Selective Proteolysis of α-Lactalbumin by Endogenous Enzymes of Human Milk at Acidic pH

Junai Gan, Jingyuan Zheng, Nithya Krishnakumar, Elisha Goonatilleke, Carlito B. Lebrilla, Daniela Barile, J. Bruce German

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Scope: The use of human milk products is increasing for high-risk infants. Human milk contains endogenous enzymes that comprise a dynamic proteolytic system, yet biological properties of these enzymes and their activities in response to variations including pH within infants are unclear. Human milk has a neutral pH around 7, while infant gastric pH varies from 2 to 6 depending on individual conditions. This study is designed to determine the specificity of enzyme–substrate interactions in human milk as a function of pH. Methods and results: Endogenous proteolysis is characterized by incubating freshly expressed human milk at physiologically relevant pH ranging from 2 to 7 without the addition of exogenous enzymes. Results show that the effects of pH on endogenous proteolysis in human milk are protein-specific. Further, specific interactions between cathepsin D and α-lactalbumin are confirmed. The endogenous enzyme cathepsin D in human milk cleaves α-lactalbumin as the milk pH shifts from 7 to 3. Conclusions: This study documents that selective proteolysis activated by pH shift is a mechanism for dynamic interactions between human milk and the infant. Controlled proteolysis can guide the use of human milk products based on individual circumstance.

Original languageEnglish (US)
Article number1900259
JournalMolecular Nutrition and Food Research
StatePublished - Jan 1 2019


  • bioactivity
  • human milk
  • pH
  • protein
  • selective proteolysis

ASJC Scopus subject areas

  • Biotechnology
  • Food Science


Dive into the research topics of 'Selective Proteolysis of α-Lactalbumin by Endogenous Enzymes of Human Milk at Acidic pH'. Together they form a unique fingerprint.

Cite this