Interaction of β-Lactoglobulin with Retinol and Fatty Acids and Its Role as a Possible Biological Function for This Protein: A Review

Abstract

beta-Lactoglobulin is the major whey protein in the milk of ruminants and some nonruminants, such as pigs and horses. Although beta-lactoglobulin was first isolated 60 yr ago, no function has been definitely ascribed to beta-lactoglobulin. Recent x-ray crystallographic studies have advanced knowledge of the structure of beta-lactoglobulin, which is homologous with that of retinol-binding protein and lipocalycins; the function of these proteins seems to be participation in the transport of small hydrophobic substances. By analogy, this protein has been suggested as having a role as a transporter of fatty acids and retinol. This review reassesses the function of beta-lactoglobulin in light of the large amount of information that has accrued in the last few years. In particular, this review concentrates upon studies of the binding of retinol and fatty acids to beta-lactoglobulin, including the binding constants and number of binding sites, the location of the binding sites, and the influence of chemical modifications in the interaction of the protein with both ligands. This study also describes studies of the influence of beta-lactoglobulin on several biological processes that may be relevant to the possible biological role of this protein.

The evolution of milk secretion and its ancient origins

“…As b-lactoglobulin occurs in the milks of monotremes (platypus), several marsupials (brushtail possum, wallabies and kangaroos) and at least 35 species of eutherians, it must have evolved before the divergence of these groups in the Jurassic or Cretaceous period. The discovery that b-lactoglobulin was similar in structure to retinol-binding protein (RBP) led to the hypothesis that b-lactoglobulin might have a role in the transport to the young of vitamin A, vitamin D, fatty acids, or some other essential lipophilic compounds, or may play a role in intestinal uptake of these constituents (Pervaiz and Brew, 1985;Perez and Calvo, 1995;Yang et al, 2009). However, in ruminants, vitamin A is associated with the fat globule and not b-lactoglobulin; in pigs and horses, b-lactoglobulin does not bind either retinol or fatty acids; and, in suckling pups of mice that have not been genetically modified as per Yang et al (2009), vitamin D is obviously absorbed from milk despite the absence of b-lactoglobulin or the pups would develop vitamin D deficiencies.…”

“…However, in ruminants, vitamin A is associated with the fat globule and not b-lactoglobulin; in pigs and horses, b-lactoglobulin does not bind either retinol or fatty acids; and, in suckling pups of mice that have not been genetically modified as per Yang et al (2009), vitamin D is obviously absorbed from milk despite the absence of b-lactoglobulin or the pups would develop vitamin D deficiencies. Thus, if b-lactoglobulin has any role in transport and/or intestinal uptake of these lipophilic constituents, it is neither essential nor universal (Perez and Calvo, 1995). A major problem in ascribing a functional role is that b-lactoglobulin is absent from the milks of so many mammals, including laboratory mice and rats, guinea pigs, domestic rabbits, dromedary camels, llamas and humans (Sawyer, 2003).…”

Polymorphisms of beta-lactoglobulin promoter region in three Sicilian goat breeds

“…BLG is a globular protein belonging to the lipocalin family, small proteins characterized by several properties, such as the ability to bind small hydrophobic molecules [6]. Although no clear physiological functions have been defined for BLG, a role in the transport of retinol and fatty acids has been suggested [6,7]. However, the general affinity of BLG with these hydrophobic molecules did not allow ascribing a specific role [7,8].…”

“…Although no clear physiological functions have been defined for BLG, a role in the transport of retinol and fatty acids has been suggested [6,7]. However, the general affinity of BLG with these hydrophobic molecules did not allow ascribing a specific role [7,8]. Although Chianese et al [9] detected differences in BLG content in the milk of Girgentana goat breed using HPLC analysis, no genetic variants affecting the amino acid composition have been characterized in goat [10][11][12][13], whereas a large number of variants have been reported for bovine and ovine BLG protein.…”

Study of polymorphisms in the promoter region of ovine β-lactoglobulin gene and phylogenetic analysis among the Valle del Belice breed and other sheep breeds considered as ancestors

“…It is a globular protein, belonging to the family of lipocalins, small proteins with some peculiarities, such as the ability to bind hydrophobic molecules [6]. Although no clear physiological functions have been defined for BLG, a role in the transport of retinol and fatty acids has been suggested [6,7]. However, the general affinity of BLG with these hydrophobic molecules did not allow ascribing a specific role [7,8].…”