Cofactors and Coenzymes

Saint Petersburg University Institute of Chemistry Biomedicinal Chemistry Laboratory Cofactors and Coenzymes Lecture Cofactors • Groups or molecules (other than amino acid residues) which are important to catalysis • Metals • Coenzymes • If tightly bound, it is called a prosthetic group • Enzyme without prosthetic group (cofactor) • Apoenzyme • Enzyme with prosthetic group (cofactor) • Holoenzyme Catalysis by Coenzymes Some common coenzymes Transfers • Oxidation/Reduction • Nicotinamide Adenine Dinucleotide (NAD+) • Flavin Adenine Dinucleotide (FAD) Hydride ion (H-) Electrons Catalysis by Coenzymes Some common coenzymes • One carbon metabolism – Biotin – Tetrahydrofolate Transfers CO2 One carbon groups O C H to CH3 Catalysis by Coenzymes Some common Transfers coenzymes • Acyl groups and others Acyl groups – Coenzyme A Acyl groups – Lipoic acid – Thiamine pyrophosphate Aldehydes Amino groups – Pyridoxal phosphate and amines – 5’-DeoxyadenosylAlkyl groups cobalamin Vitamin Derived Coenzymes Derived Deficiency Coenzyme from causes NAD Niacin Pellagra FAD Riboflavin Dermatitis (B2) Biocytin Biotin Seborrhea (skin) Tetrahydro- Folate Varies folate Vitamin Derived Coenzymes Coenzyme A Pantothenate Fatigue + others Irritability Thiamine Thiamin (B Beriberi pyrophosphate Pyrodoxal phosphate Pyridoxine (B6) 5’ -Deoxyaden- Vitamin B12 osylcobalamin Varies Pernicious Anemia Examples of Coenzyme Catalysis Uncatalyzed reaction H R C NH3 O C H R O CO2 C NH3 H H R C NH3 H Examples of Coenzyme Catalysis Catalysis with pyridoxal phosphate (Vitamin B6 H H O derivative) O R C C NH3 R O NH H2O + X CH O X X X X C HC O X C N H X N H X Schiff Base Examples of Coenzyme Catalysis H R C NH O H C R O X R X CO2 X X N H C NH HC HC X N H C NH HC X H X X X X X N H X Examples of Coenzyme Catalysis H R C R NH X H H2O CH X X N H R C NH CH X H H X X X N H X C H O NH2 H CH X X X N H X Examples of Coenzyme Catalysis Nicotinamide adenine dinucleotide and alcohol dehydrogenase O C O H 2C - N NH2 OH OH O O O NH2 P O P O O O NAD+ H N N N H R NADH OH OH O C N N CH2 O [H ] H NH2 Examples of Coenzyme Catalysis R H Zn2+ H O N C H O C CH3 H2N H H NAD H C CH3 OH