MOLECULAR%20BIOCHEMISTRY%20II%20INTRODUCTORY%20LECTURE - PowerPoint PPT Presentation

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MOLECULAR%20BIOCHEMISTRY%20II%20INTRODUCTORY%20LECTURE

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... GLU NH3 GLN ADP Pi. HERE THE Ghydrolysis IS COUPLED ... ADP STATE 2 Pi ... 16 ATP 16 H2O 2 NH3 H2 16 ADP 16 Pi. REQUIRES ATP AND ELECTRONS ... – PowerPoint PPT presentation

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Title: MOLECULAR%20BIOCHEMISTRY%20II%20INTRODUCTORY%20LECTURE


1
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

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

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

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

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

6
SIX ENZYME CLASSES
  • OXIDOREDUCTASE
  • TRANSFERASE
  • HYDROLASE
  • LYASE
  • ISOMERASE
  • LIGASE

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

8
ENERGASES
  • MEDIATE NUCLEOSIDE TRIPHOSPHATE HYDROLYSIS
  • THE FREE ENERGY RELEASED IS COUPLED TO SYSTEMS
    CONFORMATIONAL CHANGE
  • ARE ATPases AND GTPases CORRECTLY CLASSIFIED AS
    HYDROLASES?
  • ATP H2O ? ADP Pi HEAT
  • Keq ADPPi / ATP
  • ?Ghydrolysis IS RELEASED AS HEAT
  • HERE THE ENZYME IS ATPase AND ITS A HYDROLASE

9
ENERGASE EXAMPLE
  • A SYNTHETASE REACTION
  • ATP GLU NH3 ? GLN ADP Pi
  • HERE THE ?Ghydrolysis IS COUPLED TO ?Gsynthesis
  • THROUGH A REACTIVE INTERMEDIATE
  • Keq GLNADPPi / ATPGLUNH3
  • GLN / GLUNH3 X ADPPi / 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 ADPPi / ATP
  • NOTICE SIMILARITY TO Keq FOR SYNTHETASE REACTION
  • THERES NO CHEMICAL (COVALENT) CHANGE, THOUGH

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

11
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

12
ELECTRONEGATIVITY
Mullins, J.J. Six pillars of organic chemistry,
J. Chem. Educ. 2008, 85(1), 83-87
13
POLAR COVALENT BONDING
Mullins, J.J. Six pillars of organic chemistry,
J. Chem. Educ. 2008, 85(1), 83-87
14
STERIC EFFECTS
Mullins, J.J. Six pillars of organic chemistry,
J. Chem. Educ. 2008, 85(1), 83-87
15
INDUCTIVE EFFECTS
Mullins, J.J. Six pillars of organic chemistry,
J. Chem. Educ. 2008, 85(1), 83-87
16
RESONANCE
Mullins, J.J. Six pillars of organic chemistry,
J. Chem. Educ. 2008, 85(1), 83-87
17
AROMATICITY
Mullins, J.J. Six pillars of organic chemistry,
J. Chem. Educ. 2008, 85(1), 83-87
18
SUGGESTION FOR LEARNING BIOCHEMICAL MECHANISMS
  • WHENEVER POSSIBLE, TRY TO RATIONALIZE MECHANISMS
    USING ONE OR MORE OF THESE PILLARS

19
AN INTRODUCTION TO AMINO ACID METABOLISM
  • NITROGEN CYCLE
  • THE FIXTATION OF NITROGEN
  • THE CENTRAL ROLE OF GLUTAMATE

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 CO BOND IN CO2 IS 799 kJ/MOL
  • HOW IS IT METABOLIZED (FIXED)?
  • THE NITROGEN CYCLE
  • PRODUCTION OF METABOLICALLY USEFUL NITROGEN
  • NITRITES
  • NITRATES
  • AMMONIA

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

22
THE NITROGEN CYCLE
  • ENERGETICALLY COSTLY
  • NEED 16 ATPs TO FIX ONE N2 MOLECULE
  • COMPARE THIS TO INDUSTRIAL FIXATION
  • TEMPERATURE 300o - 500o C
  • PRESSURE gt 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

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

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

25
THE NITROGEN CYCLE
  • ATMOSPHERIC N2 IS THE ULTIMATE NITROGEN SOURCE

N2
DENITRIFICATION
NO3-
NITRATE REDUCTASE
NITROGENASE
NITROGEN FIXATION
NO2-
NITRITE REDUCTASE
NITRIFICATION
NH4
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

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

28
Kelly A., Stanley CA. (2001). Disorders of
Glutamate Metabolism. Mental Retard- Ation and
Developmental Disorders. 7287-295.
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
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