General Definitions CHAPTER 7 COENZYMES 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 r r N glycosidic linkage furanose ring NAD Nicotinamide Adenine Dinucleotide NADH NAD Hydride Oxidized Form Reduced Form e id t o e cl u n o n o M e d i m a n ti o c i N e t a h p s o h p o n o M e in s o n e d A N M N P M A NADP NAD Phosphate Oxidized Form NADPH NAD Phosphate Hydride 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 Vitamin Thiamine pyrimidine ring enzymatic pyrophosphate transfer thiazoline ring Thiamine TPP Thiamine Pyrophosphate Thiamine deficiency effect beri beri coenzyme TPP Thiamine Pyrophosphate prosthetic group p yro p h o s p h ate purpose of TPP to transfer 2 carbon acyl groups generally participates in decarboxylation reactions carboxylases oxidative decarboxylations transferases transketolases Vitamin Riboflavin g n ri e n i z a x lo l a o s i ol t bi ri 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 Vitamin 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 H H Pyridoxal Pyridoxine Pyridoxamine Vitamin B6 deficiency effects depression confusion convulsions coenzyme PLP Pyridoxal Phosphate prosthetic group H 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 amino group of a lysine residue 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 center Vitamin 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 antioxidant acts as a reducing agent during the hydroxylation of collagen Lipid Soluble Vitamins Vitamin Vitamin A Retinal Vitamin A deficiency effect night blindness coenzyme Retinal prosthetic group in the enzyme rhodopsin Retinol or Retinoic Acid purpose of Vitamin A aids in photoisomerizations of proteins in the retina other notes retinol can be obtained directly from food comes from carotenoids in colored veggies or can be synthesized from carotenes Vitamin Vitamin D Cholecalciferol Vitamin D deficiency effect rickets bone development failure coenzyme NONE purpose of Vitamin D regulates Ca2 uptake in the bones other notes converts non enzymatically to 7 dehydrocholesterol through photoisomerization Vitamin Vitamin