metabolic pathways and feedback mechanisms - 7

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Unformatted text preview: 7-1Cell and Molecular Biology (Biol. Chem. 410A)Lecture #7Harry R. Matthews, Ph.D.October 4, 1996Metabolic Pathways and Feedback MechanismsClinical correlations:cancer chemotherapyfluorouracilmethotrexateLearning objectives:metabolic pathwaysdeoxynucleoside triphosphatescooperativityallosteric effectorsOptional reading:Stryer IV: Chapter 10any inborn errors of metabolism lead to disease due to a loss of a single enzyme activity in the body. In order to understand how this loss affects the body's function and learn how to treat these diseases, we need to see how individual enzymes fit into the overall picture of the body's metabolism. Metabolic pathways show us the oftencomplex effects of drugs acting on specific enzymes and we will discuss two examples, fluorouracil and methotrexate.MMetabolic PathwaysA cell is rarely able to catalyze a desired chemical reaction in one step. There are vari-ous reasons for this, related to issues of en-ergy conservation, control and evolution. For example, the breakdown of glucose (glycolysis) takes place in many steps whose functions in-clude generating the largest possible number of ATP and other energy-rich molecules, giv-ing the cell as much useful energy as possible from each glucose molecule. Thus, reactions occur through a sequence of steps, called a metabolic pathway. These pathways are con-trolled in complex ways in the body and un-derstanding these control mechanisms is cru-cial for intervention in diseases involving metabolic processes or enzymes. Control refers both to the determination of which of the many possible reactions will actually be catalyzed (reaction specificity) and the rate at which the reactions are catalyzed (reaction ve-locity).Reaction specificity is limited by the en-zymes which are available to the cell through being encoded in the genes. Different cells can modify the spectrum of enzymes they use by controlling gene expression. Hence, some en-zymes which are used by all cells (sometimes called housekeeping enzymes) are always available. Other, more specialized, enzymes will only be available in the appropriate cells. While some of these latter enzymes can be synthesized or not in response to cellular needs, many of them are determined by the cell type and do not change much during the life of a fully differentiated cell.However, a cell must respond to changing environments and changing requirements. This response is frequently achieved by chan-ging the rate at which specific reactions are catalyzed, i.e., by changing the activity of spe-cific enzymes. Changes in enzyme activity are actually going on as a continuous process ne-...
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