Cofactors, coenzymes and prosthetic group

1. Enzymology
Cofactors & Coenzymes
Namrata Chhabra
M.D. Biochemistry
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2. Cofactors
Cofactors are non-protein
molecules that assist enzymes
during the catalysis of reactions.
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3. Cofactors
• Such an enzyme without
its cofactor is referred to
as an apoenzyme;
• the complete, catalytically
active enzyme is called
a holoenzyme.
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4. Cofactors
• Cofactors can be subdivided into two groups: metals and small
organic molecules
• Cofactors that are small organic molecules are called coenzymes.
• Most common cofactor are also metal ions
• If tightly bound, the cofactors are called prosthetic groups
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5. Cofactors
• Loosely bound cofactors serve functions like those of prosthetic
groups but bind in a transient, dissociable manner either to the
enzyme or to a substrate.
• They are more like co substrates because they bind to and are
released from the enzyme just as substrates and products are.
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6. Prosthetic group
• Tightly integrated into the enzyme structure by covalent or non-
covalent forces.
a) Organic
◦ Pyridoxal phosphate
◦ Flavin mononucleotide( FMN)
◦ Flavin adenine dinucleotide(FAD)
◦ Thiamin pyrophosphate (TPP)
◦ Biotin
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7. Prosthetic group
b) Inorganic
Metals are the most common
prosthetic groups
Metal ions – Co, Cu, Mg, Mn, Zn,
Fe
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8. Role of metal ions
• Enzymes that contain
tightly bound metal
ions are termed –
Metalloenzymes.
• Enzymes that require
metal ions as loosely
bound cofactors are
termed as metal-
activated enzymes
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9. Role of metal ions
Metal ions facilitate
◦ Binding and orientation of the substrate
◦ Formation of covalent bonds with reaction intermediates
◦ Interact with substrate to render them more electrophilic or
nucleophilic
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10. Examples of Metalloenzymes
Metal Enzyme
Zn++ Carbonic anhydrase
Zn++ Alcohol dehydrogenase
Zn++ Carboxypeptidase
Fe+++ or Fe++ Cytochromes
Cu++ or Cu+ Cytochrome oxidase
K+ Propionyl CoA carboxylase
Mg++ Hexokinase
Mn++ Superoxide dismutase
Se Glutathione peroxidase
Mo Xanthine oxidase
Ni++ Urease
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11. Metal activated /Ion activated enzymes
• In a few enzyme-controlled reactions, it is the presence of certain
ions that can increase the reaction rate.
• Ions may combine with the enzyme or the substrate.
• The ion binding makes the formation of an enzyme-substrate complex
happen more easily, because it can affect the charge distribution or
the end shape of the complex.
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12. Metal-activated enzyme
• Amylase catalyzes the breakdown of maltose molecules.
• This enzyme will function properly only if chloride ions are present.
• Without the chloride ions, amylase cannot catalyze the reaction
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13. • Coenzymes serve as recyclable shuttles—or group transfer agents—
that transport many substrates from their point of generation to their
point of utilization.
• The water-soluble B vitamins supply important components of
numerous coenzymes
Coenzymes
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14. Coenzymes
• Chemical moieties transported by coenzymes include:
• Hydrogen atoms or hydride ions,
• Methyl groups (folates),
• Acyl groups (coenzyme A), and
• Oligosaccharides (dolichol).
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15. Classification of Coenzymes
Class-1 Coenzymes- Transport of hydrogen and electrons
Coenzyme Abbreviation Group transferred Enzyme
Nicotine adenine
dinucleotide
NAD
+
- Derived from
niacin
Electron (hydrogen
atom)
Lactate
dehydrogenase
Nicotine adenine
dinucleotide phosphate
NADP
+
- niacin
derivative
Electron (hydrogen
atom)
Glutamate
dehydrogenase
Flavin adenine
dinucleotide
FAD - riboflavin (vit.
B2) derivative
electron (hydrogen
atom)
Monoamine
oxidase
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16. Class-2 Coenzymes
Transport of groups other than hydrogen and electrons
Coenzyme Abbreviation Group transferred Enzyme
Coenzyme A CoA Acyl groups Acetyl CoA carboxylase
Thiamine
pyrophosphate
Thiamine (vit.
B1)
Aldehydes Pyruvate dehydrogenase
Complex
Pyridoxal
phosphate
Pyridoxine (vit
B6)
amino and many other Transaminases,
Decarboxylases, Glycogen
phosphorylase
Biotin Biotin Carboxyl Pyruvate carboxylase
5'-
Deoxyadenosyl
cobalamine
vit. B12 alkyl groups Methylmalonyl mutase
Tetrahydrofolate Folic acid One carbon compounds Thymidylate synthase
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17. Coenzymes
• The water-soluble B vitamins supply important components of
numerous coenzymes.
• Nicotinamide is a component of the redox coenzymes NAD and NADP
• Riboflavin is a component of the redox coenzymes FMN and FAD.
• Pantothenic acid is a component of the acyl group carrier coenzyme
A.
• Thiamin participates in decarboxylation of α-keto acids and folic acid
and
• Cobamide coenzymes function in one-carbon metabolism.
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18. Thank you
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