RPLC Analysis Identify Unique Metabolomics Profiles Of SD...

3.1 RPLC analysis identifies unique metabolomics profiles of SD disease Untargeted metabolomics profiling of liver and brain samples from SD mice (n=3) and normal mice (n=3) were performed through RPLC. A total of 177 metabolites were found to be significantly dysregulated in mouse liver samples (p (-- removed HTML --) 0.5). Out of these 177 metabolites, 96 (54.2%) out were significantly upregulated, while 81 (45.8%) were downregulated in SD mouse liver. Similarly, a total of 112 metabolites were found to be dysregulated in mouse brain samples (p (-- removed HTML --) 0.5). Out of these 112 metabolites, 53 (47.3%) were significantly upregulated, while 59 (52.7%) were downregulated in SD mouse brain. Further, the same technology was†¦show more content†¦Similar observations were found in human hippocampus and mouse liver samples. In summary, we have identified alterations in protein catabolism and lipid metabolism, which are consistent with previous findings in MPS I and MPS VII mice [13]. Specifically, several metabolites warrant further discussions. In mouse liver samples, N-acetylgalactosamine 4-sulphate, also known as GalNAc4S, increased by 2.17 fold compared with normal controls (p0.05). N-acetylgalactosamine 4-sulphate is key component of glycosaminoglycans (GAG) including dermatan, keratan and chondroitin sulfate), and is found in elevated concentrations in the urine of MPS patients. More interestingly, since Hex enzyme may also cleave GAG, mice and cats with SD showed GAG accumulation and MPS-like phenotype [14,15]. The increase in N-acetylgalactosamine 4-sulphate may be a side effect of Hex enzyme deficiency. Significant higher total GAG levels in liver of SD mice compared with normal mice (20.7 ±2.6 vs 8.4 ±1.1 µg GAG/mg protein) were also observed (Figure 2). Therefore, GAG can be used as a novel biomarker of SD. N-Acetyl-L-aspartic acid, downregulated in hippocampus of SD patients, is a neuronal osmolyte involved in fluid balance in th e brain. N-Acetyl-L-aspartic acid is also involved in energy production from glutamate in neuronal mitochondria. Further,