Lecture #31: Amino Acid Metabolism and the Urea Cycle

Read: pg. 615-625; 640-641; 645; with focus on pages identified in objectives below. Optional Reading: pg 656-658

HW: pg. 661 (Study Exercise 3, 4, 5); pg 662 (2,3,6) - see back of book for answers

Study Exercises:

  1. Summarize the steps of the Urea Cycle: Note that the urea cycle is a cycle. Each turn of the cycle regenerates ornithine. To begin, a carbamoyl group is transferred from carbamoyl phosphate to generate citrulline. This pattern is similar to the TCA cycle where each turn of the cycle regenerates oxaloacetate, and acetate is transferred from acetyl CoA to oxaloacetate to form citrate.

Overall urea cycle reaction is:

NH3 + HCO3- + aspartate + 3 ATP ® urea + fumarate + 2ADP + 2Pi + AMP + PPi (pg.620)

Description of Individual Steps

Enzyme

Cellular Compartment
  1. First N is acquired via condensation and activation of NH4+ and HCO3- to form carbamoyl phosphate

Carbamoyl Phosphate Synthase I (CPS I)

Mitochondrion
  • Transfers cabamoyl group to ornithine to make citrulline
    		•

    Ornithine Transcarbamoylase

    Mitochondrion

    (ornithine is transported into the mito; citrulline is transported out; transport is driven by electrochemical gradient)
  • Second N is acquired via condensation of citrulline's uredio (urea containing) group and aspartate amino group to form argininosuccinate.

    • Note: Urea is now assembled!

    Arginosuccinate synthetase

    Cytosol
  • Fumarate is eliminated leaving arginine.
    		•

    Argininosuccinase

    Cytosol

    Note: the fumarate that is produced is converted back to aspartate. The first two reactions are the same as in the TCA cycle, BUT they occur in the cytosol!
  • Hydrolysis of arginine to yield UREA and regenerate ornithine.

    • Arginase

    Cytosol
    1. Describe the two general metabolic fates of the carbon skeleton of amino acids:
    1. metabolized to CO2 and H2O
    2. used to make glucose and/or ketone bodies (figs 20-5 and 20-11)
    1. What are the metabolic precursors of the nonessential amino acids?

    Pyruvate, oxaloacetate, alpha-ketoglutarate and 3-phosphoglycerate (pg 640, 645)