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    BioPatel is offline Member
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    Serum analysis reveals elevated levels of lactate, alanine

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    A 3-month-old child is evaluated for seizures, hypotonia, psychomotor retardation, and poor head control. Serum analysis reveals elevated levels of lactate, alanine, pyruvate, and ketoacids. Based on the clinical presentation, pyruvate carboxylase activity is measured using extracts of cultured skin fibroblasts, and is found to be markedly decreased. This enzyme is normally used to directly synthesize which of the following molecules?

    A. Acetyl CoA
    B. Alpha-ketoglutarate
    C. Citrate
    D. Malate
    E. Oxaloacetate

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    Asclepius1 is offline Ultimate Member 537 points
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    Re: Serum analysis reveals elevated levels of lactate, alanine

    Quote Originally Posted by BioPatel
    A 3-month-old child is evaluated for seizures, hypotonia, psychomotor retardation, and poor head control. Serum analysis reveals elevated levels of lactate, alanine, pyruvate, and ketoacids. Based on the clinical presentation, pyruvate carboxylase activity is measured using extracts of cultured skin fibroblasts, and is found to be markedly decreased. This enzyme is normally used to directly synthesize which of the following molecules?

    A. Acetyl CoA
    B. Alpha-ketoglutarate
    C. Citrate
    D. Malate
    E. Oxaloacetate
    E

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    A.

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    BioPatel is offline Member
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    The correct answer is E. Pyruvate carboxylase is a mitochondrial enzyme that normally catalyzes the reaction:
    Pyruvate + CO2 + ATP → Oxaloacetate + ADP + Pi

    This reaction serves to make the oxaloacetate that is used within the citric acid cycle. A deficiency of this enzyme has very broad metabolic consequences because the citric acid cycle is downregulated, with resultant downregulation of the energy-producing capacity of the cell. In addition to a general loss of energy in the cell, pyruvate levels rise because pyruvate is not reprocessed into oxaloacetate, alanine levels rise because the normal conversion to pyruvate is feedback-inhibited, and ketoacids rise because anaerobic metabolism is stimulated. Clinically, pyruvate carboxylase deficiency is a fortunately rare but devastating disease for which we presently have no effective therapy.

    Acetyl CoA (choice A) acts as an activator for pyruvate carboxylase.

    Alpha-ketoglutarate (choice B), citrate (choice C), and malate (choice D) are also citric acid cycle intermediates whose levels drop when pyruvate carboxylase activity is low, but this effect is a secondary one that follows decreased levels of oxaloacetate as the citric acid cycle sequence of reactions occurs.

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