For over 200 million years, milk has co-evolved with mammalian infants to be nourishing and immunoprotective. Scientists are now realizing that milk is not simply a mixture of basic nutritional building blocks, but rather a dynamic, active and personal source of nourishment to the human infant. Fragments of milk proteins released during infant digestion have an array of biological functions within the gut and systemically. These peptides are typically inactive within the sequence of the parent protein and only become active when released by proteolysis.
For the majority of mammalian evolution, milk evolved with term-delivered infants as the digestive partner because historically most premature infants (infants born at <37 weeks of gestation in humans) did not survive. Only through modern medical interventions do the majority of premature infants now survive to adulthood. Thus, premature infants have had no influence on the evolution of human milk. In essence, bioactive peptide fragments evolved to be released in the digestive milieu of the term infant.
Premature infants have a reduced capacity for protein digestion in comparison with term infants. A reduced proteolytic capacity means that biologically active milk protein fragments released by the specific digestive milieu of the term infant will not be released in the preterm infant. Therefore, the premature infant will not obtain the benefit of the peptide fragments' biological functions, which could be partially responsible for the increased risks of morbidity found in preterm infants compared to term infants.
The foundation of this research is a detailed characterization of the peptide and glycan components of human milk as outlined in chapters 1 and 2. The peptides and glycans were identified with automated nano-liquid chromatography quadrupole time-of-flight tandem mass spectrometry and de novo peptide sequencing. Bioinformatic techniques were used to compare the found peptide sequences to functional domain databases to determine hypothetical peptide function.
The overarching goals of this research are to discover novel bioactive peptides and improve premature infant feeding solutions.
|Advisor:||German, John Bruce|
|Commitee:||Lebrilla, Carlito B., Underwood, Mark A.|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||DAI-B 74/02(E), Dissertation Abstracts International|
|Subjects:||Food Science, Nutrition|
|Keywords:||Glycan, Glycopeptidomics, Human milk, Infants, Peptidomics, Premature infant feeding|
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