1 / 29

SOME CHEMICAL PRINCIPLES TO BE COVERED

FOR THE FOLLOWING 10 REACTIONS WHICH YOU HAVE ALREADY SEEN THUS FAR IN YOUR STUDY OF BIOCHEMISTRY, INDICATE THE ENZYME BY NAME OR BY CLASS ...

RoyLauris
Download Presentation

SOME CHEMICAL PRINCIPLES TO BE COVERED

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


    MOLECULAR BIOCHEMISTRY II INTRODUCTORY LECTURE SYLLABUS AMINO ACID BIOSYNTHESIS ENERGY METABOLISM OBESITY DIABETES ATKINS DIET NUCLEOTIDE METABOLISM DNA STRUCTURE DNA – PROTEIN INTERACTIONS TRANSCRIPTION FACTORS DNA METHYLATION PHOTOSYNTHESIS

    Slide 2:SOME CHEMICAL PRINCIPLES TO BE COVERED

    BIOCHEMICAL PATHWAYS ENZYME CLASSIFICATION MECHANISMS REGULATORY CONTROL ROLE OF METAL IONS IN BIOCHEMISTRY PRINCIPLES OF CATALYSIS TRANSITION STATES COFACTORS ADDITION OF C1 UNITS OXIDATION/REDUCTION REACTIONS

    Slide 3:ENZYME CLASSIFICATION

    SIX CLASSES ( http://us.expasy.org/enzyme/ ) NOMENCLATURE COMMITTEE OF INTERNATIONAL UNION OF BIOCHEMISTRY AND MOLECULAR BIOLOGY (1992) COVALENT CHEMICAL BONDS MADE/BROKEN OXIDOREDUCTASES TRANSFERASES HYDROLASES LYASES ISOMERASES LIGASES ADDITIONAL CLASS (“ENERGASES”) PHYSICAL REACTIONS NON-COVALENT PRODUCT-LIKE AND SUBSTRATE-LIKE STATES

    Slide 4:WHAT CONSTITUTES A CHEMICAL BOND?

    “…there is a chemical bond between two atoms or groups of atoms in case that the forces acting between them are such as to lead to the formation of an aggregate with sufficient stability to make it convenient for the chemist to consider it as an independent molecular species.” Linus Pauling in “The Nature of the Chemical Bond”

    Slide 5:SIX TRADITIONAL ENZYME CLASSES

    CAN YOU RECOGNIZE THE CLASS TO WHICH AN ENZYME BELONGS BY LOOKING AT THE OVERALL REACTION? IN-CLASS EXERCISE FOR THE FOLLOWING 10 REACTIONS WHICH YOU HAVE ALREADY SEEN THUS FAR IN YOUR STUDY OF BIOCHEMISTRY, INDICATE THE ENZYME BY NAME OR BY CLASS

    Slide 6: SIX ENZYME CLASSES

    OXIDOREDUCTASE TRANSFERASE HYDROLASE LYASE ISOMERASE LIGASE

    Slide 7:CATALYSIS OF “PHYSICAL” REACTIONS

    PRODUCT-LIKE AND SUBSTRATE-LIKE STATES: EXAMPLES : CHAPERONIN-MEDIATED (PROTEIN FOLDING) CHROMATIN CONDENSATION “MOLECULAR MOTOR” OPERATION DNA PROCESSING BY POLYMERASES ACTIVE AND CARRIER-MEDIATED TRANSPORT G-PROTEIN MEDIATED REGULATION OF HORMONE RECEPTORS MEMBRANE TRANSPORTERS (PUMPS) ARE NOW RECOGNIZED AS A SPECIAL CLASS OF ENZYMES “ENERGASES” : TRANSDUCE ENERGY FROM COVALENT BONDS INTO MECHANICAL WORK

    Slide 8:“ENERGASES”

    MEDIATE NUCLEOSIDE TRIPHOSPHATE HYDROLYSIS THE FREE ENERGY RELEASED IS COUPLED TO SYSTEM’S CONFORMATIONAL CHANGE ARE ATPases AND GTPases CORRECTLY CLASSIFIED AS “HYDROLASES”? ATP + H2O ? ADP + Pi + HEAT Keq = [ADP][Pi] / [ATP] ?Ghydrolysis IS RELEASED AS HEAT HERE THE ENZYME IS ATPase AND IT’S A HYDROLASE

    Slide 9:ENERGASE EXAMPLE

    A SYNTHETASE REACTION: ATP + GLU + NH3 ? GLN + ADP + Pi HERE THE ?Ghydrolysis IS COUPLED TO ?Gsynthesis THROUGH A REACTIVE INTERMEDIATE Keq = [GLN][ADP][Pi] / [ATP][GLU][NH3] = [GLN] / [GLU][NH3] X [ADP][Pi] / [ATP] AN ENERGASE REACTION: ATP + STATE 1 + H2O ? ADP + STATE 2 + Pi HERE THE ?Ghydrolysis IS COUPLED TO ?Gconformational change Keq = [STATE 1] / [STATE 2] X [ADP][Pi] / [ATP] NOTICE SIMILARITY TO Keq FOR SYNTHETASE REACTION THERE’S NO CHEMICAL (COVALENT) CHANGE, THOUGH

    Slide 10:ENZYMES AS MECHANOCHEMICAL PROTEINS

    THE GIBBS FREE ENERGY OF ATP HYDROLYSIS IS TRANSDUCED INTO A FORM OF USEFUL WORK TRANSLATION ROTATION SOLUTE GRADIENT A RECIPROCAL RELATIONSHIP ENZYMES USE NON-COVALENT INTERACTIONS TO BREAK COVALENT BONDS ENERGY FROM BREAKING COVALENT BONDS CAN MODIFY NON-COVALENT INTERACTIONS

    KEY CONCEPTS IN ORGANIC CHEMISTRY THE “SIX PILLARS” ELECTRONEGATIVITY POLAR COVALENT BONDING STERIC EFFECTS INDUCTIVE EFFECTS RESONANCE AROMATICITY Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 ELECTRONEGATIVITY Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 POLAR COVALENT BONDING Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 STERIC EFFECTS Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 INDUCTIVE EFFECTS Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 RESONANCE Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 AROMATICITY Mullins, J.J. “Six pillars of organic chemistry”, J. Chem. Educ. 2008, 85(1), 83-87 SUGGESTION FOR LEARNING BIOCHEMICAL MECHANISMS WHENEVER POSSIBLE, TRY TO RATIONALIZE MECHANISMS USING ONE OR MORE OF THESE “PILLARS”

    Slide 19:AN INTRODUCTION TO AMINO ACID METABOLISM

    NITROGEN CYCLE THE “FIXTATION” OF NITROGEN THE CENTRAL ROLE OF GLUTAMATE

    Slide 20:THE NITROGEN CYCLE

    N2 IS A VERY STABLE MOLECULE BOND ENERGY = 941.4 kJ/MOL COMPARED TO 498.7 kJ/MOL FOR O2 A SINGLE C=O BOND IN CO2 IS 799 kJ/MOL HOW IS IT METABOLIZED (“FIXED”)? THE “NITROGEN CYCLE” PRODUCTION OF METABOLICALLY USEFUL NITROGEN NITRITES NITRATES AMMONIA

    Slide 21:THE NITROGEN CYCLE

    N-FIXING ORGANISMS: ANAEROBES MARINE CYANOBACTERIA “DIAZOTROPHS” DIAZOTROPHS COLONIZE ROOT NODULES OF LEGUMES GENUS Rhizobium SYMBIOTIC RELATIONSHIP ENZYME IS “NITROGENASE” THE NITROGENASE REACTION: N2 + 8 H+ + 8 e- + 16 ATP + 16 H2O ? 2 NH3 + H2 + 16 ADP + 16 Pi REQUIRES ATP AND ELECTRONS CONTAINS Fe AND Mo

    Slide 22:THE NITROGEN CYCLE

    ENERGETICALLY COSTLY NEED 16 ATPs TO “FIX” ONE N2 MOLECULE COMPARE THIS TO INDUSTRIAL FIXATION: TEMPERATURE 300o - 500o C PRESSURE > 300 ATM METAL CATALYST NH3 FORMED IS USED IN FORMATION OF GLUTAMATE (Glu Dehydrogenase) GLUTAMINE (Gln Synthetase) EXCESS NH3 EXCRETED INTO SOIL RESTORE USABLE NITROGEN BY PLANTING ALFALFA

    Slide 23:THE NITROGEN CYCLE

    MOST PLANTS DO NOT SUPPORT N-FIXING BACTERIA NEED PRE-FIXED NITROGEN SOURCE NH3 NO2- NO3- SOURCES: LIGHTNING (10% OF NATURALLY-FIXED N) FERTILIZERS DECAY OF ORGANIC MATTER IN SOIL

    Slide 24:THE NITROGEN CYCLE

    PLANTS, FUNGI, BACTERIA REDUCE NO3-: A TWO-STEP PROCESS NO3- + 2H+ + 2e- ? NO2- + H2O ENZYME: NITRATE REDUCTASE NO2- + 8H+ + 6e- ? NH4+ + 2H2O ENZYME: NITRITE REDUCTASE SOME BACTERIA CAN OXIDIZE NH4+ “NITRIFICATION” NH4+ ? NO2- AND THEN TO NO3- DENITRIFICATION CONVERSION OF NO3- TO N2 BY OTHER BACTERIA

    Slide 25:THE NITROGEN CYCLE

    ATMOSPHERIC N2 IS THE ULTIMATE NITROGEN SOURCE N2 NH4+ NO3- NO2- NITROGEN FIXATION NITRIFICATION DENITRIFICATION NITROGENASE NITRATE REDUCTASE NITRITE REDUCTASE

    Slide 26:ORGANISMS ASSIMILATE NH3

    ROLE OF GLUTAMINE SYNTHETASE MICRO-ORGANISMS: ENTRY POINT FOR FIXED N GLU + ATP + NH4+ ? GLN + ADP + Pi IN ALL ORGANISMS, GLN IS AN AMINO GROUP CARRIER GLUTAMATE SYNTHASE IN BACTERIA, PLANTS ?-KETOGLUTARATE + GLN + NADPH + H+ ? 2 GLU + NADP+ OVERALL RXN’: ?-KG + NH4+ + ATP + NADPH + H+ ? GLU + NADP+ + ADP + Pi

    Slide 27:THE CENTRAL ROLE OF GLUTAMATE

    “GLUTAMATE FAMILY” OF AMINO ACIDS DEGRADATIVE METABOLISM CONVERGES ON THAT OF GLU GLU GLN PRO HIS ARG ORNITHINE GLU IS THE PRECURSOR OF PRO ORNITHINE ARG GLU/?-KG ARE TRANSAMINATION PARTNERS AMINO ACID + ?-KG ? GLU + ?-KETOACID OXIDATIVE DEAMINATION OF GLU (GLU DEHYDROGENASE) GLU + NAD(P)+ + H2O ? ?-KG + NAD(P)H + NH4+ N-ACETYLGLUTAMATE SYNTHESIS ALLOSTERICALLY REGULATES CPS I OF UREA CYCLE GLU + ACETYL-CoA ? N-ACETYL GLUTAMATE

    Kelly A., Stanley CA. (2001). “Disorders of Glutamate Metabolism”. Mental Retard- Ation and Developmental Disorders. 7:287-295.

    Slide 29:CLOSING POINTS

    HIGH ENERGY COSTS TO FIX NITROGEN ITS USE MUST BE CAREFULLY CONTROLLED GLU AND GLN ARE PIVOTAL IN AMINO GROUP TRANSFER GLU OFTEN DONATES THE AMINO GROUP GLN STORES, CARRIES AMINO GROUPS TRANSAMINASES CATALYSTS FOR TRANSFER OF AMINO GROUPS TO a-KETOACIDS FREELY REVERSIBLE REACTIONS ? IMPORTANT IN BOTH SYNTHETIC AND DEGRADATIVE PATHWAYS

More Related