General Biochemistry I
General Biochemistry I BCHS 3304
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BCHS 330402 General Biochemistry I MonWed 100230 SW102 Juan D Pita Almenar PhD University of Houston Neuroscience Electrophysiology Molecular mechanisms of learning and memory Regulation of neurotransmitter uptake during hippocampal longterm potentiationquot Post doctorate Univ of Texas Impact of plasticity on cerebral corteX neuronal networks Current research Importance of regulation of neurotransmitter uptake in learning and memory and neurological disorders Office Room 358 Houston Science Center Office hours Thu3OO5 00 pm or by appointment Office phone 7137438382 Email jdpitaalcentraluhedu BCHS 330402 General Biochemistry I MonWed 100230 SW102 Catalog Description Nature of the chemical constituents of living organisms including carbohydrates lipids nucleic acids and enzymes Course Objectives Upon completion of this course students will know lAmino acid identity structures properties and functions 2Protein structure and function including hemoglobin 3Enzyme mechanisms and kinetics 4The glycolysis and gluconeogenesis pathways and the citric acid cycle Course content see syllabus BCHS 330402 General Biochemistry I MonWed 400530 SeclOl 3 Exams and a Comprehensive Final See Syllabus Exam 1 Sep 19 Exam II Oct 12 Exam 111 Nov 7 Final Exam Dec 12th 2011 25 pm Grading scale 10090 A 899890 A 889880 B 87980 B 799790 B 789780 C 77970 C 699690 C 689680 D 67960 D and lt 60 F Weekly Homework to be COMPLETED but not turned in The lowest score from one regular exams will be dropped Final Exam score will not be dropped The Exams will be based on the book class notes and homework Those who do the homework honestly and persistently will earn the better grades Group homework and study sections groups of 34 are the best size But each person in a group must pull their own weight Copying the homework and not fully participating cheats yourself You will need to know the material You can not just be familiar with it You will need to study about 23 hours a day Most of the gures used in these class notes were taken from the instructor CD provided with the class textbook Voet Voet and Pratt and notes kindly provided by Dr James Briggs 4 Scantron answer keys to the exams may be placed on Blackboard Scores for the exams will be placed on Blackboard Please take advantage of the tutoring and review services in the Learning Support Services provides tutoring for BCHS 3304 httpWwwlasuheduLSStutoringaspx You MUST attend every lecture Chronic lack of attendance will severely impact your course grade You MUST take ALL exams One of the regular exams can be dropped There are NO make up exams There is NO extra credit FUNDAMENIMS IJF BIDEHEMISIHY f M I I D I O I T l ON life at ha Mnleuulat level W unalqueI Judith B Vunl hmln eWPmH Fundamentals of Biochemistry Thim Eatimm Donald Voet Judith G Voet Charlotte W Pratt STUDENT COMPANION Aki Ei cccccc Wi IIIII wmger Donald Voel Judith G Voet Charlotte w Pratt J r r 5 Me athe MUIBIJIJIHf Laval F rlIlI1I39 JlJVuEt Judith Mum EhmlutteWPmtt Copyright 2008 by John Wihy amp Sons6lnc Chapter 1 Introduction to the Chemistry of Life Biochemistry is the study of the chemistry of life Biochemistry is an interdisciplinary science overlapping with chemistry cell biology genetics immunology microbiology pharmacology and physiology Main issues of Biochemistry 1 What are the chemical and threedimensional structures of biological molecules How do biological molecules interact with each other How does the cell synthesize and degrade biological molecules How is energy conserved and used by the cell What are the mechanisms for organizing biological molecules and the coordinating of their activities 6 How is genetic information stored transmitted and expressed 9599 Living organisms operate Within the same physical laws that apply to physics and chemistry Conservation of mass energy Laws of thermodynamics Laws of chemical kinetics Principles of chemical reactions These physical laws describe several axioms that make up the Molecular Logic of Life These aXioms de ne Energy converted to work Catalytic chemical transformations Assembly of molecules with great complexity from simple subunits CompleX molecules combine to form supra molecular components organelles and finally assemble into a cell Store and pass on instructions for the assembly of all future generations from simple nonliving precursors R Most Abundant Elements Preb1ot1c World the Human Bodyquot Dry Weight Element ol Living matter consists of a small number C 617 of elements I 1 Elemental composition of the human body H 57 Ca 50 o 97 P 33 Trace B F Si V Cr Mn Fe Co Cu K 13 S 10 Zn Se Mo Sn I G 07 Na 07 Mg 03 Most organisms are ca 70 water quotCalculated from Frieden E Sci Am 2271 54 55 1972 2008 John Wiley 81 Sons lncAll rights reserved The earth is ca 46 billion years old Earliest known fossil is ca 35 billion J years old lamentous bacterium Prebiotic World Early atmosphere probably consisted of H20 N2 C02 with small amounts of CH4 NH3 02 and H2 Sparking of a mixture of CH4 NH3 H20 and H2 for 1 week yielded Stanley Miller and Harold Urey Acids formic glycolic lactic propionic acetic succinic aspartic glutamic etc Amino acids glycine alanine aspartic glutamic Others urea sarcosine N methylalanine N methyl urea etc The above experiments were meant to mimic the effects of lightening on the prebiotic atmosphere This has been challenged by some scientists who propose that early biological molecules were created in the dark underwater at hydrothermal vents where heat stable bacteria live today Key Organic Functional Groups Common Functional Groups and Linkages in Biochemistry Compound Name Structurequot FunctionalGroup or Linkage Aminequot RNH2 or R lliHa l RZNH or RZNHZ N or N ammo group R3 or R3NH J Alcohol R0 H OH hydroxyl group J Thiol RSH SH sulfhydryl group Ether R0 R 0 ether linkage 0 Aldehyde R C H C carbonyl group 0 II II Ketone R C R C carbonyl group n i ii Carboxylic acid R c OH or R c o C 0H carboxyl group or i J C 0 carboxylate group J O 0 0 II II II Ester R C OR C O ester linkage R C acyl group if i ii Thioester R C SR C S thioester linkage R c acyl group 39 be the ame w diffeuem bUnue hence bear a positive or negative charge 4 L a r If attached to an atom other than carbon o 2003 John Wiley 3 Sons inc All rights reserved Organic FunctionaI Groups you must know these They will show up time and time again in Biochemistry Note that the charge state of some of the groups above will differ in different environmentsconditions eg COOH and COO NH3 and NH4 H Key Organic Functional Groups cont Common Functional Groups and Linkages in Biochemistry Compound Name Structure Functional Group or Linkage Amlde R C NH2 0 O O J II II II J R C NHR C N amido group R C acyl group 0 II R C NRz Imine Schiff base RNH or R H 2 gtC N or gtC lt imino group R NR or R NH R Disul de R S S R S S disul de linkage i ii Phosphateester R O P O P O phosphoryl group OH OH ii i i i J Diphosphate ester R O li O F 039 Fl 0 l 039 phosphoanhydride group J 0 OH 0 0H i n Phosphatediesterquot R O P O R O F O phosphodiester linkage 039 0 39 quot quot r the groups may be the same or different 39 39 4 hence bear a positive or negative charge bUnuer 39 4 39 AL lf attached to an atom other than carbon o 2008 John Wiley amp Sons Inc All rights reserv Organic FunctionaliGroups you must know these They will show up time and time again in Biochemistry Note that the charge state of some of the groups above will differ in different environmentsconditions eg COOH and COO NH3 and NH4 12 Chemical Evolution 0 n quotk R C OH HN R Condensation Hydrolysis H20 H20 i R C NH R Figure 18 Fundamentals of Biochemistry le 2006 John Wiley amp Sons Many enzymes catalyze hydrolysis and condensation reactions In prebiotic times clay may have provided the environment for catalytic reactions zeolites are used as chemical catalytic environments today In particular the condensation reaction has been very useful throughout evolution for increasing biological complexity Of course the hydrolysis carries out the reverse reaction leading to a loss in H biological complexity Chemical Evolution 2 aaaaaaaaaaaaa m Combination of different functional groups into a large molecule increases its versatility Principle of emergent properties Chemical Evolution Complementarity allows for self replication through templating e g COO NH4 Base complementarity in DNA 2008 John Wiley amp Sons Inc All rights reserved Under these circumstances replication of randomly generated molecules favored evolution A greater advantage was obtained by sequestering and protecting the system With boundaries 5 Cellular Achitecture 7 Proteins him V h d Ribosome Llpopolysacc an e mRNA tRNA DNA Phospholipid RVLipoprotein Peptidoglycan ii Aftera drawing by David Goodsell UCLA Compartmentation Vesicles uid lled sacs are thought to be the precursors to cells These entities would have had the ability to shield selfreplicating chemical reactions and catalyzed reactions so that they were taking place in a sheltered environment giving them a competitive advantage 16 Cellular Achiteoture 7 Proteins him V h d Ribosome Llpopolysacc an e mRNA tRNA DNA Phospholipid f a Lipoprotein Peptidoglycan ii Aftera drawing by David Goodsell UCLA This compartment then has the opportunity to further evolve in order to enhance its advantage A typical animal cell contains as many as 100000 different types of molecules A common bacterium E coli contains millions of molecules representing 30006000 different compounds 17 Prokaryotes and Eukaryotes All modern organisms are based on the same morphological unit the cell Prokaryotes lack a nucleus eg bacteria archaea Eukaryotes membrane enclosed nucleus encapsulating their DNA animals plants fungi Viruses are not cells and are not livinirsince they lack the apparatus to reproduce outside of their host cells Prokaryotes range in size from 1 to 10 MM Eukaryotes range in size from 10 to 100 MM and thus have a thousand to a million times as much volume as a prokaryotic cell 13 Prokagyotic cell Spirillum A spirochete Anabaena a cyanobacterium Esc richia coli Large Bacillus he 0 Staphylococcus If Three species of u Rickettsia Mycoplasma 39 1 0 W Figure 17 Fundamentals of Biochemistry 22 19 2006 John Wiley amp Sons Euka otic Cell Nuclear membrane Endoplasmic reticulum r membrane Rou endoplasmic reticulum Smooth endoplas reticulum Nucleus Nucleolus Endoplasmic reticulum w Cell wall Taxonomy biological class ication Eumya Animals Archaea Fungi Bacteria Sllme molds Plants Halophiles CIIIates Flagellates Grampositives Purple bacteria Methanococcus Microsporid iae Thermoproteus Cyanobacteria Flavobacteria P l 0 g Elma JOhquot Wiley 839 5 quot539 c A rights reserved evolutionary history 22 How do organisms evolve 1 Evolution is not directed toward a particular goal It proceeds via random changes Organisms that are better suited to their environment persevere and ourish 2 Evolution requires some built in variability This is the source of the random changes It allows for adjustment to unexpected changes in the environment 3 Evolution is controlled by its past The new structures and advantages arise from the old 4 Evolution is ongoing Not always toward increasing complexity Physical Units of Space LENGTH You must know this and be comfortable using them Length is very important oc c bond is 154 A Hemoglobin 65A Ribosomes 300A Viruses 100 1000A Prokaryotic cells 1 10 pm or 1 10 X 104 A 10000 100000 A Eulltaryotic cells 10 100 pm or 10 100 X 104 A 100000 1000000 A 1A 10A 100A 1000A 104A 105A 1 gm 10399 lnm 10398m 10397m 10396m 10395m Limit of a light microscope 2000 A or 02 pm 1 A gt 104 A knowledge comes from Xray crystallography electron microscope or atomic force microscope 24 Physical Units of Time Substrates gt Products 10393 sec milli sec ms Unwinding of DNA 10396 sec micro sec us it A 5 1039125 lO399s lO398s 10396s 10393 s lOs femto pico nano micro milli sec r femto fs excitation of chlorophyll pico ps charge separation in photosynthesis nano ns hinge protein action lt 3910398 10 ns uorescence lifetime micro us DNA unwind milli ms enzymatic reactions 39103 5 generation of bacteria K 3923 X 109 5 average human life span Physical Units of Energy Ultimate source of energy is the SUN E hv 57 kcalmol of photons green light or 238000 kJmol air 1 kcal 4184 kJoules 0239 kcal l k You must know how to convert between the two We will be using kJ mol ATP energy carrier for hydrolysis to ADP Pi 7 3 kcalmol or 305 kJmol While Vibrational energy infrared 06 kcalmol or 25 kJmol C C bond 83 kcalmol or 348 kJmol the framework of a carbon skeleton is thermally stable but noncovalent bonds are only a few kcalmol 26 Thermodynamics First Law The First Law of Thermodynamics gt Energy U is conserved it can be neither created nor destroyed AU U nal U q w Most biological processes take place under constant pressure P and variable volume V initial The Enthalpy H of a process is de ned as follows gt H U PV gt AH AU PAV under constant pressure the volume will change like the expansion of a gas The volume changes in biological processes are practically negligible so gt AH z AU 27 Thermodynamics Second Law The Second Law of Thermodynamics Spontaneous processes are characterized by the conversion of order to disorder A process is spontaneous if it can occur without the input of additional energy from the outside ofthe system J Entropy S is the measure ofthe degree of disorder in a system In the system to the right the first system has higher order than the second The second is more disordered The entropy increases on going from the first to the second system The entropy randomness is calculated by S KB ln W KB Boltzmann constant W eq ways Thermodynamics Second Law The spontaneity of a process cannot be predicted from a knowledge of the change in entropy alone 2 H2 029 2 H20 What is the criterion for a spontaneous process At constant temperature and pressure AS ZAHT or AH TAS S O Gibbs Free Energy G The Free Energy GJ change of a spontaneous process is negative Free energy is de ned as followszG H TS Normally we are interested in the change in free energy so the following equation is more useful AG AH TAS For a spontaneous process AG lt 0 If the AG is lt O the process is called exergonic If the AG is gt O the process is called endergonic If the AG is 0 the process is called equilibrium 3O Variation of Reaction Spontaneity Sign of AG with the Signs of AH and AS AG AH TAS The reaction is both enthalpically favored exothermic and entropically favored It is spontaneous exergonic at all temperatures The reaction is enthalpically favored but entropically opposed It is spontaneous only at temperatures below T AH IAS The reaction is enthalpically opposed endothermic but entropically favored It is spontaneous only at temperatures above T AH IAS The reaction is both enthalpicallyand entropically opposed It is nonspontaneousendergonic at all temperatures 2008 John Wiley 8 Sons Inc All rights reserved Equilibrium Constants Relationships between concentration and free energy AGO RT In Keq where AGO is the free energy change in the standard state R is the gas constant 83145 JKmol aAbBeCCdD C lchld AlalBlb At equilibrium AGO so AGO RTln Keq AG AGO RT1n q AZqBZq Standard state conventions in biochemistry The activity of pure water is assigned a value of 1 even though it concentration is really 555 M M Molar Therefore the terms for the concentration of water H20 in equilibrium expressions can be ignored The standard pH is 70 10397 M 0 Temperature is 25 C Pressure is 1 atm atmosphere Standard concentration is 1M Life obeys the laws of thermodynamics Radiant energy from the sun Heat loss 2008 John Wiley 8 Sons ln All rights reserved Living organisms are open systems at steady state Each step of a biochemical process is not required to be exergonic As long as the overall pathway is exergonic it will operate in a forward manner Thus the free energy of ATP hydrolysis a highly exergonic reaction is harnessed to drive many otherwise endergonic biological processes to completion 35 For next time Work assigned Chapter 1 problems Book 1 5 14 Companion 14 16a 16C 0 We will work some ofthem next time in class Read Chapter 2 We will cover most of it next time in class