Lipofuscin Formation Catalyzed by the Milk Protein ß-Lactoglobulin: Lysine Residues in Cycloretinal Synthesis.

Lipofuscins are toxic autofluorescent byproducts of the visual cycle. The accumulation of lipofuscins such as cycloretinal in the retina is thought to play a role in the progression of age-related macular degeneration (AMD). Intriguingly, the milk protein ß-lactoglobulin (BLG) can promote the cyclodimerization of all-trans-retinal to cycloretinal both in vitro and in vivo. Here, site-directed mutagenesis of BLG and mass spectrometric analysis with substrate analogues demonstrate that lysine residues play a key role in catalysis. It is also shown that catalytic activity necessitates the presence of a physical binding site and cannot be mediated by a peptide chain. These studies provide insight into the mechanism of the cyclodimerization process and provide a model system for biocatalysis and biosynthesis of cycloretinal in vivo. In the long term, these studies may pave the way for drug development and inhibitor design as an early treatment regimen for AMD.

Weight effects of antidiabetic agents.

INTRODUCTION: Obesity and diabetes are on the rise, which remains a continuous health concern worldwide. It is important to consider weight effects of antidiabetic agents prior to initiation as different antidiabetic agents impact weight differently. Areas covered: New agents to treat diabetes, glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors, have emerged over recent years that have been shown to result in weight reduction. Unfortunately, other antidiabetic medications used can cause weight gain such as with insulin, sulfonylureas, and thiazolidediones while some remain weight neutral (metformin and dipeptidyl peptidase-4 inhibitors). The weight effects of these antidiabetic medications described are from select relevant guidelines, clinical trials, reviews, and meta-analysis found through PubMed and Ovid databases up to July 2017. Expert commentary: This article summarizes the current evidence available on the weight effects of these agents in patients with diabetes. Evaluating potential risks, such as weight gain, with potential benefits, such as improvement in glycemic control, will help with designing optimal therapeutic diabetes regimens.