Hypotheses on the Physiological Role of Enzymatic Protein Methyl Esterification Using Human Erythrocytes as a Model System

  • Patrizia Galletti
  • Caterina Manna
  • Diego Ingrosso
  • Patrizia Iardino
  • Vincenzo Zappia
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 307)


Among the different theories of aging, the “error catastrophe” hypothesis, first postulated by Orgel in 1963 (1), attracted the interest of scientists by proposing that errors in protein biosynthesis might accumulate with age and reach a catastrophic level at which several vital components of an organism could no longer function to sustain life. Despite the overwhelming evidence against this theory, an important prediction of Orgel’s hypothesis was that abnormal proteins would accumulate during cell aging. As a matter of fact, abnormal forms of several proteins were found in aged tissues (2); however, they do not arise from errors in protein biosynthesis, as originally predicted, but as a consequence of several spontaneous modifications which occur post-translationally. There are, indeed, a number of time-dependent spontaneous reactions (3), i.e. deamidation, racemization, glycation and oxidation, that may alter the covalent structure of proteins, which occur at such rates that significant damage to long-lived proteins accumulates during the life time of the cells. In this respect, it is conceivable that systems have evolved to avoid the accumulation of aberrant proteins, either by their selective proteolysis or through the action of protective enzymes, and a failure of both these systems could be one of the mechanisms responsible for the cell aging. The protective enzymes should be particularly efficient in those cells where an impairment or a loss of protein biosynthesis had occurred, thus preventing the protein turnover. Therefore human erythrocytes represent an excellent model system to study either the relationship between post-translational chemical modifications of proteins and cell aging, or the presence of enzymatic systems that deal with this time-dependent protein damage.


Human Erythrocyte Methyl Esterification Triose Phosphate Isomerase Isopeptide Bond Cyclic Imide 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Patrizia Galletti
    • 1
  • Caterina Manna
    • 1
  • Diego Ingrosso
    • 1
  • Patrizia Iardino
    • 1
  • Vincenzo Zappia
    • 1
  1. 1.Department of Biochemistry of Macromolecules1st Medical School, University of NapoliItaly

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