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BH 4 can be produced through two pathways: de novo synthesis , regulated by the rate-limiting enzyme guanosine triphosphate cyclohydrolase I (GTPCH), or through the salvage pathway , where dihydrobiopterin (BH 2 ) is recycled back to BH 4 by dihydrofolate reductase (DHFR) (Crabtree et al., 2009b

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