Sinh học - Chapter 7 (part 1): Cofactors

Chapter 7 (part 1)CofactorsCofactorsCofactors are organic or inorganic molecules that are required for the activity of a certain conjugated enzymesApoenzyme = enzyme (-) cofactorHoloenzyme = enzyme (+) cofactorInorganic cofactors – essential ionsOrganic cofactors – coenzymes Essential Ion CofactorsActivator ions – bind reversibly to enzyme and often participate in substrate binding.Metal ions of metalloenzymes – cations that are tightly bound to enzyme and participate directly in catalysis (Fe, Zn, Cu, Co).Metal activated enzymes – require or are stimulated by addition of metal ions (i.e. Mg2+, is required by many ATP requiring enzymes)Metal ions can function as electrophiles in active siteZinc protease (angiotensin converting enzyme)CoenzymesCosubstrates- - altered in rxn and regenerated to original structure in subsequent rxn - disassociated from active site - shuttle chemical groups among different enzyme rxns.Prosthetic groups- - remains bound to enzyme - must return to original formBoth cosubstrates and prosthetic groups supply reactive groups not present on amino acid side chainsMetabolite coenzymes – synthesized from common metabolitesNucleoside triphosphates – (ATP) can donate phosphates, pyrophosphates, adenosyl grroupsS-adenosylmethionine (SAM) – donates methyl groupsNucleotide sugars (uridine diphosphate glucose = UDP-glucose) - transfer sugars in carbohydrate metabolism CoenzymesVitamin derived coenzymesMust be obtained from dietSynthesized by microorganisms and plantsVitamin deficiencies lead to disease stateMost vitamins must be enzymatically transformed to function as a coenzymeVitaminsVitamin CoenzymeAscorbic acid (C) not a coenzyme Niacin NAD(P)+/NAD(P)HRiboflavin (B2) FMN & FADThiamin (B1) Thiamin-pyrophosphatePyridoxal (B6) Pyridoxal phosphateBiotin BiotinFolate TetrahydrafolateCobalamin (B12) adenosyl-and methylcobalaminVitamin A RetinalVitamin K Vitamin KPantothenate (B3) Coenzyme A Niacin (nicotinic acid)Deficiencies lead to pellagra (dermatitis, diarrhea, dementia)Required in relatively high amounts compared to other vitaminsNot true enzyme because can be synthesized from tryptophan in the liverNicotinamide CoenzymesNAD+ / NADP+Serve as cofactors in oxidation/reduction reactionsAct as co-substrates for dehydrogenasesReduction of NAD+/NADP+ and oxidation of NADH/NADPH occurs 2 e- at a time.Function in hydride ion transferRxns forming NADH/NADPH are catabolicNADH is coupled with ATP production in mitochondriaNADPH is an impt reducing agent in biosynthetic reactionsReduced forms (NADH/NADPH) absorb light at 340 nm, oxidized forms (NAD+/NADP+) do notRiboflavin (B2)Water soluble vitaminSevere deficiencies lead to growth retardation, reproductive problems and neural degenerationMeat, dairy products and dark green vegetables, legumes and grains are good sourcesFMN/FADFAD and FMN can transfer electrons one or two at a timeHydroquinoneformQuinoneformsemiquinone formThiaminThiamin is the first Vitamin discovered (Vital amine = Vitamin)Deficiencies lead to disease called Beriberi (neurological disorders, heart problems, anorexia)Beriberi prevealent in undeveloped countries where polished grains make up the majority of the diet.Associated with alcohol related disorders (Wernickes-Korskofff syndrome – memory loss, unstable walk) Thiamin pyrophosphateServes as a cofactor in decarboxylation rxn of keto acids Also functions as a prosthetic group in transketolases (catalyze the transfer of two carbon units in carbohydrate metabolism)Thiazolium ring is the chemically active part of TPPYlid = a molecule with opposite charges on adjacent atomsPyridoxalPYRIDOXAL-PHOSPHATEImportant in amino acid metabolismBound to enzyme as a Schiff base thru rxn with lysine PLP functions in transamination, decarboxylation, racemization, isomerization, side-chain elimination rxns involving amino acidsPLP in transamination reactionPLP in amino acid decarboxylation reaction