Applications of Metabolomics in Calcium Metabolism Disorders in Humans

Abstract

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

Keywords: biomarkers; hypercalcemia; hypocalcemia; mass spectrometry; metabolites; metabolomics; parathyroid gland.

Figure 1

Metabolites altered in calcium metabolism disorders detected in metabolomics studies. (A) shows pie chart illustrating distribution of all metabolites across different classes, while (B) shows a table with distribution of metabolites across different classes with the stratification for different calcium metabolism disorders. The numbers reflect the number of metabolites assigned to the particular class.

Figure 2

Characterization of metabolites altered in PHPT. (A) shows the main pathways, built for the discriminating metabolites reported in review publications. (B) shows pie chart, illustrating the distribution of the discriminating metabolites across different metabolite classes.

Figure 3

Characterization of metabolites altered in SHPT. (A) shows the main pathways, built for the discriminating metabolites reported in review publications. (B) shows pie chart, illustrating the distribution of the discriminating metabolites across different metabolite classes.

Figure 4

Characterization of metabolites altered in calcium deficiency. (A) shows the main pathways, built for the discriminating metabolites reported in review publications. (B) shows pie chart, illustrating the distribution of the discriminating metabolites across different metabolite classes.

Figure 5

Characterization of metabolites altered in osteopenia and osteoporosis. (A) shows the main pathways, built for the discriminating metabolites reported in review publications. (B) shows pie chart, illustrating the distribution of the discriminating metabolites across different metabolite classes.

Figure 6

Characterization of metabolites altered in vitamin D3 deficiency. (A) shows the main pathways, built for the discriminating metabolites reported in review publications. (B) shows pie chart, illustrating the distribution of the discriminating metabolites across different metabolite classes. Second largest group of metabolites are Carboxylic acids and derivatives, followed by Phenols, Indoles and derivatives and Organooxygen compounds. The location of these metabolites in the metabolic pathways showed high alterations in the amino acids’ metabolism. Tryptophan metabolism, Arginine biosynthesis and Valine, leucine and isoleucine biosynthesis together with Amino-tRNS biosynthesis were the most impacted pathways.