Fig 1: C1 metabolic pathway and characterization of R6/2 mice. A Folate, Met and BH4 cycles in plants and animals and their associated metabolism. Red lines stand for mammal specific, green lines stand for plant specific while black lines stand for both. All enzymes with protein levels examined by immunoblotting are marked in red. B mHtt protein aggregates in cortex and striatum regions were detected with anti-Htt antibody (mEM48) in 4-week-old male R6/2 and NCAR mice. C, D Quantification analysis of immunoblotting results of GTPCH, DHFR, QDPR, MS, MAT1/2A, AHCY, MTHFR, TPH2, TH, nNOS and ChAT (n = 7). The band intensity of each protein from western blotting D was normalized with ?-tubulin on the same blot. The ratio was further calculated against NCAR whose relative expression level was set as 1. All data plotted are the average (n = 7) ± SD. Only one representative western blotting of ?-tubulin is shown. Original blots of above proteins before cropping are presented in Fig. S11. E Contents of BH4 and BH2, and their ratio in brain tissues and plasma (n = 4, average ± SD). *p < 0.05; **p < 0.01. ***p < 0.001. Abbreviations used for enzymes: AHCY S-adenosylhomocysteine hydrolase, ChAT choline acetyltransferase, DHFR dihydrofolate reductase, GTPCH GTP cyclohydrolase I, MAT1/2A methionine adenosyltransferase, MS methionine synthase, MTHFR methylene-tetrahydrofolate reductase, nNOS neuronal nitric oxide synthase, QDPR quinoid dihydropteridine reductase, TH tyrosine hydroxylase (Tyr), TPH2 tryptophan hydroxylase
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