Peptides as inhibitors of lipoxygenase and tyrosinase

M. Minderhout-Schurink

Research output: Thesisinternal PhD, WU


Oxidation reactions catalyzed by enzymes such as lipoxygenase (LOX) and tyrosinase (TYR) initiate food quality decay. Besides their physiological role in the human body, LOX and TYR are involved in certain types of cancer, neurodegenerative diseases and processes of aging. Most common antioxidants able to retard these oxidations, function by scavenging free radicals or by reducing oxidation products formed by these enzymes. The enzyme activity, which is the cause of the formation of these oxidized compounds, remains unaffected. In addition, most of the conventional oxidative enzyme inhibitors are synthetic, unstable, difficult to obtain and cannot be used in food products, cosmetics or medicines from viewpoints of safety and economics. Hydrolyzed proteins from animal and plant sources have been found to possess antioxidant activity. They have a potential to be used as alternative, natural antioxidants. In the research described in this thesis a novel approach was chosen in order to identify protein-based inhibitors for soybean LOX and mushroom TYR. SPOT synthesis was used to synthesize cellulose-bound peptide libraries containing overlapping peptides derived from proteins originating from different industrial sources such as milk, egg, soy, or wheat. Screening of these libraries with a fluorescent labeled LOX or TYR resulted in a set of peptides that specifically bind to these enzymes. The presence of positively charged residues within the peptide sequence appears to be important for interaction with LOX. Preparative synthesis of some binding peptides and subsequent inhibition assays confirmed a true, noncompetitive inhibition of LOX by the octapeptide RINKKIEK from the milk protein b‑casein. A substitutional analysis showed that replacement of the glutamic acid residue in RINKKIEK significantly improves binding and inhibition of LOX. The molecular determinants for TYR-inhibiting peptides are different from LOX-inhibiting peptides. Strong TYR-binding peptides always contain one or more arginine residues, often in combination with phenylalanine. Furthermore, the presence of valine, alanine and/or leucine contributes to TYR inhibition. An example of a good TYR-binding and -inhibiting peptide is LFRVASMA from egg ovalbumin, which comprises a combination of these amino acid residues. In conclusion, several inhibitory peptides were identified with potencies comparable to nonpeptidic inhibitors. However, further experiments are required in order to assess the applicability of these antioxidant peptides.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • de Vries, Sacco, Promotor
  • van Berkel, Willem, Co-promotor
  • Boeriu, Carmen, Co-promotor
Award date3 Dec 2007
Place of Publication[S.l.]
Print ISBNs9789085048459
Publication statusPublished - 2007


  • lipoxygenase
  • tyrosine 3-monooxygenase
  • enzyme inhibitors
  • peptides
  • food quality
  • oxidation


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