Pterin-4α-carbinolamine dehydratase in rat brain

Depaepe, Vanessa; Cuvelier, Laetitia; Thöny, Beat; Résibois, A.

doi:10.1016/s0169-328x(99)00297-1

Cited by 8 publications

(1 citation statement)

References 41 publications

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“…Positive nerve cells occur in myenteric ganglia of the whole gastrointestinal tract and in the intestinal submucosal ganglia. The prominent nuclear immunoreactivity found in all neural crest, but also in other cell types that do not express either HNF-1α or aromatic amino acid hydrolases, argues in favour of a novel, as yet unknown, function of the protein [79,80].…”

Section: Pcd/dcohmentioning

confidence: 99%

Tetrahydrobiopterin biosynthesis, regeneration and functions

Thöny¹,

AUERBACH²,

Blau³

2000

Biochem. J.

Self Cite

393

368

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Tetrahydrobiopterin (BH(4)) cofactor is essential for various processes, and is present in probably every cell or tissue of higher organisms. BH(4) is required for various enzyme activities, and for less defined functions at the cellular level. The pathway for the de novo biosynthesis of BH(4) from GTP involves GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase and sepiapterin reductase. Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and dihydropteridine reductase. Based on gene cloning, recombinant expression, mutagenesis studies, structural analysis of crystals and NMR studies, reaction mechanisms for the biosynthetic and recycling enzymes were proposed. With regard to the regulation of cofactor biosynthesis, the major controlling point is GTP cyclohydrolase I, the expression of which may be under the control of cytokine induction. In the liver at least, activity is inhibited by BH(4), but stimulated by phenylalanine through the GTP cyclohydrolase I feedback regulatory protein. The enzymes that depend on BH(4) are the phenylalanine, tyrosine and tryptophan hydroxylases, the latter two being the rate-limiting enzymes for catecholamine and 5-hydroxytryptamine (serotonin) biosynthesis, all NO synthase isoforms and the glyceryl-ether mono-oxygenase. On a cellular level, BH(4) has been found to be a growth or proliferation factor for Crithidia fasciculata, haemopoietic cells and various mammalian cell lines. In the nervous system, BH(4) is a self-protecting factor for NO, or a general neuroprotecting factor via the NO synthase pathway, and has neurotransmitter-releasing function. With regard to human disease, BH(4) deficiency due to autosomal recessive mutations in all enzymes (except sepiapterin reductase) have been described as a cause of hyperphenylalaninaemia. Furthermore, several neurological diseases, including Dopa-responsive dystonia, but also Alzheimer's disease, Parkinson's disease, autism and depression, have been suggested to be a consequence of restricted cofactor availability.

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Section: Pcd/dcohmentioning

confidence: 99%