生物化学教学课件：Vitamin and Coenzyme

1、Vitamin and CoenzymeVita : life Amine : containing N(1st vitamins contained nitrogen)Vitamins are organic, essential nutrients reqd in minute amounts to perform specific functions that promote growth, reproduction, or the maintenance of health & lifeVitaminsHow vitamins differ from the energy-yieldi

2、ng nutrientsStructureVitamins are individual units, not long chainsFunctionDo not yield energy but assist in releasing energy from carbohydrates, fats and proteinsFood contentSmall amounts needed daily (micrograms and milligrams)Other CharacteristicsOrganic NatureCan be destroyed so food needs to be

3、 handled with care to avoid loss in storage or cookingSolubilityHydrophilic: water solubleB vitamins and vitamin C, lipoic acid Hydrophobic: fat solubleVitaminA, D, E and KWater-SolubleAbsorbed directly into bloodTransported freely Circulate in body fluidsKidneys remove excessUnlikely to reach toxic

4、 levelsFrequent, small doses reqd (1-3 days)Fat - SolubleAbsorbed into lymph, then into bloodMany need protein carriers for transportStored in cells with fatNot easily excretedReaches toxic levels when consumed in excessPeriodic doses reqdWater and Fat-Soluble VitaminsVitamin functions: Coenzymes in

5、 catalyzed reactions (derivates of vitamin Bs)Some vitamins are considered as hormones (vitamin A & D)Antioxidants (vitamins C & E) Some enzymes may require the help of some other small molecule or ion to catalyze a reaction, coenzymes are not irreversibly changed during catalysis; Each kind of coen

6、zyme has a particular chemical function. The number of important coenzymes is limited, but each of them is associated with many different enzymes.CoenzymesUDP-galactose converting to UDP-glucose -OH at position 4 changes its stereochemical orientation-OH changes to a carbonyl羰基 as an intermediate st

7、ate.NAD+ and NADH as coenzyme: never leave the enzyme, reduced and reoxidized in a cyclic fashion, providing a temporary resting place for electrons and the hydrogen from the substrate.Avitaminosis 维生素缺乏症Being lacking of vitamin, obstacle of metabolismDifferent vitamin, different physiology function

8、, different symptom Water-soluble vitaminsthiamin (B1 ) 硫胺素riboflavin (B2 ) 核黄素niacin, niacinamide (PP, B3) 烟酰(胺)pantothenic acid (B5) 泛酸、遍多酸pyridoxine, pyridoxal (B6)吡哆醛biotin (B7)Cyanocobalamin/hydroxycobalamin (B12)folic acid/folate (B9, Vitamin M )lipoic acid/lipoate硫辛酸ascorbic acid (C )B-comple

9、xvitamins1. VitB1 & Thiamine Pyrophosphate (TPP) 焦磷酸硫胺素, 辅羧酶含硫的噻唑环thiazole含氨基的嘧啶环pyrimidinetwo heterocyclic ringsMechanism of action TPP： thiazole is the reactive moiety, carbanion 负碳离子. carbanion can attack the carbonyl carbon of -keto acids, such as pyruvate丙酮酸, giving an addition compoundThiamine

10、 (Vitamin B1) +ATP pyrophosphate group TPP +AMPTPP is used as a coenzyme for all decarboxylations of -keto acids1. Carbanion attack on the carbonylcarbon of a-keto acids to yield an addition compound 加成化合物2. Decarboxylation of the addition compound with the thiazole ring acting as an electron sink i

11、n forming a resonance-stabilized enamine烯胺.3. Protonation of the enamine to form an active acetaldehyde called hydroxyethyl羟乙基-TPP.4. The decarboxylated compound is released, yielding free TPP.5. Carbanion formationenamine烯胺酮戊二酸转酮酶乙酰乳酸合成酶Deficiency seen in those generally malnourished营养不良 and in alc

12、oholicsBeriberi脚气病 - characterized by:loss of sensation in hands and feetmuscular weaknessadvancing paralysisabnormal heart actionThiamin DeficiencyMeats, e.g., liver, pork and hamWhole grain breads and cereals Green leafy vegetablesProlonged cooking can destroy thiaminFood Sources2. Riboflavin 核黄素

13、B2 核醇ribitol 7，8 二甲基异咯嗪isoalloxazine ringRiboflavin (vitamin B2), is a component of the flavin coenzymes, FAD and FMNSite N1 and site N5 has active double bondrespectively flavin coenzymes: flavin adenine dinucleotide (FAD) flavin mononucleotide (FMN)FAD is an important acceptor of electrons FAD is

14、the oxidized form of the molecule (lacks electrons). FADH2 is the reduced form (carries electrons)FAD and FADH2 function in many oxidation reactionsSuccinate琥珀酸 + FAD(enzyme bound) Fumarate延胡索酸 +FADH2(enzyme bound)FAD is bound covalently to the enzyme protein through a specific histidine residueThe

15、ability of the ring system of riboflavin to exist as asemiquinone allows the flavin coenzymes to accept electrons either singly or in pairsSymptoms include:cracks at corners of mouthhypersensitivity to light怕光skin rash皮疹Riboflavin DeficiencySupports normal vision & skin healthMilk and milk productsM

16、eats Leafy green vegetablesEnriched and whole-grain cerealsLight and irradiation, but not heat, destroy riboflavin Food Sources3. Vit PP 抗癞皮病维生素 VB3烟酸nicotinic acid烟酰胺nicotinamidenicotinamide烟酰胺coenzymes nicotinamide adenine dinucleotide (NAD+)nicotinamide adenine dinucleotide phophate (NADP+ )Niaci

17、n（vitamin PP)Niacin (vitamin PP)Nicotinic acid nicotinamide Can be made from tryptophan色氨酸 ( 60 mg tryptophan make 1 mg niacin)Coenzyme forms : coenzyme I or NAD+ and coenzyme II or NADP+ Part of coenzyme use in energy metabolism Supports health of skin, nervous system, and digestive systemCoenzyme

18、I and IINADH is a carrier of electrons produced in biological oxidations.two formsNADH -reduced form of the molecule (carries electrons)NAD+ -oxidized form of the molecule (lacks electrons)The reduced nucleotides absorb light at 340 nm; the oxidized forms do notNADPH is an electron carrier.Two forms

19、: NADPH -reduced form of the molecule (carries electrons) NADP+ -oxidized form of the molecule (lacks electrons)NADPH is produced - pentose phosphate pathwayIn plants, photosynthesis is another source of NADPH.NADH VS NADPH:NAD+/NADH : favorates electrons to the electron transport system for energy

20、generation 氧化途径（分解代谢）中电子受体NADP+/NADPH :donates electrons to biosynthetic reactions 还原途径（合成代谢）电子供体More than 200 enzymes are known to catalyze reactions by using NAD or NADP as the electron transfer.NAD+, NADP+ VS FAD, FMN, NAD+ NADP+ ，each pair of electrons results 2.5 ATPs FAD FMN ，each pair of elec

21、trons results in 1.5 ATPsPellagra糙皮病、癞皮病 (Occurs in poorly nourished people and alcoholics)Characterized by the 4 DsDiarrhea腹泻Dermatitis皮炎Dementia 痴呆DeathNiacin DeficiencyIn 1937，Frank Strong, D. Wayne Wolley, and ConradElvehjem identified niacin as the curative agent for blacktongue（狗的癞皮病）MilkEggsM

22、eat, fish, poultryWhole grains, enriched breads and cerealsNutsProtein-containing foodsFood Sources of Niacin4. pantothenic acid and Coenzyme A (CoA or CoASH)Pantothenic acid，VB5 遍多酸、辅酶Acoenzyme A - acyl-carrier moietyCoenzyme A结合乙酰基Acetyl-coenzyme A 乙酰基辅酶A, the acyl group is linked to the thiol硫醇 g

23、roup to form an energy-rich thioester硫酯Acetylated form: acyl-CoA, CH3CO-SCoAUnacylated form : CoA-SH.高能键，键能与ATP相当Involved in synthesis of lipids, neurotransmitters, steroid hormones and hemoglobin血红蛋白involved in release of energy from energy-yielding nutrientsPantothenic AcidDeficiencies are rare bu

24、t result in general failure of bodys systemsWidespread through foods meat, fish, poultry家禽肉, whole grain cereals, legumes豆类Destroyed by heatDeficiency and Recommendations5. Vit B6 & Pyridoxal Phosphate (PLP)氨基酸代谢中多种酶的coenzyme吡哆醛吡哆醇吡哆胺pyridine derivatives 吡啶衍生物磷酸吡哆胺磷酸吡哆醛PLPPyridoxal phosphate partici

25、pates in:transaminations 转氨作用,decarboxylations 去碳酸基,numerous modifications of amino acid side chainsHelps convert tryptophan to niacin key role in cognitive development Symptoms include:weaknessIrritability易过敏Insomnia失眠greasy dermatitis脂溢性皮炎Convulsions抽搐weakened immune responsegrowth failureB6 Defic

26、iencyProtein-rich foods - meat, fish, poultry家禽肉PotatoesLeafy green vegetablesSome fruits, e.g., bananaB6 is lost when foods are heatedFood Sources6. Vitamin B12The presence of cobalt and amide nitrogens -the name cobamides or cobalamins 钴胺素,钴胺酰胺 The metal cobalt is coordinated corrin ring咕啉环, The c

27、yanide 氰化物attached to the cobalt 核苷酸还原成脱氧核苷酸 5-脱氧腺苷钴胺素辅酶 isomerization异构化 甲基钴胺素 methyl group transferAbout 15 different B12-requiring reactions are knownThe synthesis of methionine甲硫氨酸 from homocysteine高半胱氨酸 B12-requiring reactions involve :(1) methyl group transfer(2)核苷酸还原成脱氧核苷酸by a ribonucleotide

28、reductase of Lactobacillus 乳酸菌.(3) isomerizations：exchange a carbon-bound hydrogenwith another carbon-bound functional group甲基丙二酰-CoAB12 and folate depend on each other for activationHelps maintain the protecting sheath around nerve cellsMay influence cells that build bone tissueHelps in metabolism

29、of some AA e.g., regeneration of methionine in cellVitamin B12 (Cobalamin)B12 is bound to dietary protein released by HCL & pepsin胃蛋白酶B12 absorption requires intrinsic factor内在因子compound - a glycoprotein synthesized in the stomach wallattaches to the vitaminthe complex passes into small intestine an

30、d is absorbed into blood streamGenetic trait resulting in a lack of intrinsic factor, often begins in mid-adulthoodInhibits normal absorption of dietary B12Develop deficiency symptoms-pernicious anemiaVitamin B12 injections necessaryVitamin B12Pernicious anemiacharacterized by large, immature red bl

31、ood cells and damage to nervous systemOther symptoms include:fatiguedamaged nerve sheaths creeping paralysis运动共济失调 general malfunction of nerves and musclesnerve damage is serious and irreversibleB12 DeficiencyOnly in foods of animal originSerious problem for strict vegetarians or vegansneed to eat

32、B12 fortified foods OR take supplementsFood SourcesActs as a coenzyme : carries CO2 in TCA cycleImportant: in gluconeogenesis, FA syn., & oxidation of some FA & AANeeded in small amounts 7. BiotincarboxylaseEnzymes containing biotin:Acetyl CoA carboxylase乙酰辅酶A羧化酶Acetyl-CoA +ATP+HCO3-Malonyl-CoA丙二酸单酰

33、辅酶A +ADP+Pi+H+Pyruvate carboxylasePyruvate+HCO3-+ATP Oxaloacetate草酰乙酸+ADP+Pi+H+Rare as biotin is widespread in foodsSeen when raw egg whites givenThe protein avidin in egg whites binds biotinScaly dermatitis皮炎, hair loss, loss of appetite, depressionBiotin deficiencyAvidin- biotin (affinity chromato

34、graphy )8. Folic Acid (Pteroylglutamic acid碟酰谷氨酸)Folate active forms(tetrahydrofolate)Dihydrofolate reductase(DHFR)NADPH specific enzymeTetrahydrofolate-generation and utilization of single-carbonMethyl 甲基Methylene 亚甲基Formyl 甲酸基N5, N10 or bothsingle carbonPrimary coenzyme form - tetrahydrofolate (TH

35、F) part of enzyme complex required for metabolism of single-carbon compounds Required for making of new cellsHelps synthesize nucleotides Helps convert vitamin B12 to its active formFolateFolic acid deficiencyDNA synthesisCell division is slow, volume increaseMegaloblastic anemia 巨红细胞性贫血Activity of

36、DHFR is blocked by folate analogsAminopterin 氨蝶呤Amethopterin 氨甲喋呤 抗肿瘤药物嘌呤、胸腺嘧啶合成肿瘤生长Deficiency first affects cells which divide and multiply rapidlyBlood cells and GI tract 胃肠道cellsResults in:Macrocytic or megaloblastic巨幼红细胞anemia Abnormal digestive functionNeural tube defectsFolate DeficiencyGreen

37、leafy vegetablesFresh, uncooked vegetables and fruitEggsLegumes豆类, including peanutsheat and oxidation can destroy folate activity Food Sources9. Lipoic acid 硫辛酸闭环二硫化物形式开环还原形式Lipoic acid+ Lys 硫辛酰胺复合物lipoamideAn amide bond linking the carboxyl group of lipoic acid to a lysine amino group of the enzymeLipoateTwo thiol groups-reversible oxidation to a disulfide bond(-S-S-)Electron hydrogen carrierAcyl carrierAscorbic Acidmeans “no scurvy” acidRole as an antioxidantprotects water