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Cofactors, coenzymes and prosthetic group

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Namrata Chhabra
Namrata Chhabra

Cofactors and coenzymes are non-protein molecules that assist enzymes during catalysis. Cofactors can be metals or small organic molecules called coenzymes. Enzymes require cofactors to function; without cofactors they are inactive apoenzymes, while with cofactors they are active holoenzymes. Cofactors can be tightly bound prosthetic groups or loosely bound cofactors. Common metal cofactors include ions like iron and zinc, and organic cofactors include coenzymes like NADH and FAD that help transfer electrons and protons in reactions. The B vitamins supply important coenzyme components that transport groups like hydrogen, methyl, and acyl groups to help enzymes cataly

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Enzymology Cofactors & Coenzymes Namrata Chhabra M.D. Biochemistry 15-May-20 NAMRATA CHHABRA 1
Cofactors Cofactors are non-protein molecules that assist enzymes during the catalysis of reactions. 15-May-20 NAMRATA CHHABRA 2
Cofactors • Such an enzyme without its cofactor is referred to as an apoenzyme; • the complete, catalytically active enzyme is called a holoenzyme. 15-May-20 NAMRATA CHHABRA 3
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 15-May-20 NAMRATA CHHABRA 4
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. 15-May-20 NAMRATA CHHABRA 5
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 15-May-20 NAMRATA CHHABRA 6
Prosthetic group b) Inorganic Metals are the most common prosthetic groups Metal ions – Co, Cu, Mg, Mn, Zn, Fe 15-May-20 NAMRATA CHHABRA 7
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 15-May-20 NAMRATA CHHABRA 8
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 15-May-20 NAMRATA CHHABRA 9
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 15-May-20 NAMRATA CHHABRA 10
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. 15-May-20 NAMRATA CHHABRA 11
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 15-May-20 NAMRATA CHHABRA 12
• 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 15-May-20 NAMRATA CHHABRA 13
Coenzymes • Chemical moieties transported by coenzymes include: • Hydrogen atoms or hydride ions, • Methyl groups (folates), • Acyl groups (coenzyme A), and • Oligosaccharides (dolichol). 15-May-20 NAMRATA CHHABRA 14
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 15-May-20 NAMRATA CHHABRA 15
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 15-May-20 NAMRATA CHHABRA 16
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. 15-May-20 NAMRATA CHHABRA 17
Thank you 15-May-20 NAMRATA CHHABRA 18

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Cofactors, coenzymes and prosthetic group

  • 1. Enzymology Cofactors & Coenzymes Namrata Chhabra M.D. Biochemistry 15-May-20 NAMRATA CHHABRA 1
  • 2. Cofactors Cofactors are non-protein molecules that assist enzymes during the catalysis of reactions. 15-May-20 NAMRATA CHHABRA 2
  • 3. Cofactors • Such an enzyme without its cofactor is referred to as an apoenzyme; • the complete, catalytically active enzyme is called a holoenzyme. 15-May-20 NAMRATA CHHABRA 3
  • 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 15-May-20 NAMRATA CHHABRA 4
  • 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. 15-May-20 NAMRATA CHHABRA 5
  • 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 15-May-20 NAMRATA CHHABRA 6
  • 7. Prosthetic group b) Inorganic Metals are the most common prosthetic groups Metal ions – Co, Cu, Mg, Mn, Zn, Fe 15-May-20 NAMRATA CHHABRA 7
  • 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 15-May-20 NAMRATA CHHABRA 8
  • 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 15-May-20 NAMRATA CHHABRA 9
  • 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 15-May-20 NAMRATA CHHABRA 10
  • 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. 15-May-20 NAMRATA CHHABRA 11
  • 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 15-May-20 NAMRATA CHHABRA 12
  • 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 15-May-20 NAMRATA CHHABRA 13
  • 14. Coenzymes • Chemical moieties transported by coenzymes include: • Hydrogen atoms or hydride ions, • Methyl groups (folates), • Acyl groups (coenzyme A), and • Oligosaccharides (dolichol). 15-May-20 NAMRATA CHHABRA 14
  • 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 15-May-20 NAMRATA CHHABRA 15
  • 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 15-May-20 NAMRATA CHHABRA 16
  • 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. 15-May-20 NAMRATA CHHABRA 17