Testingand Thinking1. (True/False)The most important contributionof the citric acidcycle to energy metabolism is the extraction of high-energyelectrons during the oxidation of acetyl CoA to CO2.Explain youranswer.2.CellularADPConcentrationControlsATPformationalthoughbothADPandParerequiredforthe synthesisofATP,therateofsynthesisdepends mainlyontheconcentrationofADP,notPi,Why?
1 Testing and Thinking • 1.(True/False) The most important contribution of the citric acid cycle to energy metabolism is the extraction of high-energy electrons during the oxidation of acetyl CoA to CO2 . Explain your answer. • 2. Cellular ADP Concentration Controls ATP formation although both ADP and Pi are required for the synthesis of ATP, the rate of synthesis depends mainly on the concentration of ADP, not Pi ,Why?
Which one of thefollowingwould beexpected toincrease theamount ofATP produced through operation of therespiratory chain and chemiosmosis (shown at right)?A.Increasing the permeability ofthe innermitochondrialmembraneto protons(H+)OutsideofcellB.DecreasingthepHinthe spacebetween theeRinnerandoutermitochondrialmembranesC.Applicationofrespiratoryuncouplers,such asATPSYNTHESISthermogeninR+1HHHighInterATPD.Reducing the supply of NADH +H+concentraticnmombranesynthaseOEHHspaceE.IncreasingtheH+ concentrationintheUSNAmitochondrialmatrixBeDraMitochondrialLowmatrixconcontrationOfH
2 Which one of the following would be expected to increase the amount of ATP produced through operation of the respiratory chain and chemiosmosis (shown at right)? A. Increasing the permeability of the inner mitochondrial membrane to protons (H+) B. Decreasing the pH in the space between the inner and outer mitochondrial membranes C. Application of respiratory uncouplers, such as thermogenin D. Reducing the supply of NADH + H+ E. Increasing the H+ concentration in the mitochondrial matrix
ChoiceBis correct.Decreasing the pH in this spacewould increase the concentration ofH+, resulting in a greater proton-motive force and ultimatelyincreasing ATP output
3 Choice B is correct. Decreasing the pH in this space would increase the concentration of H+, resulting in a greater protonmotive force and ultimately increasing ATP output
protein_sorting游离核糖体合成蛋白质的去向TUTORIALISLOADING翻译后转运-游离核糖体，前导肽
4 protein_sorting 翻译后转运-游离核糖体,前导肽 游离核糖体合成蛋白质的去向
粗面内质网的功能信号肽与蛋白质合成mRNA爱ERurOONH3CompletedNTpolypeptideNH3inEREndoplasmicreticulum(ER)Remainsin ERGolgicomplexPlasma4membraneSecretory vesicieLysosome生COTRANSLATIONALIMPORT
◆ 信号肽与蛋白质合成 粗面内质网的功能
信号肽的特性指导分泌性蛋白在粗面内质网上合成●序列特征15-35个氨基酸残基，其中含有4-12个疏水残基●位置：·N-端突出的一段肽内含信号肽
6 信号肽的特性 ◆指导分泌性蛋白在粗面内质网上合成 ◆序列特征 15-35个氨基酸残基，其中含有4-12个疏水残 基 ◆位置: ●N-端突出的一段肽 ●内含信号肽
早期信号假说（signalhypothesis）1975，Blobel等正式提出信号假说，要点是·合成始于游离核糖体N端信号序列靠自由碰撞与内质网膜接触然后插入内质网的膜蛋白质以祥环形式穿过内质网的膜蛋白的存在方式若信号序列被信号肽酶切除：完全进入腔若是停止转移信号：膜蛋白
7 早期信号假说(signal hypothesis) 1975，Blobel等正式提出信号假说,要点是: ◆合成始于游离核糖体; ◆N端信号序列靠自由碰撞与内质网膜接触, 然后插入内质网的膜; ◆蛋白质以袢环形式穿过内质网的膜; ◆蛋白的存在方式: ●若信号序列被信号肽酶切除:完全进入腔 ●若是停止转移信号: 膜蛋白
20世纪80年代初，发现了信号识别颗粒及其受体指导分泌蛋白在粗面内质网上合成，需要其它因子的协助信号识别颗粒（signalrecognitionparticle，SRP）信号识别颗粒的受体（又称停泊蛋白，dockingprotein，DP)等过程：信号肽一信号识别颗粒一信号识别颗粒的受体一合成20世纪90年代初，Blobel又证明在RER膜上存在允许多肽链穿过的蛋白质通道当带有新生多肽链的核糖体结合到内质网膜时，膜上的蛋白蛋白质转质通道开放，信号肽引导新生肽链穿过这一通道；移完成，核糖体从膜上移走之后，通道关闭
8 ◆指导分泌蛋白在粗面内质网上合成,需要其它因子的协助: ●信号识别颗粒（signal recognition particle，SRP） ●信号识别颗粒的受体（又称停泊蛋白,docking protein， DP）等 ●过程: 信号肽→信号识别颗粒→信号识别颗粒的受体→合 成 20世纪80年代初，发现了信号识别颗粒及其受体。 20世纪90年代初，Blobel又证明在RER膜上存在 允许多肽链穿过的蛋白质通道 当带有新生多肽链的核糖体结合到内质网膜时，膜上的蛋白 质通道开放，信号肽引导新生肽链穿过这一通道；蛋白质转 移完成，核糖体从膜上移走之后，通道关闭
信号学说（signaltheory）要点1、信号肽（由信号密码子编码）2、信号识别颗粒/信号识别颗粒受体3、核糖体受体（核糖体亲和蛋白）蛋白质转运通道/信号肽引导新生肽链穿过通道45、信号肽酶（合成结束后切除信号肽）G.Blobel因此项创见而荣获1999年诺贝尔奖！信号学说信号假说（signalhypothesis）(signaltheory)
9 信号学说 (signal theory)要点 1、信号肽（由信号密码子编码） 2、信号识别颗粒 / 信号识别颗粒受体 3、核糖体受体（核糖体亲和蛋白） 4、蛋白质转运通道 / 信号肽引导新生肽链穿过通道 5、信号肽酶（合成结束后切除信号肽） G. Blobel因此项创见而荣获1999年诺贝尔奖！ 信号假说 (signal hypothesis) 信号学说 (signal theory)
Signal hypothesisSRP displaced and recycledmRNAribosome3'signal-recognitionparticle(SRP)CYTOSOLERsignalsequenceERLUMENongrowingSRPreceptor intranslocationpolypeptideERmembranechannelchain10
10 Signal hypothesis