CHAPTER 7 – COENZYMES General Definitions • cofactor – a non-protein chemical compound or element that is (1) bound to a protein and (2) required for a protein’s biological activity • cofactors can be subdivided into 2 categories: essential ions & coenzymes - essential ions – generally react with a ligand that is attached to a protein in order to induce protein reactivity (Mg2+ is the most common essential ion) « metal-activated enzymes – proteins that require loosely-bound metal cations « metalloenzymes – proteins that require tightly-bound metal cations - coenzymes – loosely- or tightly-bound organic cofactors « prosthetic groups – tightly-bound cofactors; not usually altered during a biochemical reaction; remains bound to the enzyme during the reaction « cosubstrates – loosely-bound cofactors; generally vitamins that are chemically altered during a biochemical reaction; must be regenerated; dissociates from active site » vitamins – chemical compounds that are (1) required for protein activity and (2) cannot be synthesized biologically; coenzyme precursors that we cannot make ourselves (must get them in our diet) - apoenzymes – proteins/enzymes that require cofactors for functionality but are missing their cofactor (cofactor is not bound, so the enzyme is inactive) - haloenzymes – cofactor-bound proteins/enzymes (activated enzymes) Water-Soluble Vitamins (B vitamins) Vitamin = Niacin Niacin (Nicotinic Acid) Nicotinamide Niacin deficiency effect = pellagra! coenzymes = NADH and NADPH (cosubstrates) NAD+ = Nicotinamide Adenine Dinucleotide NADH = Nicotinamide Adenine Dinucleotide Hydride NADP+ = Nicotinamide Adenine Dinucleotide Phosphate NADPH = Nicotinamide Adenine Dinucleotide Phosphate Hydride NAD+ (Nicotinamide Adenine Dinucleotide) NADH (NAD Hydride) [Oxidized Form] [Reduced Form] NADP+ (NAD Phosphate) NADPH (NAD Phosphate Hydride) [Oxidized Form] [Reduced Form] purpose of NADH and NADPH = to transfer 2 electrons at a time (a hydride, H–, and a proton, H+) to and from metabolites [oxidoreductases] Nicotinamide Mononucleotide (NMN) Adenosine Monophosphate (AMP) r r N glycosidic linkage furanose ringVitamin = Thiamine Thiamine TPP (Thiamine Pyrophosphate) Thiamine deficiency effect = beri-beri coenzyme = TPP (Thiamine Pyrophosphate) (prosthetic group) purpose of TPP = to transfer 2 carbon acyl groups (generally participates in decarboxylation reactions) [carboxylases (oxidative decarboxylations) & transferases (transketolases)] Vitamin = Riboflavin Riboflavin FMN FAD Riboflavin deficiency effects = dermatitis & mouth lesions coenzymes = FMN and FAD (prosthetic groups) FAD = Flavin Adenine Dinucleotide FMN = Flavin Mononucleotide purpose of FAD and FMN = to transfer electrons one at a time; will accept electrons two at a time (donate electrons one at a time due to ability to form a semiquinone) oxidation states of flavins: oxidized quinone form (FMN or FAD) – regular isoalloxazine ring semiquinone form (FMNH" or FADH") – radical form reduced hydroquinone form (FMNH2 or FADH2) – both N’s have an H (\ || \) enzymatic pyrophosphate transfer pyrophosphate thiazoline ring pyrimidine ring isoalloxazine ring ribitolVitamin = Pantothenate Pantothenate deficiency effect = hypertension coenzyme = Coenzyme A (cosubstrate) purpose of Coenzyme A = to transfer acyl groups / catalyzes acyl transfer rxns Coenzyme A is composed of 3 major components: (1) a 2-mercaptoethylamine (bears a free –SH group) (2) the vitamin Pantothenate (3) an adenosine diphosphate moiety the free –SH group is the reactive center Vitamin = Pyridoxine (Vitamin B6) Pyridoxine Pyridoxal Pyridoxamine Vitamin B6 deficiency effects = depression, confusion, & convulsions coenzyme = PLP (Pyridoxal Phosphate) (prosthetic group) PLP (Pyridoxal-5’-phosphate) purpose of PLP = allows transamination reactions to move forward; helps catalyze isomerizations, transaminations, and elimination reactions [transferases (transaminases) & isomerases] Vitamin = Biotin Biotin deficiency effect = sebborhea, rash, & muscle pain coenzyme = NONE / Biotin (prosthetic group that functions as a swinging arm) (covalently bound to the ε-amino group of a lysine residue) + + + – – – H H H –purpose of Biotin = catalyzes carboxyl-group transfer reactions and ATP-dependent carboxylation reactions (puts carboxyl groups on things) other notes: Avidin is a biotin binding protein found in eggs Vitamin = Folic Acid / Folate Folic Acid deficiency effects = anemia & neural tube development coenzyme = THF (Tetrahydrofolate) (cosubstrate) purpose of THF = to transfer one-carbon functional groups (including methyl, methylene, and formyl groups) / catalyzes one-carbon functional group reactions (at any oxidation state) Folic Acid has 3 major components: (1) pterin (2-amino-oxoteridine) (2) a p-aminobenzoic acid moiety (3) a glutamate residue Vitamin = Cobalamin Cobalamin deficiency effect = pernicious anemia coenzyme = Cobalamin (cosubstrate) / adenosylcobalamin purpose of Cobalamin = catalyzes enzymatic rearrangement reactions in which a hydrogen atom and an adjacent group switch positions; methyl transfer reactions; detoxification of chlorinated compounds Vitamin = Lipoic Acid (generally described as a B vitamin; its active form is Lipoamide; an eight-carbon carboxylic acid in which 2 hydrogen atoms, on C6 and C8, have been replaced by sulfhydryl groups, which are connected in a disulfide linkage) Lipoic Acid deficiency effect = NONE coenzyme = Lipoamide (prosthetic group) (swinging arm) purpose of Lipamide = acts as a swinging arm in acyl-group transfer reactions / functions as a swinging arm that carries acyl groups between active sites in multienzyme complexes the disulfide linkage is the reactive centerVitamin = Vitamin C / Ascorbic Acid Ascorbic Acid Vitamin C deficiency effect = scurvy coenzyme = Ascorbic Acid (neither! not a prosthetic group or a cosubstrate) (doesn’t accomplish its job in the active site of an enzyme) purpose of Ascorbic Acid = acts as an oxidizing agent in the synthesis of collagen; can also be categorized as an