metal ions fr cr mg ni zn k na biological reactions

1. Metal Ions
In
Biological Systems
Dr. MishuSingh
Department of Chemistry
Maharana Paratap Govt. P.G College
Hardoi.

2. Progressive modification of Nomenclature
1960s - Inorganic biochemistry
1980s - Bioinorganic Chemistry
2000 - Biological Inorganic Chemistry

3. 1.What is biological inorganic chemistry (biochemistry)?
2. Functional roles of biological inorganic elements
3. Metal ions and proteins: binding, stability and folding
4. Vitamin B12 - Cobalt an essential element for life
5. Bio-mineralization
6. Metals in medicine
7. Poisoning by metals

4. What Is Biological Inorganic Chemistry
(Bioinorganic Chemistry)?
 An interdisciplinary research field at the interface of
the more classical areas of inorganic chemistry and
biology/biochemistry.
 Understanding the roles that metallic and non- metallic
elements play in biological systems is the goal of
biological inorganic (bioinorganic) chemistry.

5. There are two main fields of bioinorganic
chemistry:
1. Investigations of inorganic elements in processes e.g.
nutrition, the toxicity of inorganic species, including
the ways in which such toxicities are overcome both
by natural systems and by human intervention, and of
metal-ion transport and storage in biology.
2. The introduction of metals (metal complexes) into
biological systems as probes and drugs.

6.  The familiar elements C, H, N, O, P and S, the big
six, which are well covered in biochemistry texts
provide the major building blocks for cellular
components including proteins, nucleic acids, lipids-
membranes, polysaccharides and metabolites.
 Despite this organic diversity, life cannot survive
with only these principle elements.

7.  Inorganic elements are also essential to life
processes - eleven elements of the periodic table are
required for all forms of life and an additional seven
or eight elements are used by organisms on our
planet.
 Blood known to contain iron since the 17th century.
 Need for Zinc, 1896.

8. Criteria for ESSENTIALITY of Elements
Should be present in the tissues of different animals at
comparable Concentrations
A specific biochemical function (structural or catalytic or
regulatory type) should be associated with that particular element
Physiological deficiency appears when the element is removed
from a purified diet
The deficiency can be relieved by the addition of that specific
element.

9. Inorganic
Chemistry
Biochemistry
Microbiology
Physiology Physics
Pharmacology Toxicology
Bio-inorganic
chemistry

10. Aspects Concerned In Bioinorganic Chemistry
Which are the elements ESSENTIAL for living cells in biology?
What AMOUNTS are these present?
How are these CHOSEN?
Are there any MUTUAL INTERACTIONS AMONG these
elements of biology?
 HOW and WHERE are these present in biological systems?
 WHAT do these elements DO in biological systems?
 HOW do these elements DO THOSE FUNCTIONS/JOBS?

11. Recent Concerns
HOW important is that particular element in that particular
function?
WHAT HAPPENS when you replace that element of biology by
a different one?
WHEN you replace that particular binding site or amino acid
residue by another?

12. Evolution Of Life Essential Elements
Earth solidified ~ 4 billion years ago
“80 stabile elements”
Chemical elements essential to life forms can be divided into the
following:
(i) Bulk elements: C, H, N, O, P, S
(ii) Macrominerals and ions: Na, K, Mg, Ca, Cl, PO4
3-, SO4
2-
(iii) Trace elements: Fe, Zn, Cu
(iv) Ultratrace elements comprises of
(a) non-metals: F, I, Se, Si, As, B
• (b) metals: Mn, Mo, Co, Cr, V, Ni, Cd, Sn, Pb, Li

13. Periodic Table

14. Functional roles of selected biological inorganic elements
 Charge balance and electrolytic conductivity: Na, K, Cl
 Structure and templating: Ca, Zn, Si, S
 Signaling: Ca, B, N, O
 Bronstead Acid-Base Buffering: P, Si, C
 Lewis Acid-Base Catalysis: Zn, Fe, Ni, Mn
 Electron Transfer: Fe, Cu,
 Group Transfer (e.g. CH3, O, S): V, Fe, Co, Ni, Cu,
Mo, W
 Redox Catalysis: V, Mn, Fe, Co, Ni, Cu, W, S, Se
 Energy Storage: H, P, S, Na, K, Fe
 Biomineralization: Ca, Mg, Fe, Si, Sr, Cu, P

15. Metals essential for life:
The role for most is uncertain
Na, K, Mg, Ca
V, Cr, Mn, Fe Co, Ni, Cu, Zn
Mo, W

16. Metal Ions
• Ca2+
• Mg2+
• Fe2+
• Cu2+
• Zn2+
• Co3+
• Na+
• K+
Role
-1.5-2% of body mass, bones, teeth
-Bones and teeth, intracellular activity
-Hemoglobin, O2 transfer
-Cofactor in enzymes
-Cofactor in enzymes, growth, healing
-In vitamin B12
-Water balance, nerve impulses, fluids inside
and outside cells

19. 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

20. Alkali metals
Terrestrial distribution:
Li Na K Rb Cs Fr
0.060 nm 0.095 nm 0.133 nm ionic radii
Distribution in vivo:
(Li) Na K (Rb)

21. Role of Na+
• Extracellular fluid
• Osmotic balance “sodium pump”
Mg2+
3Na+
ic + 2K+
ec + ATP4- + H2O 3Na+
ec + 2K+
ic + ADP3- + HPO4
2- + H+
• Acid-base balance
• Conformation of proteins ( nucleic acids)
• Electrical impulse of nerve system

22. Role of K+
• Enzyme activator
• Conformation of proteins
RNA (replication)
• Secretion of gastric acid
• Transmembrane potentials!

23. Complexes Of Alkali Metals (Na+, K+)
 Cyclic antibiotics:
Valinomycin
Monactin
Nonactin
 Polyethers
 Synthetic Cryptands

24. Alkaline Earth Metals
Terrestrial distribution:
Be Mg Ca Sr Ba Ra
Distribution in vivo:
Mg Ca

25. 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+
prothrombin thrombin-fibrinogen-fibrin
Alkaline Earth Metals

26. Transition Metals

27. Transition Metals in Biomolecules
Iron.
Most abundant metal in biology, used by all plants and animals
including bacteria. Some roles duplicated by other metals, while
others are unique to Fe. Iron use has survived the evolution of the
O2 atmosphere on earth and the instability of Fe(II) with respect to
oxidation to Fe(III).
Zinc.
Relatively abundant metal. Major concentration in metallothionein
(which also serves as a reservoir for other metals, e.g. Cd, Cu,
Hg). Many well characterized Zn proteins, including redox
proteins, hydrolases and nucleic acid binding proteins.
Copper
Often participatse together with Fe in proteins or has equivalent
redox roles in same biological reactions. Reversible O2 binding,
O2 activation, electron transfer, O2
- dismutation (SOD).

28. Cobalt.
Unique biological role in cobalamin (B12-coenzymes)
isomerization reactions.
Manganese
Critical role in photosynthetic reaction centers, and SOD
enzymes.
Molybdenum
Central role in nitrogenase enzymes catalyzing N2  NH3,
NO3  NH3
Chromium, Vanadium and Nickel
Small quantities, uncertain biological roles. Sugar
metabolism (Cr);
Ni only in plants and bacteria (role in CH4 production) and
SOD enzymes.

29. Transition Elements Relevant to Bioinorganic
Chemistry: The Bio metals

30. 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

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

32. Human Body
75% Hem-iron
 Hemoglobin
 Myoglobin
 Cytochromes
 Oxidases, P-450
25% Non-hem-iron
 Rubredoxins
 Ferredoxins

33. Cu(I), Cu(II)
Plants Electron transfer
Animals O2-carrying
Cu-proteins and enzymes
 Cytochrome oxidase
 Tyrosinase, phenol oxidase
 Ceruloplasmin
 Blue proteins
 Superoxide dismutase
 Hemocyanin

34. Role of Zn2+
Deficiency:
• Disturbances of reproductive system
• Dwarfism
• Skin lesions
• Skeletal abnormalities

35. TOO MUCH OF A GOOD THING
Wilson’s disease: Cu
Accumulation in the eye

36. Why transition elements are useful in biological
activities and system?
1. Are extremely good catalytic active sites in enzymes
2. Stable in variety of genomatrix
3. Have multiple coordination sites
4. Are stable in variety of oxidation states
5. Have ‘weak’ coordination bonds where needed
6. Are capable of stabilizing intermediates.

37. Metal ions and proteins: binding, stability and folding
 Life has evolved with the minerals of the Earths crust
and the ions in the Earths waters.
Therefore it is not surprising that living beings have
evolved the capability to use inorganic elements for key
biological processes and to defend themselves from
poisoning by other elements.
 Some metal ions, when associated with polypeptides,
can help catalyze unique chemical reactions and perform
specific physiological functions. We call such metal ions
“metal cofactors”.

38. Amino acids and proteins alone are not sufficient to
perform all the reactions needed for life. For example,
the Fe3+/Fe2+ and Cu2+/Cu+ redox couples play
critical roles as cofactors for electron transfer reactions
in the catalysis of redox reactions.
 The Fe2+ ion can reversibly bind dioxygen (O2) if a
coordination site is available.
In the periodic table those metal ions essential for life
are highlighted in green. Some of these e.g. Fe, Cu and
Zn are strongly associated with proteins and form the
so-called metalloproteins.

39. For example, ferritin the
metalloprotein that is the main iron
storage protein in the body.
In mammals iron is bound and
transported by the serum protein
transferrin, and it is stored by ferritin
in most life forms.
Ferritin is a spherical molecule with an
outer coat of protein and an inner core of
hydrous ferric oxide [FeO3(H2O)n].
As many as 4500 atoms of Fe can be
stored in a single ferritin molecule.

40. Some metal ions are found deeply buried within proteins. Such
metal ions are often “structural” in function.
Their interaction with the protein helps insure the optimal protein
structure and contributes to the stability and appropriate acid-base
behaviour necessary for the physiological function.
For example, the Zn2+ ions in Zn fingers which are transcription
factors are necessary for the adoption of the proper shape of the
protein, which allows it to interact with DNA. It is not currently
known if the zinc ion plays more than a structural role in this
proteins i.e. if the Zn2+ concentrations are also used in some manner
to regulate gene expression.

41. Transcription factor has a series of three
zinc fingers, each with a characteristic
pattern of cysteine and histidine
residues that constitute the zinc-binding
site.
A "finger protein" typically has a series
of zinc fingers, as depicted in the figure.
The zinc is held in a tetrahedral structure
formed by the conserved Cys and His
residues. The finger itself comprises ~23
amino acids, and the linker between
fingers is usually 7–8 amino acids.

42. Vitamin B12 has a porphryin core:
 Porphyrins are heterocyclic macrocycles
composed of four modified pyrrole subunits
interconnected at their α carbon atoms via
methine bridges.
Porphyrins are aromatic. That is, they obey
Hückel's rule for aromaticity, The macrocycle
has 26 π electrons in total. possessing 4n+2 π
electrons (n=4 for the shortest cyclic path)
delocalized over the macrocycle.
 Thus porphyrin macrocycles are highly conjugated systems. As a
consequence, they typically have very intense absorption bands in the
visible region.

43. One of the best-known porphyrins is heme, the pigment in red
blood cells; heme is a cofactor of the protein hemoglobin.

44. Concentration and physiological effect
Dose-response Curve

45. CONTINUED……..