《生物化学biochemistry》双语课件ppt 06 维生素vitamin and coenzyme

Chapter 6 Vitamin and Coenzyme Date1 VitaminsVitamins are organic molecules that are essential to the biological processes of higher organisms, but cannot be synthesized by these organisms. Fat-soluble: vitamins A, D, E, and K Water-soluble: B complex vitamins，lipoic acid and vitamin C. Date2 wVitamin functions: Coenzymes in catalyzed reactions (derivates of vitamin Bs) Some vitamins are considered as hormones (vitamins A they are either unmodified or regenerated. Each kind of coenzyme has a particular chemical function. Some are oxidation/reduction agents, some facilitate group transfers, and so forth. The number of important coenzymes is limited, but each of them may be associated with many different enzymes. Date16 interconverting UDP-glucose and UDP-galactose The mechanism : the hydroxyl at position 4 is changed in stereochemical orientation involves oxidation of the hydroxyl to a carbonyl羰基as an intermediate state. Carbonyl intermediate - excellent intermediate state for interconversion of the sugars NAD+ and NADH never leave the enzyme, they are reduced and reoxidized in a cyclic fashion, providing a temporary resting place for electrons and the hydrogen from the substrate. Date17 腺苷钴氨素甲基钴氨素 Date18 1. 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pyrimidine 抗脚气病维生素 two heterocyclic rings Date19 Mechanism of action TPP ： thiazole is the reactive moiety , carbanion 负碳离子. Carbanion can attack the carbonyl carbon of a-keto acids, such as pyruvate, giving an addition compound TPP is used as a coenzyme for all decarboxylations of -keto acids thiamine (Vitamin B1) + ATPpyrophosphate groupTPP +AMP a Date20 羟乙基-TPP Date21 1. Carbanion attack on the carbonyl- carbon 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 in forming a resonance-stabilized eneamine. 3. Protonation of the eneamine to form an active acetaldehyde called hydroxyethyl-TPP. 4. The decarboxylated compound is released, yielding free TPP. 5. Carbanion formation 羟乙基-TPP Date22 pyruvate decarboxylase 丙酮酸脱羧酶, pyruvate dehydrogenase丙酮酸脱氢酶, branched chain a-keto acid dehydrogenase glutarate dehydrogenase酮戊二酸脱氢酶 Transketolase 转羟乙醛酶,转酮醇酶., Some enzymes that use TPP : Date23 维生素B1缺乏,糖代谢受阻,丙酮酸积累 血、尿、脑组织丙酮酸含量增多，出现多 发性神经炎，皮肤麻木，心力衰竭，肌肉 萎缩。下肢浮肿等 脚气病 Date24 nicotinamide烟碱coenzymes nicotinamide adenine dinucleotide (NAD+) nicotinamide adenine dinucleotide phophate (NADP+ ) 2. Vit PP 抗癞皮病维生素 烟酸nicotinic acid 烟碱nicotinamide Date25 NADH is a carrier of electrons produced in biological oxidations. two forms NADH -reduced form of the molecule (carries electrons) NAD+ -oxidized form of the molecule (lacks electrons) Date26 NADPH is an electron carrier. Two forms: NADPH -reduced form of the molecule (carries electrons) NADP+ -oxidized form of the molecule (lacks electrons) NADPH is produced - pentose phosphate pathway In plants, photosynthesis is another source of NADPH. Date27 NADH VS NADPH NAD+/NADH : donates electrons to the electron transport system for energy 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 Date28 3. Riboflavin 核黄素 核醇ribitol 7，8 二甲基异咯嗪 isoalloxazine ring Riboflavin (vitamin B2), is a component of the flavin coenzymes, FAD and FMN Date29 Site N1 and site N5 has active double bond respectively Date30 FAD is an important acceptor of electrons FAD is the oxidized form of the molecule (lacks electrons). FADH2 is the reduced form (carries electrons) Flavin coenzymes: flavin adenine dinucleotide (FAD) flavin mononucleotide (FMN) Date31 FAD and FADH2 function in many oxidation reactions Succinate + FAD(enzyme bound) Fumarate + FADH2(enzyme bound) FAD is bound covalently to the enzyme protein through a specific histidine residue Date32 The ability of the ring system of riboflavin to exist as a semiquinone allows the flavin coenzymes to accept electrons either singly or in pairs Date33 Common acceptors of electrons include the FAD, FMN, NAD+, NADP+ NAD+, NADP+ can accept electrons in pairs, each pair of electrons from NADH results 2.5 ATPs FAD and FMN can also accept single electrons via formation of a semiquinone intermediate, each pair of electrons donated by FADH2 results in 1.5 ATPs Date34 4. Pantothenic acid and Coenzyme A (CoA or CoASH) Pantothenic acid coenzyme A - acyl-carrier moiety Date35 -Mercaptoethylamine巯基乙胺- acyl groups are attached Date36 3,5-ADP A free thiol is the functionally significant part of the coenzyme molecule The rest of the molecule provides enzyme binding sites 3,5-ADP: 识别部位, 增加CoA亲和性和专一性 Date37 acylated derivatives, such as acetyl-coenzyme A, the acyl group is linked to the thiol group to form an energy-rich thioester the acylated forms of coenzyme A : acyl - CoA, CH3CO - SCoA the unacylated form : CoA-SH. Date38 energy-rich nature of thioesters VS ordinary esters Date39 Common metabolic reactions involving Coenzyme A are shown below. 1. Acetate+ CoASH + ATP Acetyl-CoA + AMP+ PPi (catalyzed by Acetate Thiokinase硫激酶). 2. Pyruvate + NAD+ + CoASH Acetyl-CoA + NADH + CO2 (catalyzed by Pyruvate Dehydrogenase) 3. 3-Ketoacyl-CoA + CoASH Acyl-CoA (less 2 carbons) + Acetyl- CoA (catalyzed by Thiolase硫解酶). Date40 4. Malonyl-CoA + ACP Malonyl-ACP + CoASH(catalyzed by Malonyl-CoA-ACP Transacylase) 5. Acetyl-CoA + ACP Acetyl-ACP+ CoASH (catalyzed by Acetyl- CoA-ACP Transacylase) 6. Acyl-CoA + Carnitine Acyl-Carnitine + CoASH (catalyzed by Carnitine Acyltransferase I) 7. Acyl-Carnitine + CoASH Acyl-CoA+ Carnitine (catalyzed by Carnitine Acyltransferase II) 肉(毒)碱 Date41 5. Vit B6 & Pyridoxal Phosphate (PLP) Vit B6 吡哆醛 嘧啶衍生物 吡哆醇 吡哆胺 活性形式：磷酸吡哆醛（PLP) 氨基酸代谢中多种酶的coenzyme 磷酸吡哆胺 Date42 Pyridoxal phosphate participates in transaminations 转氨作用, decarboxylations 去碳酸基, numerous modifications of amino acid side chains Date43 PLP-containing enzymes function: Schiff base between the amino acid and coenzyme A cation (a metal or a proton) is essential to bridge the phenolate ion of the coenzyme and the imino 亚氨基的nitrogen of the amino acid. This bridging maintains the planarity of the structure, essential for catalysis. Date44 a quinoid 醌型structure Depending on the bond labilized 使 不稳定, formation of the aldimine 醛亚胺can lead to a transamination , to decarboxylation, to racemization, or to numerous side chain modifications Date45 6. Vitamin B12 The presence of cobalt and amide nitrogens - the name cobamides or cobalamins 钴胺素,钴胺酰胺 Date46 The metal cobalt is coordinated corrin ring咕啉环, The cyanide 氰化物 attached to the cobalt 辅酶： 5脱氧腺苷钴胺素 甲基钴胺素 About 15 different B12-requiring reactions are known 核苷酸还原成脱氧核苷酸 isomerizations methyl group transfer Date47 B12 coenzymes methyl group 5-adenosyl moiety CN linked to cobalt the first known organometallics vitamin in metabolism Date48 the synthesis of methionine 甲硫氨酸from homocysteine高半 胱氨酸 Date49 B12-requiring reactions involve : (1) methyl group transfer (2)核苷酸还原成脱氧核苷酸 by a ribonucleotide reductase of Lactobacillus 乳酸菌. (3) isomerizations：exchange a carbon-bound hydrogen with another carbon-bound functional group 甲基丙二酰-CoA Date50 7. Biotin 噻吩环 双环化合物 尿素 戊酸 Biotin Date51 Biotin is a vitamin and a coenzyme linked covalently to carboxylase enzymes through the - amino nitrogen of lysine 生物胞素复合物 associated with enzymes performing carboxylation reactions Date52 Enzymes containing biotin： acetyl CoA carboxylase Acetyl-CoA + ATP + HCO3- Malonyl-CoA丙二酸单酰 SCoA + ADP + Pi + H+ pyruvate carboxylase Pyruvate+ HCO3- + ATP Oxaloacetate + ADP + Pi + H+ Carbamoyl 氨基甲酰phosphate synthetase II Glutamine+ ATP + HCO3- Glutamate + Carbamoyl Phosphate+ ADP Date53 Biotin - vabundant in many foods and is synthesized by intestinal bacteria vdeficiency is rare, but caused by a diet rich in raw eggs vEgg whites contain a large amount of the protein avidin (Mr 70,000), which binds very tightly to biotin and prevents its absorption in the intestine. vThe avidin of egg whites may be a defense mechanism for the potential chick embryo, inhibiting the growth of bacteria. vWhen eggs are cooked, avidin is denatured (and thereby inactivated) along with all other egg white proteins. Avidin- biotin (A protein covalently bound ) affinity chromatography Date54 碟酸 碟酰谷氨酸 6甲基碟啶 对氨基苯甲酸 8. Folic Acid (Pteroylglutamic acid碟酰谷氨酸) 吡嗪 Date55 Folic acid is formed from three distinct moieties: (1) 6-methylpterin 6甲基喋啶 (2) p-aminobenzoic acid (PABA), 对氨基苯(甲)酸 (3) glutamic acid 3-8 or more glutamate residues per molecule of vitamin Date56 folate - active forms (tetrahydrofolate) dihydrofolate reductase (DHFR) -NADPH-specific enzyme Date57 tetrahydrofolate -generation and utilization of single-carbon methyl甲基, methylene 亚甲基, formyl甲酸基 N5, N10 or both - single-carbon Date58 Date59 Activity of DHFR is blocked by folate analogs aminopterin 氨碟呤 amethopterin氨甲碟呤 抗肿瘤药物 嘌呤&胸腺嘧啶 肿瘤生长 氨碟呤氨甲碟呤 Date60 Folic acid deficiency DNA synthesis Cell division is slow, volume increase megaloblastic anemia巨红细胞性贫血 Date61 9. lipoic acid 闭环二硫化物形式 开环还原形式 Lipoic acid+Lys 硫辛酰胺复合物lipoamide an amide bond linking the carboxyl group of lipoic acid to a lysine -amino group of the enzyme. Date62 Lipoic acid in amide linkage with a Lys residue Date63 Lipoate Two thiol groups - reversible oxidation to a disulfide bond (-S-S-) electron hydrogen carrier acyl carrier Date64 Date65 10. Vitamin C (Ascorbic Acid) a water-soluble enzyme acidic acts as a potent antioxidant, protecting against damage by reactive oxygen species (2,3 site - OH) L- ascorbic Acid dehydro-ascorbate 2 Date66 Antioxidants such as vitamin A, vitamin C, and vitamin E provide protection against oxidative damage from reactive oxygen species, such as superoxides, hydroxyl radicals, hydrogen peroxide. Date67 a role in making cross links between amino acids in collagen胶原蛋白 Vitamin C Collagen fibers- form the matrix, or cement, material in bone, on which the mineral constituents precipitate. an important constituent of tendons and skin Date68 Collagen : widespread modification proline to hydroxyproline lysine to hydroxylysine The hydroxylation羟基化作用 reactions in collagen involve vitamin C 羟化酶维持活性所必需 的辅因子 Date69 prolyl 4-hydroxylase reaction Date70 1000 residues in length 3-fold helical left-hand helices 3.3 residues/turn right-hand sense, with hydrogen bonds extending between the chains. GlyXY X and Y are generally Pro or 4-Hyp Date71 hydrogen bonds between chains in the triple helix : amide protons- carbonyl oxygens, the OH groups of hy