The document discusses several metalloenzymes and the role of metal ions in their structure and catalytic functions. It begins by explaining that metalloenzymes contain a protein portion and a metal ion prosthetic group that is important for their activity. It then discusses specific metalloenzymes in more detail, including carbonic anhydrase which contains zinc and catalyzes the hydration of CO2, carboxypeptidase which contains zinc and catalyzes peptide bond hydrolysis, and liver alcohol dehydrogenase which contains zinc and catalyzes alcohol dehydrogenase. The document also asks why nature favors zinc in many hydrolytic enzymes and discusses several other metalloenzymes and their metal cofactors.

1. Application of bioinorganic
chemistry with respect to
role of metal enzyme and
metal toxicity
BY PRANAV GANESH DALVI

2. METALLOENZYME
 Enzymes are catalyst for biological system
 The biocatalyst has the main frame-work built of protein but in metalloenzyme
activity depends on the presence of desired metal ion
 Thus metalloenzyme has two structural components : the protein portion
described as apoenzyme and a small non-protein prosthetic group which may be
a simple metal ion or a complexed metal ion

3. CARBONIC ANHYDRASE ENZYME
 Structure : Zn+2 (d10)
Tetrahedral geometry
Three valency is filled with nitrogen of histidine amino acid
and 4th valency is satisfied with water

4. CARBONIC ANHYDRASE ENZYME
Functions :
In 1939,it was established that it is the Zn+2 containing metalloenzyme known as carbonic anhydrase (CA)
responsible for catalysing the reversible hydration of CO2 in blood
CO2 is the starting material in photosynthesis and it is the end product of respiration
Thus the hydration of CO2 and dehydration of H2CO3 is important in animals, plants and several bacteria

5. CARBONIC ANHYDRASE ENZYME
 MECHANISM :

6. QUESTIONS
Q. THE METAL ION OF THE ENZYME INVOLVED IN HYDRATION OF CO2 IS
A. Cu2+
B. Fe2+
C. Mg2+
D. Zn2+

7. CARBOXY PEPTIDASE ENZYME
Structure : Zn2+(d10)
tetrahedral geometry
2 valency is filled with nitrogen of histidine amino acid and 1 with
glutamic acid amino acid and the 4th valency was satisfied with
water

8. CARBOXY PEPTIDASE ENZYME
Functions :
It catalyses the hydrolysis of carboxyl terminal peptide bonds (also known as exopeptidase enzyme )
The Zn2+ containing enzymes are released from their inactive precursors or zymogens (i.e . Procarboxypeptidase)
in the pancreas for the digestion of proteins . This pancreatic enzyme is very much specific to hydrolyse the
terminal peptide linkage at carboxyl end. it shows a marked preference towards expected linkages in which the
side chain of the terminal residue contain some aromatic moiety or branched aliphatic chain with L-configuration
denoted by (θ)

9. LIVER ALCOHOL DEHYDROGENASE
ENZYME (LADH)
Structure : Zn2+ (d10)
Tetrahedral geometry
2 valency is filled with sulphur of cystine amino acid , 1 with
nitrogen of histidine amino acid and 4th valency was satisfied
with water

10. LIVER ALCOHOL DEHYDROGENASE
ENZYME (LADH)
 Functions :
LADH catalyses the reversible dehydrogenation of primary and secondary alcohols to
aldehyde and ketones respectively the reactions use NAD+ /NADH system. The overall
reaction is given below involves hydride transfer followed by loss of proton

11. QUESTION
 Why does nature choose Zn+2 metal ion as the active site for so many hydrolytic
enzyme ?
1. Zn metal ion only exist in +2 oxidation state
2. It is redox inactive
3. It only has tetrahedral geometry
4. It is a borderline hard acid
5. Zn+2 is a good lewis acid

12. PEROXIDASE ENZYME
 Structure : Heme containing enzyme (Iron +porphyrin group)
Fe+3
octahedral geometry
high spin complex
the axial valencies are filled
with nitrogen of histidine
and water

13. PEROXIDASE ENXYME
 Functions:
 Peroxidase catalyses the oxidation of any compound in presence of H2O2
(peroxide)

14. CATALASE ENZYME
 Structure :
 It is a tetramer of peroxidase enzyme
 Heme containing enzyme
 Octahedral geometry
 High spin complex

15. CATALASE ENZYME
 Functions:
 DECOMPOSITION OF H2O2

16. CYTOCHROME P450
 Structure:
 Heme containing enzyme
 Octahedral geometry
 Low spin complex
 Axial valencies are filled with sulphur of cystine and water

17. CYTOCHROME P450
 Functions

18. CYTOCHROME C OXIDASE ENZYME
 Structure :
 Cytochrome c oxidase enzyme consists of four redox centres i.e. CuA , CuB , Heme
a and heme a3

19. CYTOCHROME C OXIDASE
 Functions :
 The electrons from cyt c oxidase are transferred to O2 to reduce it to H2O

20. XANTHINE OXIDASE ENZYME
 Structure :
 It consists of 1 Mo , 2 Fe2S2 (Ferrodoxin) and one FAD unit

21. XANTHINE OXIDASE ENZYME
 Function :
 It catalyses the oxidation of xanthine to uric acid

22. ALDEHYDE OXIDASE ENZYME
 Structure :
 It consists of 2 Mo ,4 Fe2S2 ,2 FAD UNIT

23. ALDEHYDE OXIDASE ENZYME
 Functions :
 It catalyses the oxidation of aldehyde to carboxylic acid

24. Zn-Cu SOD(SUPEROXIDE DISMUTASE)

25. Zn-Cu SOD(SUPEROXIDE DISMUTASE)
 Structure
 As the name suggests it has two copper and zinc site
 zinc and copper both has oxidation state +2
 copper +2 is having square planar geometry
 Zinc +2 it is in a tetrahedral geometry
 In fact copper +2 is equatorially coordinated to 4 histidyl imidazole( his- 46,his-118,
his-44 and his – 61) and a water molecule remains weekly bound to one axial position
to give up highly distorted square pyramidal geometry the zinc +2 center is
coordinated to three histidyl Imidazole( histidine 78 ,histidine 69 and bridging histidine
61) and the carboxylate group of aspartyl residue( Asp- 81) to obtain the tetrahedral
geometry

26. Zn-Cu SOD(SUPEROXIDE DISMUTASE)
Functions :

27. Zn-Cu SOD(SUPEROXIDE DISMUTASE)
 Functions :
 In the enzymatic reaction O2
- reaches the bottom of protein channel where Cu+2
resides and O2 reduces Cu+2 to Cu+1 producing O2. as soon as the Cu+1 center
is produced the bridging imidazolate group histidine 61 is dislodged from the
copper center but remains coordinated with zinc +2 and water protonates the
partially dislodged imidazole group ( as imidazole moiety is highly basic). at the
next step another O2
- anion approaches and oxidises Cu+1 to Cu+2 and O2
-is
reduced to HO2
- which is further protonated by water to give H2O2. thus the Cu -
centre is reversibly reduced and oxidised by successive encounter with superoxide
giving rise to O2 and H2O2 as the respective steps

28. Vitamin B12