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    UNIT 1: Introduction - Chemical and PhysicalFoundations of Biochemistry

    Learning goals : to understand about Roles of small and large biomolecules

    Energy transformation in living organisms

    Regulation of metabolism and catalysis

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    Albert Lehninger (1917-1986)Citric acid cycle occurs in mitochondria

    Mechanism of oxidative phosphorylation

    Mitochondrial structure and function

    Bioenergetics

    Author of classic textbooks :

    B iochemistry (1970-1983)The Mitochondrion (1964)

    B ioenergetics (1965 -1974)

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    T he Interface Between Biology and

    Chemistry

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    Chemistry within the Cell

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    Biochemistry : Unique Role of Carbon

    Biomolecules are carbon-basedElements H, O, N, P, S are also commonMetal ions (e.g. K +, Na +, Ca ++, Mg++, Zn++, Fe ++) playimportant roles in metabolismTogether, about 30 elements are essential for life

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    Biological Molecules T ypically HaveSeveral Functional Groups

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    Structure of Biological Molecules isImportant

    T he function of molecules strongly depend on three-dimensional structure

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    Stereoisomers have DifferentBiological Properties

    Cis and trans isomers have also different physical andchemical properties

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    Optical Isomers have Different BiologicalProperties

    Enantiomers have identical physical properties (except regardto polarized light ) and react identically with achiral reagents.

    Diastereomers have distinct chemical and biologicalproperties because bio-molecules are themselves chiral.

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    Interactions between Bio-molecules areSpecific

    Macromolecules have unique binding pockets

    Only certain molecules fit in well and can bind

    Binding of chiral bio-molecules is stereospecific

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    T he Molecular Logic of Life

    We look at the chemistry that is behind :

    Accelerating reactions

    Organization of metabolism and signaling

    Storage and transfer of information

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    How to Speed Reactions Up?

    Higher temperatures

    Stability of macromolecules is limiting

    Higher concentration of reactants

    Costly as more valuable starting material isneeded

    Lower activation barrier by catalysis

    Universally used by living organismsChange the reaction by coupling to a fast one

    Universally used by living organisms

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    Unfavorable and Favorable

    ReactionsSynthesis of complex molecules and many other metabolicreactions requires energy (endergonic )

    A reaction might be thermodynamically unfavorable (( Gr

    > 0)

    Creating order requires work and energy Metabolic reaction might have too high energy barrier (( G > 0)

    Metabolite is kinetically stable

    Breakdown of some metabolites releases significant amount of energy (exergonic )

    Such metabolites (ATP, NADH, NADPH) can be synthesizes using the energyfrom sunlight and fuels

    Their cellular concentration is far higher than their equilibriumconcentration.

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    Catalysis

    A catalyst is a compound that increases the rate of achemical reaction

    Catalysts lower the activation free energy ( G

    Catalysts does not alter ( G

    Catalysis offers : Acceleration under mild conditions High specificity Possibility for regulation

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    Energy Coupling

    Chemical coupling of exergonic and endergonicreactions allows otherwise unfavorable reactions toproceed

    Biology often links the hydrolysis of the high-energymolecule AT P directly with the metabolite that needs

    activation thus coupling the two reactions.

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    AT P: Chemical Currency of Energy

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    Metabolic Pathwayproduces energy or valuable materials

    Signal Transduction Pathwaytransmits information

    Series of Related ReactionsForms a Pathway

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    Example of a negative regulation :Product of enzyme 5 inhibits enzyme 1

    Pa thw ays Are Contr o lled in Order toRegul a te Level s of M et a b o lite s

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    Chapter 1: Summary

    T he main learning goals were :To relate structure and function of the cellTo realize that the structure of biomoleculesoften gives them specific functionsTo grasp principles of bioenergetics