Rate-Limiting Enzymes in Cardiometabolic Health and Aging in Humans.

INTRODUCTION: Rate-limiting enzymes (RLEs) are innate slow points in metabolic pathways, and many function in bio-processes related to nutrient sensing. Many RLEs carry causal mutations relevant to inherited metabolic disorders. Because the activity of RLEs in cardiovascular health is poorly characterized, our objective was to assess their involvement in cardiometabolic health and disease and where altered biophysical and biochemical functions can promote disease. METHODS: A dataset of 380 human RLEs was compared to protein and gene datasets for factors likely to contribute to cardiometabolic disease, including proteins showing significant age-related altered expression in blood and genetic loci with variants that associate with common cardiometabolic phenotypes. The biochemical reactions catalyzed by RLEs were evaluated for metabolites enriched in RLE subsets associating with various cardiometabolic phenotypes. Most significance tests were based on Z-score enrichment converted to p values with a normal distribution function. RESULTS: Of 380 RLEs analyzed, 112 function in mitochondria, and 53 are assigned to inherited metabolic disorders. There was a depletion of RLE proteins known as aging biomarkers. At the gene level, RLEs were assessed for common genetic variants that associated with important cardiometabolic traits of LDL-cholesterol or any of the five outcomes pertinent to metabolic syndrome. This revealed several RLEs with links to cardiometabolic traits, from a minimum of 26 for HDL-cholesterol to a maximum of 45 for plasma glucose. Analysis of these GWAS-linked RLEs for enrichment of the molecular constituents of the catalyzed reactions disclosed a number of significant phenotype-metabolite links. These included blood pressure with acetate (p = 2.2 × 10-4) and NADP+ (p = 0.0091), plasma HDL-cholesterol and triglyceride with diacylglycerol (p = 2.6 × 10-5, 6.4 × 10-5, respectively) and diolein (p = 2.2 × 10-6, 5.9 × 10-6), and waist circumference with d-glucosamine-6-phosphate (p = 1.8 × 10-4). CONCLUSION: In the context of cardiometabolic health, aging, and disease, these results highlight key diet-derived metabolites that are central to specific rate-limited processes that are linked to cardiometabolic health. These metabolites include acetate and diacylglycerol, pertinent to blood pressure and triglycerides, respectively, as well as diacylglycerol and HDL-cholesterol.

A Catalog of Natural Products Occurring in Watermelon-Citrullus lanatus.

Sweet dessert watermelon (Citrullus lanatus) is one of the most important vegetable crops consumed throughout the world. The chemical composition of watermelon provides both high nutritional value and various health benefits. The present manuscript introduces a catalog of 1,679 small molecules occurring in the watermelon and their cheminformatics analysis for diverse features. In this catalog, the phytochemicals are associated with the literature describing their presence in the watermelon plant, and when possible, concentration values in various plant parts (flesh, seeds, leaves, roots, rind). Also cataloged are the chemical classes, molecular weight and formula, chemical structure, and certain physical and chemical properties for each phytochemical. In our view, knowing precisely what is in what we eat, as this catalog does for watermelon, supports both the rationale for certain controlled feeding studies in the field of precision nutrition, and plant breeding efforts for the development of new varieties with enhanced concentrations of specific phytochemicals. Additionally, improved and comprehensive collections of natural products accessible to the public will be especially useful to researchers in nutrition, cheminformatics, bioinformatics, and drug development, among other disciplines.