AbstractVitamins are a group of biochemically and metabolically diverse essential micronutrients required for health, homeostasis, and development. The majority of vitamins cannot be endogenously synthesised sufficiently to satisfy physiological requirement, and therefore must be dietary sourced. Transit of vitamin metabolites through the circulation is facilitated by a number of transport proteins. Proteomic analyses have indicated three of these transport proteins; vitamin D-binding protein, haptocorrin (vitamin B12-binding protein), and retinol-binding protein (vitamin A-binding protein) are constituents of a number of exocrine secretions, including saliva. The aim of this study was to determine whether salivary vitamin-binding proteins have assimilatory functions in respect to their corresponding vitamin ligands, or if they support oral homeostasis.
The relationships between salivary and serum vitamin-binding protein concentrations with commonly employed circulatory markers of systemic vitamin status were determined to assess their suitability as non-invasive biomarkers of vitamins status. Studies were undertaken to define the origin of vitamin-binding proteins in the oral cavity, which may relate to their function.
Vitamin deficiencies have been reported in the common inflammatory disorder; periodontal disease. In this study, longitudinally paired saliva and serum samples from a periodontal disease cohort were assessed before and after treatment to determine if hypovitaminosis was a consequence of disrupted salivary vitamin-binding protein function. Interactions between haptocorrin, and the periodontal disease-associated pathobiont; Porphyromonas gingivalis, were experimentally considered.
The findings of this thesis indicate the vitamin-binding proteins studied originated from salivary glands and their outputs increased with mastication. Upregulation of salivary flow (as would occur during the oral processing of food) demonstrated a greater output of salivary vitamin-binding proteins compared to resting flow, thus potentially exerting an assimilatory function. Vitamin-binding proteins were however, present in saliva at resting flow, suggesting they may contribute to the maintenance of oral homeostasis. Data presented in this thesis suggest the vitamin B12-binding protein; haptocorrin, exerted a bacteriostatic effect on P. gingivalis by sequestering physiologically active analogues of vitamin B12.
|Date of Award
|1 May 2019
|Guy Carpenter (Supervisor) & Blanaid Daly (Supervisor)