QUIMICA

BIOINORGANICA
QF JOSE AVILA PARCO
2015

Bioinorganic chemistry as a highly interdisciplinary

research field
biochemistry

(micro-) biology

Inorganic chemistry

Bioinorganic chemistry
physics

physiology

toxicology

pharmacology
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Evolution of life essential elements

Earth solidified ~ 4 billion years ago
81 stabile elements
Elements of the living organism:
1.

Elements in large scale: 11 elements

H, C, N, O, Na, Mg, P, S, Cl, K, Ca

2.

Elements in small scale: 7 elements

Mn, Fe, Co, Cu, Zn, I, Mo

3.

Elements of a few species: 7 elements

B, F, Si, V, Cr, Se, Sn

QF JOSE AVILA PARCO

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Periodic Table
bulk eliments
for some species
trace eliments

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Concentration and physiological

effect

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Metals

Metals essential for life:

The role for most is uncertain
Na, K, Mg, Ca
V, Cr, Mn, Fe Co, Ni, Cu, Zn
Mo, W

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General roles of metal ions in biology

Na, K: Charge carriers

Osmotic and electrochemical gradients
Nerve function

Mg, Ca: Enzyme activators

Structure promoters
Lewis acids
Mg2+: chlorophyll, photosynthesis
Ca2+: insoluble phosphates
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Alkali metals

Terrestrial distribution:
Li Na K

Rb Cs Fr

0.060 nm 0.133 nm

ionic radii

0.095 nm

Distribution in vivo:
(Li)

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Na K

(Rb)
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Role:
Na+
Extracellular fluid
Osmotic balance sodium pump
Acid-base balance
Conformation of proteins: nucleic acids
Electrical impulse of nerve system

Mg2+
3Na+ic + 2K+ec + ATP4- + H2O
3Na+ec + 2K+ic + ADP3- + HPO42- + H+
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K+
Enzyme activator
Conformation of

proteins

RNA (replication)
Secretion of gastric acid
Transmembrane potentials!

Complexes of alkali metals (Na+, K+)

Cyclic antibiotics
Valinomycin
Monactin
Nonactin
QF JOSE AVILA PARCO

polyethers
cryptands

synthetic
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The valinomycin-potassium complex

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The nonactin-potassium complex

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Macrocyclic ligands

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Alkaline Earth Metals

Terrestrial distribution:
Be Mg Ca Sr Ba Ra
Distribution in vivo:
MgCa

Be, Ba TOXIC!
Sr (not particularly toxic)
90Sr accumulates in bones
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Alkaline Earth Metals

Mg2+
Plants

chlorosis

CHLOROPHYLL
nervous system (tetany)
active transport (intracellular)
enzyme activator (e.g. ATP-ase)
Ca2+ antagonist

Ca2+
Inhibits Mg2+-activated enzymes
Extracellular: clotting (10-3M)
Ca2+
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prothrombin

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thrombin-fibrinogen-fibrin

Chlorofill

The mechanism of the phosphate hydrolysis

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Transition Metals

Fe, Cu, Mo:

Electron-transfer

Redox proteins and enzymes

Oxygen carrying proteins
Nitrogen fixation

Zn:

Metalloenzymes

Structure promoters
Lewis acid
Not a redox catalyst!

Other metal ions: less well defined and more

obscure roles

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Fe(II), Fe(III):
Essential for ALL organisms
In plants: iron deficiency
In human body: 4-5 g
Uptake: ~ 1 mg/day

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In human body

75% Hem-iron
Hemoglobin
Myoglobin
Cytochromes
Oxidases, P-450

QF JOSE AVILA PARCO

25% Non-hem-iron
Rubredoxins
Ferredoxins

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Cu(I), Cu(II)
Plants
Animals

Electron transfer
O2-carrying

Protection of DNA
from O2-

Cu-proteins and enzymes

Cytochrome oxidase

O2

Tyrosinase, phenol oxidase

ox. of phenols

Ceruloplasmin

Fe(II)

Blue proteins

Electron transfer

Superoxide dismutase

Elimination of O2-

Hemocyanin

O2 transport

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H2O
Fe(III)

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Superoxide Dismutase

SOD-Cu2+ + O2.- SOD-Cu1+ + O2

SOD-Cu1+ + O2.- + 2H+ SOD-Cu2+ + H2O2

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Role of Zn2+ :

deficiency:
disturbances of repr. system
dwarfism
skin lesions
skeletal abnormalities

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(Cys X Cys)7
x=nonaromatic amino acid

Zn metalloenzymes: 80!
Zn activated enzymes: 20!

S
(H2O)(1-2)

(H2O)(1-2)

Zn

Zn
N

C
O
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S(N)

Zn
N

S(N)

S
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Function of Zn in metalloenzymes
1.

Structure-promoter

2.

Substrate binder

3.

Lewis acid

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Outlined structure of
apoferritin

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Iron(II)-protoporfirin IXcomplex (HEM)

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Myoglobin
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Hemoglobin
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Catalytic cycle of P-450 enzymes

H2O

RH

ROH

H2O

+A

H2O

e+ AO

H+

e-

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3O
2

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Zink(II) in the active

centre of
carboxipeptidase-A

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The active centre of the

alcohol dehydrogenase
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Coordination environment of the copper

centre in azurin

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Reversible
oxygenation of
hemocyanin

Structure of dimetal centre in Cu-Zn superoxide dismutase

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Supposed structure of Fe-S-Mo cofactor of nitrogenase

12 ATP
N2

12 ATP

3 NADH + 3H+

3 NAD+

3 Ferredoxin
(oxidized)

3 Ferredoxin
(reduced)

Fe protein
(reduced)

Fe protein
(reduced)

Fe-Mo protein
(oxidized)

12 ATP
Fe protein
(oxidized)

N2

Fe-Mo protein
(oxidized)

Fe protein
(oxidized)

Fe-Mo protein
(reduced)

12 ADP + 12 Pi

2 NH3
6 H+

The supposed reaction mechanism of dinitrogenase

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Coordination environment of the Cr3+

centre in the glucose tolerance factor

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