AAs metabolism is associated with many diseases [10]. Under normal physiological conditions, the concentration of AAs and their metabolites are mantained at stable levels [11]. Thus, it is critical to detect any change of these molecules to predict disease insurgence and course [12]. Alterations in AAs can also affect body growth and development. KBD is indeed linked several metabolic alteerations in the body [13]. The detection of changes in AAs and/or their metabolites might be a useful biomarker for disease diagnosis such as KBD.
Research has shown that the establishment and development of OA are associated with inflammation and alterations in AAs metabolism and profiles [14]. In this study, we determined the serum AAs of KBD adolescent employing UPLC/Q-TOF-MS technology, and found 12 different AAs and their metabolites, including His, Glu, Trp, Cys, Etn, Tau, Thr, ASP, Pro, Ile, Hyp, 5-HT. These AAs and their metabolites are involved in several biological processes including aminoacyl-tRNA biosynthesis, histidine, arginine and praline metabolism, alanine, aspartate and glutamate metabolism, glycine, serine and theronine metabolism. ASP is a key driver of AA metabolism and energy metabolism. Glu is involved in histidine, arginine and praline metabolism, alanine, aspartate and glutamate metabolism. His, Cys, Thr, and Pro are also involved in AA metabolism. These processes link amino acid metabolism with carbohydrate metabolism through the exchange of sugar [6].What’s more, some final metabolites have the potential function of the biomarkers of KBD.
While the etiology of KBD remains elusive, three major environmental factors have been identified as being associated with this disease: selenium deficiency, grain contamination by mycotoxin-producing fungi, and water contamination by organic materials such as fulvic acid [15]. The main pathophysiological changes of KBD include chondrocyte necrosis, ageing and dedifferentiation, type II collagen degradation and loss of proteoglycans [16]. Glu and Cys are involved in synthesis of GSH. GSH, belonging to selenoproteins, plays a very important role in the pathogenesis of KBD [17]. Decreased selenoproteins would unbalance the redoxsystem, which could result in apoptosis and necrosis of chondrocytes and, thus, play a crucial role in the pathogenesis of KBD [18]. Mycotoxin contamination (e.g., T-2 toxin) of locally produced cereals may increase the levels of reactive oxygen species and free radicals in the body, which may damage chondrocytes, disturb the extracellular matrix and induce excessive apoptosis and necrosis of chondrocytes in KBD patients [18]. Etn indicated the abnormality of lipid metabolism and oxidative stress [19].Trp plays an important role in regulating the autoimmune [20]. 5-HT, a neurotransmitter, was formed by Trp [21]. Ile might also be effective to attenuate the progression of OA by inhibiting NO synthesis [22]. His can be converted to intermediates of the tricarboxylic acid (TCA) cycle. His, as well as their relevant metabolic pathways, might undergo pathological alterations during the development of OA [23]. Thr is reported to regulate epithelial cell migration and proliferation, cell differentiation, restoration of epithelial barrier functions, modulation of cell apoptosis and proteoglycan synthesis [24]. Moreover, Tau, a sulfur-containing AA, exists in the body in free form and, while not directly involved in protein synthesis, it regulates the metabolism of AAs. Taurine plays an important role in bone metabolism, can promotes the production of osteoblasts [25] and inhibits the formation of osteoclasts [26].Tau could promote chondrocyte proliferation, maintain its phenotype, and increase the expression of type II collagen [27]. Knee OA cartilage is characterized by a decrease in Asp-RR, possibly due to increase in collagen type II synthesis [28]. Pro are the main components of type II collagen in cartilage. The increase of Pro suggested that type II collagen could have been partly broken down [29], which might aggravate cartilage degenation.
Because of the low number of KBD cases, one of the limitations of this study is the small sample size. Nevertheless, this investigation provided new clues into the KBD pathogenesis. Biological relevance of these AAs on KBD developing and occurrence were unclear. Many genes encoding enzymes involved AAs metabolism were up-regulated during the KBD development. Further research is needed to probe the AAs changes in KBD using large size and investigating the effect on the metabolic pathways linked to these AAs.
In summary, among the 50 AAs detected using UPLC-QTOF-MS, 12 different AAs and their metabolites were found difference in serum of KBD adolescent. These AAs changes provide a new clue for KBD pathogenesis.