Bioinorganic chemistry is a highly interdisciplinary field that studies the roles of metals and metalloids in biological systems. Key points:
- 11 elements make up the majority of living organisms by mass, including H, C, N, O, Na, Mg, P, S, Cl, K, and Ca. Metals like Fe, Cu, Zn, Mo, and Mn also play important roles.
- Metals are essential for life, serving as enzyme activators, charge carriers that maintain osmotic gradients, and components of oxygen-carrying and electron transfer proteins. However, both deficiency and excess of metals can cause disease.
- Transition metals Fe, Cu, and Mo are important for electron
2. Bioinorganic chemistry as a highly interdisciplinary
research field
Inorganic chemistry
biochemistry
(micro-) biology
physiology physics
pharmacology toxicology
Bioinorganic chemistry
3. 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
7. Metals essential for life:
The role for most is uncertain
Na, K, Mg, Ca
V, Cr, Mn, Fe Co, Ni, Cu, Zn
Mo, W
8. 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
15. Alkaline Earth Metals
Terrestrial distribution:
Be Mg Ca Sr Ba Ra
Distribution in vivo:
Mg Ca
Be, Ba TOXIC!
Sr (not particularly toxic)
90Sr accumulates in bones
19. Other metal ions: less well defined and more
obscure roles
Zn: Metalloenzymes
Structure promoters
Lewis acid
Not a redox catalyst!
Fe, Cu, Mo: Electron-transfer
Redox proteins and enzymes
Oxygen carrying proteins
Nitrogen fixation
20. Fe(II), Fe(III):
Essential for ALL organisms
In plants: iron deficiency
In human body: 4-5 g
Uptake: ~ 1 mg/day
21. In human body
75% Hem-iron
Hemoglobin
Myoglobin
Cytochromes
Oxidases, P-450
25% Non-hem-iron
Rubredoxins
Ferredoxins
22. Cu(I), Cu(II)
Plants Electron transfer
Animals O2-carrying
Protection of DNA
from O2
-
Cu-proteins and enzymes
Cytochrome oxidase O2 H2O
Tyrosinase, phenol oxidase ox. of phenols
Ceruloplasmin Fe(II) Fe(III)
Blue proteins Electron transfer
Superoxide dismutase Elimination of O2
-
Hemocyanin O2 transport
24. Role of Zn2+ :
deficiency:
disturbances of repr. system
dwarfism
skin lesions
skeletal abnormalities
25. Zn – metalloenzymes: 80!
Zn activated enzymes: 20!
(Cys – X – Cys)7
x=nonaromatic amino acid
Zn Zn Zn
(H2O)(1-2) (H2O)(1-2)
S
S
S
S
S(N)
S(N)
N
N
N
O
O
C
26. Function of Zn in metalloenzymes
1. Structure-promoter
2. Substrate binder
3. Lewis acid
30. Catalytic cycle of P-450 enzymes
S
Fe
H2O
III
S
Fe
III
RH
RH
Fe
S
II
S
Fe
O
O
RH
III
S
Fe
O
O
RH
III
S
Fe
O
R H
IV
RH
H2O
e-
3O2
e-
H2O
2 H+
H2O
ROH
+ AO
+ A
34. Fe S
S Fe
S
Fe
S Fe
S Fe
Fe S
Fe
S
Fe S
S
S
S
Mo
S
Supposed structure of Fe-S-Mo cofactor of nitrogenase
3 NADH + 3H+
3 NAD+
3 Ferredoxin
(oxidized)
3 Ferredoxin
(reduced)
Fe protein
(reduced)
Fe protein
(oxidized)
Fe protein
(oxidized)
Fe protein
(reduced)
12 ATP
12 ATP
12 ADP + 12 Pi
Fe-Mo protein
(oxidized)
Fe-Mo protein
(reduced)
Fe-Mo protein
(oxidized)
N2
2 NH3
6 H+
12 ATP
N2
The supposed reaction mechanism of dinitrogenase