1999.3.2
Introduction to Metabolism
(Voet & Voet Chapter 15) 

I. Thermodynamic Backgrounds

    1. Free energy change in biochemical reaction

        £GG = £GG0¡¦ + RT ln Q (Q = [products]/[reactants])

    2. Oxidation-reduction (Redox) reactions

        £GG = - nF£GE (£GE = the electromotive force, emf, or redox potential)

         [Could you resolve the Nernst equation?]

    3. Enzyme effects in biochemical reaction

    4. Bioenergetics

        Phototrophs vs Chemotrophs

        ATP and NADH are the free energy carriers

        Electrochemical gradient (Proton gradient)

            £GG = 2.3 RT [£GpH] + ZF£G£Z

     5. Thermodynamics of life

Living system is in nonequilibrium thermodynamics - steady state (open system), is its state of maximum thermodynamic efficiency.
Thermodynamics of metabolic control are based on enzymes selectivity and enzymes operating far from equilibrium.


II. Metabolic Pathway

Metabolic pathways are sequences of enzyme-catalyzed chemical reactions that bring about transformations of certain organic compounds. Four general types can be differentiated:

1. Catabolic. Primarily degradative processes in which large organic molecules are broken down into simple cellular constituents with release of chemical-free energy. Often oxidative and converts NAD+ to NADH.

2. Anabolic. Synthetic processes in which complex organic materials are made from simple precursors. Often reductive, using NADPH as the source of reducing power.

3. Central or amphibolic. The paradigm is the Krebs cycle¡]also known as TCA or the citric acid cycle¡^- a link between anabolic and catabolic routes; usually provides energy and/or the interconversion of intermediate metabolites that are required for other processes.

4. Anaplerotic. Reactions or small sequences of reactions that replenish pools of intermediates in major pathways.

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 Some General Principles
 
1). Catabolic and anabolic pathways are not simple reversals of one another. For example,glycolysis¡]glucose breakdown¡^and gluconeogenesis¡]glucose synthesis¡^both occur in the liver, but there are enzymatic reactions on each pathway that are not shared with the other one. ¡]Why?¡^
2). Metabolic pathways often have a preparatory phase in which the starting materials are first activated¡]e.g., by phosphorylation at the expense of ATP or by formation of a nucleotide derivative, a thioester with coenzyme A).
3). Regulation of metabolic pathways may be achieved by:
a). Changes in enzyme activity
             (1) Effected by metabolites-activation, inhibition, allosterism
   (2) Activation or inhibition achieved by covalent modification of the enzyme, e.g., by phosphorylation(or adenylation, or ADP-ribosylation) of the enzyme protein itself
b). Changes in the level of the enzyme present in the cell by production of more enzyme (increasing the transcription or translation leading to that enzyme protein)
¡iHow can you tell whether an increase in enzyme activity results from¡]a¡^or¡]b¡^?¡j
c).  Metabolites, and sometimes ions, are regulators that act within a cell. Hormones lead to regulatory effects that allow different cell types to act in a coordinate fashion to serve the needs of the whole organism. Important metabolic steps will generally be controlled both at the level of metabolites and hormones. The hormonal signal usually can override the metabolite signal. Key regulatory steps on metabolic pathways are often irreversible and are often found at the beginning, the end, and at branch points on metabolic pathways.


4). Metabolic pathways in eukaryotic cells occur in specific cellular locations/compartments.

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III. Experimental Approaches to the Study of Metabolism

1. Metabolic inhibitors, growth studies, and biochemical genetics

2. Isotopes
     NMR can be used to study metabolism in whole animals

3. Isolated organs, cells, and subcellular organelles

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Practice Problem : Question 4 of the Chapter 15 (Voet and Voet p. 442)
 

Last modified on 1999.3.21 by K.-J. Hsiao (¿½¼s¤¯)                       [ ­º­¶ ]