cobalt enzymes

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COBALT ENZYMES AND THEIR IMPORTANCE IN THE BIOLOGICAL systems

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Page 1: Cobalt Enzymes

COBALT ENZYMES AND THEIR

IMPORTANCE IN THE BIOLOGICAL

systems

Page 2: Cobalt Enzymes

INTRODUCTION TO THE METAL COBALT Cobalt is one of the first transition metal series.

Stable form of cobalt is created in supernovas by the r-process.

It comprises 0.0029% of the Earth's crust

Cobalt occurs in copper and nickel minerals and in combination with sulfur and arsenic in the sulfidic cobaltite (CoAsS), safflorite (CoAs2) and skutterudite (CoAs3) minerals.

Cobalt is not found as a native metal.

Its main ores are cobaltite , erythrite , glaucodot and skutterudite.

Page 3: Cobalt Enzymes

COBALT AS AN ENZYME….??☻ Some metals directly exist as enzymes and in some cases these set of enzymes require a coenzyme or a co-factor for their activity- coenzyme dependent.

☻The enzyme becomes functional only when the coenzyme binds to them.

☻The cobalt is present as a linkage in the corrin ring in these coenzyme and acts as an enzyme, hence called as cobalt enzyme.

☻Example : B12(with corrin ring)

☻There are several enzymes containing cobalt in a form other than that in the corrin ring of vitamin B12.

Page 4: Cobalt Enzymes

COBALAMINE- VITAMIN B12

(COENZYME-COBALT COMPLEX) Water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood.

It contains the biochemically rare element cobalt.

The cobalamin -based proteins use corrin to hold the cobalt.

B12 exists with two types of alkyl ligand : methyl and adenosyl.

MeB12 promotes methyl (-CH3) group transfers.

The adenosyl version of B12 catalyzes rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents , an oxygen atom of an alcohol, or an amine.

Page 5: Cobalt Enzymes

Vitamin B12 and its coenzyme forms are prominent cobalt-containing cofactors.

They are part of the larger class of the natural tetrapyrrolic metal complexes.

It has a group of cobalt-containing vitamer compounds which include :--- cyanocobalamin (an artifact formed from using activated charcoal, which always contains trace cyanide , to purify hydroxycobalamin)

--- hydroxocobalamin (another medicinal form, produced by bacteria)

--- the two naturally occurring cofactor forms of B12 : adenosylcobalamin and methyl cobalamin.

B12 is the most chemically complex of all the vitamins.

The structure of B12 is based on a corrin ring.

Page 6: Cobalt Enzymes

STRUCTURE

---It is a COENZYME-COBALT COMPLEX where the metal ion is situated at the centre of the macrocyclic planar ring compound of 4(four) pyrrole derivatives.

---Cobalt metal ion is directly bonded to the 5’ carbon atom of the deoxyribose moiety . ---- This furher bonded to adenine.

---On the other side of the ring , cobalt is attached to the dimethyl benzimidazole base .

----- This in turn is linked to the side chain of a pyrrole ring through ribose and phosphate moieties.

Page 7: Cobalt Enzymes

Formula: C63H88CoN14O14P

Mol. Mass :1355.37 g/mol

Co linked to 5’deoxyadenosyl

Again Co attached to dimethylbenzimidazole base.

In turn linked to side chain of pyrrole ring through ribose and phosphate moieties.

COBALAMINE

Page 8: Cobalt Enzymes

There are various forms of the cobalamin (so called due to the presence of cobalt) molecule.

Some of these are; methyl-, cyano, adenosyl- and hydroxocobalamin (B12b).

There are also nitrite (B12c), sulphito and aquacobalamins.

Most of the B12 present in animal tissues is in one of the two coenzyme forms, adnosylcobalamin or methylcobalamin, and not actual vitamin B12 (cobalamin), which may be present due to diffusion from gut bacteria or active transport using intrinsic factor.

Cobalamin coenzymes are part of the prosthetic group, that is the tightly bound group of coenzymes.

Page 9: Cobalt Enzymes

MAIN SOURCES - COBALT ENZYMES.

Page 10: Cobalt Enzymes

NON- CORRINOID FORMS.

Cobalt also exists as enzyme in non-corrinoid forms..!!

Non- corrin cobalt is receiving increased interest not only in bioinorganic chemistry but also in biotechnology.

Its availability and remarkable chemical versatility makes cobalt an invaluable catalyst in the chemical industry.

Eight noncorrin - cobalt-containing enzymes have been isolated.

Methionine amino peptidase, Prolidase, Nitrile hydratase, glucose isomerase, Methylmalonyl-CoA carboxytransferase, Aldehyde decarbonylase, lysine-2,3-aminomutase, and bromoperoxidase.

Page 11: Cobalt Enzymes

Enzyme or protein

Source Cofactor content

Postulated role for cobalt

Methionine amino peptidase

Animals, yeast, bacteria

2 Co per subunit Hydrolysis

Prolidase Archae 1–2 Co per subunit Hydrolysis

Nitrile hydratase Actinomycetes and bacteria

1 Co in each α-subunit

H2O activation, CN-

triple-bond hydration and protein folding

Glucose isomerase Actinomycetes 1 Co per 4 subunits Isomerization

Cobalt transporter Actinomycetes and yeast

Cobalt uptake

Methylmalonyl-CoA carboxytransferase

Bacteria 1 Co, 1 Zn per subunit

Carboxytransferation

Aldehyde decarbonylase

Algae 1 Co- porphyrin per αβ subunit

Decarbonylation for Aldehyde

Lysine-2,3- aminomutase

Bacteria 0.5–1 Co per subunit

Mutation

Bromoperoxidase Bacteria

≈0.35 Co per 2 subunits

Bromination

Cobalt-porphyrin-containing protein Bacteria

1 Co-porphyrin per protein

Electron carrier

Known cobalt-containing enzymes (non- corrinoid )

Page 12: Cobalt Enzymes

cobalamin plays a number of crucial roles in many biological functions.

♦Biochemical process must happen wherever and whenever they are required.

♦Enzymes can occur in biological fluids as soluble materials or as bound entities to the membrane or could be even part of a huge enzyme complex.

♦These are the proteins whose back bone is made up of a chain of peptide linked amino acids with a variety of structures.

♦Cobalt is less frequently encountered in metalloenzymes but nevertheless an important cofactor in vitamin-B12-dependent enzymes.

Page 13: Cobalt Enzymes

♦It is used as a concentrated source of γ radiation in cancer therapy and food sterilization, and as a radioactive tracer in biological and industrial applications.

♦It has also served as a spectroscopic probe in metalloenzymes.

♦Substituting cobalt for zinc has often been a useful tool to investigate the structural basis of catalytic properties in zinc enzymes.

♦B12 is normally involved in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production.

Page 14: Cobalt Enzymes

Coenzyme B12's reactive C-Co bond participates in three main types of enzyme-catalyzed reactions. They are as follows :

Isomerases: Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine.

Methyltransferases: Methyl (-CH3) group transfers between two molecules.

Dehalogenases: Reactions in which a halogen atom is removed from an organic molecule. Enzymes in this class have not been identified in humans.

Page 15: Cobalt Enzymes

Conclusion:

Although metal ions play a variety of roles in natural proteins, including nucleophilic catalysis, electron transfer, and the stabilization of protein structure, the functions of cobalt have rarely been studied.

Cobalt is used in a limited number of enzymes, unlike iron and zinc.

Page 16: Cobalt Enzymes

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