
lity
of
oth
er
thr
ee
uni
ts
to

bind

O2

This
phenomenon is
called
cooperative
effect
In a similar way
when the blood
reaches the muscle,
only one O2 is
released, the others
are released even
more easily due to
the cooperative effect
in reverse