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29 June, 21:53

Citrate, the product of reaction 1 of the citric acid cycle, inhibits phosphofructokinase, which catalyzes the third reaction of glycolysis. Based on the importance of metabolic flux and the body meeting its metabolite needs, why is this important when there is an excessive buildup of citrate?

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  1. 29 June, 22:09
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    Excessive buildup of citrate informs the body that it need not break down or degrade glucose any longer for the synthesis of biosynthetic precursor molecules needed for the synthesis of fatty acids as there are enough building blocks of this molecules in circulation.

    Explanation:

    The regulatory control of glycolysis are mostly found in the irreversible enzyme catalying reactions of glucolysis. The reactions catalyzed by hexokinase, phosphofructokinase and private kinase are potential sites of control. Glycolysis provides for the production of ATP through glucose degradation and also building blocks for biosynthetic processes such as the synthesis of fatty acids, the availablility of these materials should therefore inhibit the action of glycolysis. High level of ATP inhibits the enzyme phoshofructokinase in the liver and hence decrease it's affinity for fructose 6 phosphate.

    In addition to that, the accumulation of citrate, an intermediate in citric acid cycle inhibits this enzyme phosphofructokinase and hence stop the process of production of biosynthetic precursors since these precursors are already in abundance. Citrate performs this inhibitory effect by enhancing the inhibitory effect of excess ATP on phosphofructokinase.

    So therefore, body meets it's ATP needs and biosynthetic precursor needs and once that is done, it signals for a halt in the further production of this molecules until the substances are depleted.
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