生物化學(xué)教學(xué)課件：蛋白質(zhì)降解及氨基酸分解代謝

1、淮南八公山豆腐制作Department of Biochemistry, University of Colorado(200207-200711)CytokinesisMetaphaseAnaphaseNeuron diversity, dipoid and aneuploidProtein degradation, Amino Acid Metablism：Catablism and Biosynthesis of Amino Acids Nitogen FixationDegradation and Biosynthesis of NucleotidesMetabolism Regula

2、tionLehninger Principles of Biochemistry, 4th editionTextbook of biochemistry with clinical correlations1 Protein digestion2 Protein degradation Lysosome medidated-degradation Autophagy Ubiquitin-mediated3 Amino acid catablism4 Amino acid synthesisProtein degradation, Amino Acid MetablismThe signifi

3、cance of amino acid1. Cells / tissues growing, renewing and mendingProtein Degradation/ Amino Acid MetablismThe significance of amino acid2. Take part in physiological activities3. Oxidation and supply energy70kg的人，每天有400g的protein發(fā)生變化：400g發(fā)生再循環(huán)；100g氧化講解提供能量4. Nitrogen balanceBefore we get on amino a

4、cid metablism:1. Breakdown of dietary proteins2. Protein degradation in cellsProtein breakdown starts at stomachOptimal pH1.52.5，Low specificityProduce small peptide and free amino acids pepsinogen胃蛋白酶原+ Small PeptideHCl、PepsinPepsinBreakdown of dietary proteins Both are generated in stomach !主細(xì)胞（ch

5、ief cell）：胃酶細(xì)胞，zymogenic cell壁細(xì)胞（parietal cell）：泌酸細(xì)胞，oxyntic cell泌酸細(xì)胞：較大，多呈圓錐形。核圓而深染，居中；胞質(zhì)呈均質(zhì)而明顯的嗜酸性。胃酸: 雙刃劍，過(guò)少或缺乏時(shí)，消化不良; 分泌過(guò)多,對(duì)胃和十二指腸黏膜發(fā)生侵襲作用，導(dǎo)致潰瘍，穿孔、出血等；Chief cells secrets pepsinogen，典型蛋白質(zhì)分泌細(xì)胞的結(jié)構(gòu)特點(diǎn)：柱狀，核圓形；胞質(zhì)基部呈強(qiáng)嗜堿性，頂部充滿酶原顆粒。細(xì)胞核周有大量粗面內(nèi)質(zhì)網(wǎng)與發(fā)達(dá)的高爾基復(fù)合體。Cholecystokininkolsstkann ( 縮膽囊素) stimulates secre

6、tion of several pancreatic enzymes (胰腺酶）with activity optima at pH 7 - 8.Pancreas exocrine cells :Trypsinogen(胰蛋白酶原）Chymotrypsinogen（糜蛋白酶原）Procarboxypeptidases A, B 羧肽酶The digestion of proteins in the small intestine（小腸）.Enterokinase腸激酶 : produced by cells of the duodenum du:di:nm （十二指腸）絲氨酸蛋白酶（Serin

7、e protease)家族:利用Ser殘基來(lái)催化水解肽鍵絲氨酸蛋白酶家族：Trypsin，Chymotrypsin，Elastase，Carboxypeptidases只有一個(gè)絲氨酸殘基催化肽鍵斷裂，Ser-His-Asp形成催化三聯(lián)體其它蛋白酶家族：半關(guān)氨酸蛋白酶天冬氨酸蛋白酶金屬離子蛋白酶絲氨酸蛋白酶1 絲氨酸蛋白激酶通過(guò)有限水解，調(diào)控（激活）絲氨酸蛋白水解酶；2 絲氨酸蛋白水解酶有相似的結(jié)構(gòu)和功能；在肽鍵水解過(guò)程中表現(xiàn)高特異性；3 調(diào)控血液凝固，補(bǔ)提激活，受精，激素生產(chǎn)等許多生理過(guò)程；4 動(dòng)物/植物中存在天然抑制劑；5 調(diào)控缺乏或異常導(dǎo)致蛋白質(zhì)消化自溶，從而發(fā)生疾病，如血友病、癌癥轉(zhuǎn)移等

8、。Synthesis of the enzymes as inactive precursors-zymogen(酶原或前酶）:1 Protects the exocrine cells from destructive proteolytic attack. 2 Transportation3 Allow RegulationElaborate mechanism for getting active digestive enzymes.Protein Digestion Proteolytic enzymes of pancreatic juiceEndopeptidasesExopept

9、idasesTrypsin : Arg, Lys (C)Chymotrypsin : Tyr, Trp, Phe, Met, Leu (C)Elastase: Ala, Gly, Ser (C)carboxypeptidaseaminopeptidaseCleavage sites and substrates of proteasesMARTKQTARKSTGGKAPRKQLATKAARKSAPSTGCleavage sites and substrates of proteases一They hydrolyze the peptides very efficiently.In humans

10、, most globular proteins from animal sources are almost completely hydrolyzed to amino acids in the gastrointestinal tract, some proteins, such as keratin(角蛋白）are only partly digested. The protein content of some plant foods is protected against breakdown by indigestible cellulose husks（外殼）.Absorpti

11、on of free amino acids Trypsin and Protease in Cell CultureTrypsin used for protein sequencing Enterokinase used in protein purification 腸激酶酶切位點(diǎn)DDDDK 基于MS/MS的蛋白質(zhì)序列和修飾鑒定Liquid chromatography-coupled mass spectrometery(LC-MS)Tryspin digestionA disease caused by obstruction of the normal pathway by whi

12、ch pancreatic secretions enter the intestine. The enzymogens of the proteolytic enzymes are converted to their catalytically active forms prematurely, inside the pancreatic cells, and attack the pancreatic tissue itself. This causes excruciating kskru:etl pain and damage to the organ that can prove

13、fatal. Acute pancreatitis and Protease(急性胰腺炎）Questions：1 蛋白酶水解的是什么化學(xué)鍵？2 人體消化道內(nèi)有哪些蛋白酶? 3 酶以酶原的形式存在有什么意義？Protein Degradation in CellLife-span of protein in cell：Insulin(胰島素)：1hrhemoglobin、Histone：few monthsLens, neuron：lifelongMost of proteins: a few daysProtein degradation in cells:1 dynamic turnover

14、 :2 apoptosis:Protein degradation in cells:1 dynamic turnover :2 apoptosis:3 Energy-providing:機(jī)體中大多數(shù)的蛋白和氨基酸存在與骨骼肌中，機(jī)體運(yùn)耗能時(shí)，這些蛋白質(zhì)被降解為氨基酸，用于產(chǎn)能和糖異生。4 Branch chain amino acids are preferred for energy-providing.5 Protein degradation is occurring everywhere in the body, muscle is the major location of pro

15、tein degradation.Two major systems for the turnover of cellular proteins:Lysosomes and Ubiquitin-mediated protein degradationProtein Degradation in Cell1 Lysosomal hydrolasesexhibit acidic pH optimal.2 Lost activity if leaked into cytosol.3 Cathepsin 組織蛋白酶家族Low specificityLysosomal Degradation Pathw

16、ayProteinsA. EndocytosedB. Cytosolic C. Organelles by autophagy溶酶體貯積?。夯蛲蛔冎氯苊阁w酸性水解酶缺陷痛風(fēng)：溶酶體破裂大隅良典Yoshinori Ohsumi，2016年諾貝爾生物學(xué)和醫(yī)學(xué)獎(jiǎng), Prize motivation: for his discoveries of mechanisms for autophagyAutophageConsequences of autophagy：survival or cell deathConsequences of autophagy：survival or cell deat

17、h自噬作用是細(xì)胞內(nèi)的溶酶體降解自身細(xì)胞器和其他大分子的過(guò)程。形態(tài)學(xué)特征：電鏡下可觀察到胞質(zhì)中有大量包裹著細(xì)胞漿和細(xì)胞器的空泡結(jié)構(gòu)，稱作自噬泡。主要過(guò)程：自噬泡形成，與溶酶體發(fā)生融合，自噬泡所包裹著的待降解物質(zhì)進(jìn)入溶酶體，在各種酶的作用下分解成氨基酸和核苷酸等，并進(jìn)入三羧酸循環(huán)，產(chǎn)生小分子和能量ATP-再被細(xì)胞所利用Autophagic cell death and apoptosis細(xì)胞自噬與細(xì)胞凋亡之間似乎存在著某種調(diào)控機(jī)制，可調(diào)節(jié)二者的相互拮抗或促進(jìn)相互替換Autophagy and drug resistence(細(xì)胞耐藥性)細(xì)胞自噬對(duì)人類健康是一把雙刃劍。Ubiquitin pathw

18、ayUbiquitinProteasomeE3 ligase(Cullin-RING complex)Protein Degradation System in CellWhat is Ubiquitin and Ubiquitylation?Human Ub: MQIFKVTLTGKTITLEVEPNDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLRGGYeast Ub: MQIFKVTLTGKTITLEVESSDTIDNVKSKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG蛋白酶體（P

19、roteasome）19S lid19S lid20S coreUbiquitination Ub activating enzyme(Uba) Ub conjugating enzyme(Ubc) E3- Ub Ligase-SubUbiquitin pathwayE1-S-UbE2-S-UbE3substratesUbMono-ubiquitinationChange：protein conformation,Localization, interactionPolyubiquitinationUbUbUbUbsubstratesProteosomeDegradationE1- Ub ac

20、tivating enzyme(Uba)Uses ATPAMP+PPi to form thioester bond between its sulfhydryl group and the terminal carboxylate group of UBE2- Ub conjugating enzyme(Ubc):Accepts activated UBE3- Ub Ligase: Catalyzes transfer of UB from E2 to -amino group of lysine on target protein forming an isopeptide bond異肽鍵

21、ATP肽鍵和異肽鍵substrateUbMQIFKVTLTGKTITLEVEPNDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLRGG蛋白質(zhì)泛素化降解途徑7要素Control of p53 by ubiquitylationChromatin structure Transcriptional regulation.Turn over of oncogene productsCell cycle controlRegulation of DNA repair responseApoptosisEndocytosis一般了解（不考）Con

22、trol of Cell Cycle Progression by Distinct E3 ComplexesAnaphase-Promoting ComplexTwo families of E3 ubiquitin ligases一般了解（不考）一般了解（不考）The Nobel Prize in Chemistry, 2004“for the discovery of ubiquitin-mediated protein degradation”Avram HershkoIrwin RoseAaron CiechanoverQuestions細(xì)胞內(nèi)主要的蛋白質(zhì)降解體系是什么？細(xì)胞內(nèi)主要的

23、蛋白質(zhì)降解體系各有什么特點(diǎn)?泛素化降解的要素有哪些？消化道內(nèi)有哪些蛋白酶參與了蛋白質(zhì)的消化？Amino Acid PoolAmino acid metabolism Deamination（脫氨） Transamination（轉(zhuǎn)氨作用） Urea cycle（尿素循環(huán)） Pyruvate group a Ketoglutarate group Succinyl-CoA group Oxaloacetate group Fumarate / oxaloacetate group Alanine / acetoacetate group Acetyl-CoA / acetoacetate gro

24、up Decarboxylation1. Deamination of AAstransamination oxidative deaminationunion deamination Important in the diagnosis of heart and liver damage caused by heart attack, drug toxicity, or infection. After a tissue/organ damage, a variety of enzymes, including these aminotransferases, leak from the i

25、njured tissue cells into the bloodstream. Assays for Tissue Damage by Analyses of amino-transferase activities in blood serumTransamination(轉(zhuǎn)氨作用）1 An amino group is transferred to an -keto acid, with formation of the corresponding amino acid and another -keto acid.2 Usually occurs in amino acid degr

26、adation3 Transamination is reversible, however，transamination of essential amino acid is unidirectional, Ser, Lys and Pro cannot be transaminated.5 Key roles of Glu and -keto glutarate in transaminationTransamination4 -keto acid produced in transamination can be intermediator for TCA 6 Only the - am

27、ino group of Glu enters Urea cycleALT: Alanine aminotransferase (in liver) 丙氨酸氨基轉(zhuǎn)移酶，also called glutamate-pyruvate transaminase（谷丙轉(zhuǎn)氨酶）, GPTAST: Aspartate aminotransferase (in heart) ，also called glutamate-oxaloacetate transaminase（谷草轉(zhuǎn)氨酶）, GOTTwo important transaminases:嗜酒如命進(jìn)食高蛋白補(bǔ)品服用某些藥物肝?。ǜ窝?、肝損傷)腎病(

28、谷氨酰轉(zhuǎn)肽酶)/uniprot/P24298Function ExpressionActivityCellular Localization DomainModificationStructureRegulationCofactorTransamination-needs coenzyme pyridoxal phosphate（磷酸吡哆醛， B6）1 Covalent ligated to enzyme2 Interaction with enzyme3 Schiffs baseVitamine B6亞胺Transamination need coenzyme pyridoxal phosp

29、hate(PLP)ALL Aminotransferases identified so far use pyrodoxal phosphate as coenzyme. Pyridoxamine phosphate(PMP)(2) Oxidative deaminationGlutamate Releases Its Amino Group as Ammonia in the Liver1 In hepatocytes mitochondria, 2 Glutamate undergoes oxidative deamination 3 Catalyzed by L-glutamate de

30、hydrogenase4 Produces free ammonia5 Produces NADH 6 Required for Urea Cycle7 The enzyme is strictly regulated How and Why？(3) Union deaminationAlanine + -ketoglutaratePyruvate + glutamateGlutamate + NAD+ + H2O-ketoglutarate + NADH + NH4+Net Reaction: Alanine + NAD+ + H2Opyruvate + NADH + NH4+The com

31、bined action of an aminotransferase and glutamate dehydrogenaseTransaminase, glutamate dehydrogenase.(3) Purine nucleotide cycle (in muscle)草酰乙酸腺苷酰琥珀酸蘋果酸延胡索酸腺苷酸次黃苷酸1. Sources: Deamination of AAs-main source Catabolism of other nitrogen containing compoundsAmmonia (NH3) :Source and outlet2. Outlets:(

32、1) Formation of urea in liver(2) Formation of Gln(3) Synthesis of AA(4) Excrete in urineMetabolism of Ammoniamost vertebratesbirds & reptilesfish & other aquatic vertebratesTransportation of NH31 Glucose Alanine cycle2 Transportation of ammonia by Gln Ammonia Is Toxic to Animals!Ammonia is converted

33、 to Urea cycle in liver cells.Life-span of protein in cell：Insulin 胰島素：1hrhemoglobin、Histone：few monthsLens, neuron：lifelongMost of proteins: a few daysProtein degradation in cells:1 dynamic turnover :2 apoptosis:3 Energy-providing:機(jī)體中大多數(shù)的蛋白和氨基酸存在與骨骼肌中，機(jī)體運(yùn)耗能時(shí)，這些蛋白質(zhì)被降解為氨基酸，用于產(chǎn)能和糖異生。4 Branch chain ami

34、no acids are preferred for energy-providing.5 Protein degradation is occurring everywhere in the body, muscle is the major location of protein degradation.1 Glucose-Alanine CycleAlanine Transports Ammonia fromSkeletal Muscles to the Liver2. Transportation of ammonia by GlnExcess ammonia in tissues i

35、s added to glutamate to form glutamine, catalyzed by glutamine synthetase(谷氨酰胺合成酶） After transport in the bloodstream,the glutamine enters the liver and NH4 is liberated in mitochondria by the enzyme glutaminase（谷氨氨酰胺酶） blood circulationliver otherorgans musclekidneyureaglucose alanine cycleGlutamin

36、ase丙氨酸：NeutralNon-polarityNon-toxicEasily transported through membraneGlutamine synthetaseFormation of urea1. Site: liver (mitochondria and cytosol)2. Process - ornithine cycleUrea Is Produced from Ammonia in Five Enzymatic Steps(氨、瓜、精琥、精、尿）Hans CrebPhospho-carbonateHydrogencarbonateCarbamateCarbamo

37、yl-phosphateFormation of Carbamoylphosphateby Carbamoylphosphate Synthetase I Formation of carbamoyl phosphate（氨甲酰磷酸）in mitochondria+2ADP+Pi2ATP+CO2+NH3+H2OH2N-C-PO1 The 2 N of urea : NH3 and Asp.2 Starts/ends up with: ornithine3 NH3, CO2 form caramoyl phosphate,4 Citrulline formation,5 Incorporatio

38、n of Asp.6 Energy consuming: One urea 3ATP, 4 P7 Needs 5 enzymes：carbamoyl phosphate synthetase ornithine carbamoyl transferase, OCTArgininosuccinate SynthetaseArgininosuccinaseArginase8 Rate limiting :1st step9 mitochondrianl vs cytosolUrea formation:Regulation of urea synthesisActivation of the ur

39、ea cycle by N-acetyl-glutamateN-acetyl-glutamate synthetase IRegulation of urea synthesisEnergy consuming: one urea will costs 4 PCarbamoylphasphate synthetase ISubstrate activation/inductionResponsive to concentration of ammonia /amino acid in liverProtein-rich dietary Starvation Aspartate（天冬氨酸） Fu

40、marate(延胡素酸）Genetic Defects in the Urea Cycle -Life-ThreateningTotal lack of any Urea Cycle enzyme is lethal.Hyperammonemia - elevated NH3 in blood. Elevated NH3 is toxic, especially to the brain. Severe mental retardation resulted.Control the protein/amino acid intakeRemove the excessive NH3/amino

41、acidsAdd intermediates of Urea cycle一般了解（不考）Tetrahydrofolic acid (FH4) and one carbon unitOne carbon units are produced in catablite of aa and carried by FH4. One carbon units are substance for synthesis of nucleic acid.In great need of new-born蝶啶對(duì)氨基苯甲酸GlutamatePurine ring N5 , N10 of FH4 participat

42、e in the transfer of one carbon units. Analog of FH4 as drug for anti-bacterial蝶啶對(duì)氨基苯甲酸谷氨酸Formation of one carbon unit(1) SerN5,N10-CH2-FH4 (2) GlyN5,N10-CH2-FH4甘氨酸剪切一般了解（不考） (3) His N5-CH=NHFH4一般了解（不考）(4) TrpN10-CHOFH4一般了解（不考）支鏈氨基酸的起始途徑是相同的：BCAA aminotransferases 同工酶Branched keto acidsDehydrogenase

43、1 BCAA aminotransferases are richer in muscle；2 Fasting induces the activity of these enzymes in muscle, but not those in liver;3 BCAA aminotransferases with higher activity locate in liver after dinner.支鏈氨基酸分解代謝酶缺乏并不多見，一旦發(fā)生可造成酸中毒；支鏈酮酸脫氫酶復(fù)合體活性缺失導(dǎo)致楓樹蜜汁尿?。耗蛞壕哂刑厥獾臈鳂涿壑瓪馕?，伴隨酸中毒，智力遲緩和短壽。限制膳食治療！Tyrosine fo

44、rmationfrom phenylalanine(Monooxygenase reaction,單氧化酶)PhenylKetonuria苯丙酮尿癥Phenylalanine HydroxylaseTyrosine AminotransferaseParahydroxyphenyle pyruvate Di-oxygenase (ascorbate Vc)Homogentisate DioxygenaseMaleyl Acetoacetate IsomaeraseFumaryl Acetoacetasemetaboliteconcentration in urine mmoles/24 hco

45、ntrolpatientphenylalanine0.181.8 6.0phenylpyruvate-1.8 12phenyllactate-1.8 3.3phenylacetate-sign. incr.phenylacetylglutamate0.8 1.2 9Phenylketonuria(苯丙酮尿癥， PKU ）: elevated metabolites in urineNon-functional mutation of the phenylalanine hydroxylase gene. There is no cure for PKU If the condition is

46、left untreated, it can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures. A low-phenylalanine diet. Maintain blood Phe levelsPhenylketonuria (PKU). Tyrosine metablism derivates, parkinson, albinismmelanin褪黑激素血清素腦中的神經(jīng)遞質(zhì)，動(dòng)脈和支氣管平滑肌收縮誘導(dǎo)睡眠，晚間合成松果

47、體，視網(wǎng)膜一般了解（不考）How about a cup of milk before sleep?百憂解，氟西汀，F(xiàn)luoxetine，其藥物形態(tài)為鹽酸氟西?。‵luoxetine hydrochloride），抗憂郁藥，商品名為“百優(yōu)解”或“百憂解”（Prozac）。是一種選擇性5-羥色胺再吸收抑制劑（SSRI），在臨床上用于成人憂郁癥、強(qiáng)迫癥，廣場(chǎng)恐懼癥和神經(jīng)性貪食癥的治療。一般了解（不考）acceptorMethionine metabolismI一般了解（不考）高半胱氨酸甲基受體接受甲基甲硫氨酸腺苷甲硫氨酸Methylatedacceptor高半胱氨酸Cysteine is not

48、an essential amino acid if methionine is availableMethionine metabolismII一般了解（不考）Catabolites of amino acid -KetoglutarateSuccinyl CoA（琥珀）Fumarate延胡索酸OxaloacetatePyruvateAcetyl CoAAcetoacetyl CoAIntermediates of TACPEPGlucoseFatty acidKetone bodies blood circulationliver otherorgans musclekidneyureaQ

49、uestions:1 氨基酸分解進(jìn)入三羧酸循環(huán)之前要先經(jīng)過(guò)什么過(guò)程？2 氨基酸脫氨有哪幾種類型？轉(zhuǎn)氨酶的輔基是什么?3 氨基轉(zhuǎn)運(yùn)有哪二種類型，什么是葡萄糖丙氨酸循環(huán)？4 氨基酸脫下的氨在人體體內(nèi)的主要去路有哪些，最終產(chǎn)物是什么？5 尿素循環(huán)的大概過(guò)程，消耗的能量，尿素中N的來(lái)源是怎樣的?6 一碳單位的載體是什么？ Biosynthesis of Amino Acid and Physiologic Amines？AlanineAsparagineAspartateCysteineGlutamateGlutamineGlycineProlineSerineTyrosineArginine*His

50、tidineIsoleucineLeucineLysineMethioninePhenylalanineThreonineTryptophanValineEssential and Nonessential Amino Acids for Humans Essential Nonessential*Arg is essential in infants and growing children but not in adults. Most bacteria and plants can synthesize all 20 amino acids.AAs that an organism ca

51、nnot synthesize under a given set of conditions are called “essential.” Those that can be synthesized in adequate amounts are “nonessential.”23 Humans can synthesize 10 of the 20 common amino acidsBiosynthetic pathways for AAs:Six families corresponding to their metabolic precursorsa-Ketoglutarate G

52、ives Rise to Glutamate, Glutamine,Proline, Arginine氨濃度很高時(shí)Oxidative deaminationGlutamate Releases Its Amino Group as Ammonia in the Liver1 In hepatocytes mitochondria, 2 Glutamate undergoes oxidative deamination 3 Catalyzed by L-glutamate dehydrogenase4 Produces free ammonia5 Produces NADH 6 Required

53、 for Urea Cycle7 The enzyme is strictly regulatedGlutamate and GlutamineGlutaminaseGlutamine synthetaseProline is a cyclized derivative of glutamate吡咯碄-5-羧酸還原酶吡咯-5-羧酸合成酶合成酶缺乏：Too much pro. in blood白內(nèi)障智力遲鈍皮膚過(guò)彈性脫氫酶缺乏：Too much pro，良性，但是會(huì)誘發(fā)癲癇脫氫酶還原酶Urea cycleAAGluGluCarbamoylphosphateornithinecitrullinec

54、itrullineArgininosuccinateornithinArginineOxaloacetateAAGluAspartate2ADP+Pi2ATP+CO2+NH3+H2O1cytosolmitochondrionNH2-C-NH2OUreaa-ketoglutarateH2N-C-PO2345a-ketoglutaratea-ketoglutarateArginineIn liverArginine synthesis in kidney（no arginase)Serine, Glycine, Are Derived from 3-PhosphoglycerateCysteine

55、 Are Derived from 3-Phosphoglycerate （through serine）Mammals synthesize cysteine from homocysteine(高半胱氨酸） and serine.Homocysteine，Methionine, S-adenosylmethionine,S-adenosylhomocysteine腺苷甲硫氨酸腺苷高半胱氨酸甲硫氨酸高半胱氨酸Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruva

56、teEssential AAs: Methionine, threonine, lysine, isoleucine, valine, leucine Nonessential AAs:AlanineAspartateAsparagineAsparagine is synthesized by amidation of aspartate, with glutamine donating the NH4 .Tyrosine formationfrom phenylalanine(Monooxygenase reaction)Tyrosine is considered a conditiona

57、lly essential amino acid, or as nonessentialLysineMethionine一般了解（不考）IsoleusineLeusineValine一般了解（不考）Main biological route of aromatic ring formation. Ring closure of an aliphatic precursor followed by stepwise addition of double bonds.Synthesis of Tryptophan, Phenylalanine, Tyrosine一般了解（不考）Chorismate

58、 （分支酸）Is a Key Intermediate in the synthesis of Tryptophan, Phenylalanine, and Tyrosine1 An aliphatic precursor :Shikimate2 Stepwise addition of double bonds3 Addition of three more carbons. 一般了解（不考）Chorismate Is a Key Intermediate in the synthesis of Tryptophan, Phenylalanine, and Tyrosine一般了解（不考）C

59、horismate and Prephenate to Phenylalanine, Tyrosine一般了解（不考）Histidine Biosynthesis Uses Precursors of Purine BiosynthesisThe pathway to histidine in all plants and bacteria differs in several respects from other amino acid biosynthetic pathways. Histidine is derived from three precursors: PRPP contri

60、butes five carbons, thepurine ring of ATP contributes a nitrogen and a carbonand glutamine supplies the second ring nitrogen. 一般了解（不考）N-1 of the purine ring is linked to the activated C-1 of the ribose of PRPP; Condensation of ATP and PRPPpurine ring opening that ultimately leaves N-1 and C-2 of ade