Effect of L-Carnitine on Amino Acid Metabolism in Elderly Patients Undergoing Regular Hemodialysis.

INTRODUCTION: Among patients regularly undergoing hemodialysis, hypocarnitinaemia often develops as a consequence of inadequate dietary intake, reduced synthesis in the body, and considerable losses during hemodialysis. OBJECTIVES: To evaluate the effects of L-carnitine supplementation on patients with end-stage kidney disease (ESKD) who underwent hemodialysis. METHODS: Thirty-one patients with ESKD, comprising 18 men and 13 women, with a median age of 72 (range 58-89) years, who underwent regular hemodialysis received treatment with L-carnitine for 1 year. The total and free carnitine, acylcarnitine, and amino acids (AA) levels before and after L-carnitine treatment were analyzed, and the blood biochemistry results and clinical profiles of the subjects were compared before and after treatment. RESULTS: The median (interquartile range [IQR]) serum total and free carnitine and acylcarnitine levels significantly increased from 34.5 (28.2-44.3), 20.9 (15.8-27.6), and 14.1 (11.2-17.6) µmol/L, respectively to 407.4 (371.6-493.5), 270.2 (228.3-316.0), and 155.0 (136.1-168.5) µmol/L, respectively, after treatment (all p < 0.001). The median (IQR) blood valine, tyrosine, phenylalanine, and citrulline levels increased from 0.94 (0.80-1.09), 0.45 (0.39-0.55), 0.61 (0.56-0.79), and 1.04 (0.79-1.26) mg/dL, respectively to 1.24 (1.13-1.54), 0.76 (0.62-0.85), 0.90 (0.70-1.04), and 1.22 (0.92-1.39) mg/dL, respectively, following L-carnitine treatment (p < 0.001, p < 0.001, p = 0.002, and p = 0.030, respectively); however, the median (IQR) blood arginine level decreased from 0.20 (0.13-0.24) to 0.09 (0.06-0.14) mg/dL after treatment (p < 0.001). The median (IQR) percentage fractional shortening (41.5 vs. 41.9%; p = 0.012) and left ventricular ejection fraction (65.2 vs. 67.3%; p = 0.036) increased significantly following treatment. CONCLUSIONS: L-Carnitine increased the blood acylcarnitine levels, enhanced fatty acid metabolism, and affected AAs metabolism; this may be beneficial for energy production within the cardiac and skeletal muscles.

Biotin-responsive basal ganglia disease: a case diagnosed by whole exome sequencing.

Using whole exome sequencing, we confirmed a diagnosis of biotin-responsive basal ganglia disease (BBGD) accompanied by possible Kawasaki Disease. BBGD is an autosomal-recessive disease arising from a mutation of the SLC19A3 gene encoding the human thiamine transporter 2 protein, and usually manifests as subacute to acute encephalopathy. In this case, compound heterozygous mutations of SLC19A3, including a de novo mutation in one allele, was the cause of disease. Although a large number of genetic neural diseases have no efficient therapy, there are several treatable genetic diseases, including BBGD. However, to achieve better outcome and accurate diagnosis, therapeutic analysis and examination for disease confirmation should be done simultaneously. We encountered a case of possible Kawasaki disease, which had progressed to BBGD caused by an extremely rare genetic condition. Although the prevalence of BBGD is low, early recognition of this disease is important because effective improvement can be achieved by early biotin and thiamine supplementation.

Glycine regulates proliferation and differentiation of salivary-gland-derived progenitor cells.

Amino acids have various physiological activities that influence processes such as intestinal regeneration, EGF secretion, protein synthesis, and cell growth. Salivary glands are exposed to nutrients that influence their proliferation and regeneration. Glycine is included in saliva in large quantities and reportedly has important roles in antibacterial activities and the inhibition of tumor growth and as a precursor of nucleotide synthesis in cell proliferation. We have investigated the effects of glycine on the proliferation and differentiation of salivary glands by using mouse salivary-gland-derived progenitor (mSGP) cells. In cultures of mSGP cells, cell proliferation is suppressed in the presence of glycine, whereas it is promoted by its removal. Glycine promotes three-dimensional formations of mSGP cells, which are negative for immature markers and positive for differentiation markers. In cell-cycle analysis, cell-cycle progression is delayed at the S-phase by glycine supplementation. Glycine also suppresses the phosphorylation of p42/p44MAPK. These results suggest that glycine suppresses the proliferation and promotes the differentiation of mSGP cells, and that it has inhibitory effects on growth factor signaling and cell-cycle progression. Glycine might therefore be a physiological activator that regulates the proliferation and differentiation of salivary glands.