Biopteriinin synteesistä

https://www.ncbi.nlm.nih.gov/pubmed/6150460

Pediatrics. 1984 Dec;74(6):1004-11.

Biopterin synthesis defects: problems in diagnosis.

Hoganson G, Berlow S, Kaufman S, Milstien S, Schuett V, Matalon R, Naylor E, Seifert W.

Hyperphenylalaninemia due to a biopterin synthesis defect was detected in an infant with decreased biopterin and increased neopterin levels in plasma and urine.
Tetrahydrobiopterin (BH4) administration normalized plasma phenylalanine levels.
 CSF biopterin and neurotransmitter metabolite levels were normal and with the infant's normal growth and development suggest that the defect in biopterin synthesis did not affect CNS biopterin metabolism.
Comparison of plasma and urine pterin levels from this patient with levels reported in patients who have neurologic complications fails to reveal differences that would distinguish patients at risk for neurologic problems. CSF pterin and neurotransmitter levels may correlate with neurologic function in these patients. CSF pterin and neurotransmitter determinations should be performed prior to initiation of neurotransmitter precursor and BH4 replacement therapies in patients who were determined to have biopterin synthesis defect(s).

PMID:

6150460

[Indexed for MEDLINE]

http://www.sciencedirect.com/topics/neuroscience/biopterin
Ilmeinen kognition kehittyminen essentielleistä tarpeista  ihmiskunnalla  toimii  pohjageneraattorina  biopteriinin muodostukselle jollioin tuottuu mm dopa, adrenaliini, noradrenaliini ja kilpirauhashormoneille tärkeä tyrosiinikin paremmin koentsyymin tehostamana.
Tähän  generoituun biopteriiniin antaa tehoa  foolihappo, koska  se  voi uudistaa biopteriiin aktiivia muotoa,  joka pystyy taas  käyttämään happea siten, että ei synny aivoissa superoksidianionia.

Nonnutrients

Martin Kohlmeier, in Nutrient Metabolism (Second Edition), 2015

Regulation

Biopterin status is predominantly controlled by modulation of GTP cyclohydrolase 1 expression and activity. Gamma-interferon and other cytokines increase biopterin production by inducing GTP cyclohydrolase 1 (Thöny et al., 2000). Glucocorticoids prevent cytokine-mediated induction of GTP cyclohydrolase 1 (Simmons et al., 1996), apparently via a cyclic adenosine monophosphate (cAMP)–-mediated signaling cascade (Ohtsuki et al., 2002). Food deprivation of animals increases biopterin production and concentration in the blood (Koller et al., 1990).

Inflammation and infection tend to depress availability of biopterin in tissues, such as endothelia of small blood vessels, due to rapid oxidation of the reduced form (McNeill and Channon, 2012).

Aminoacidopathies and Organic Acidopathies, Mitochondrial Enzyme Defects, and Other Metabolic Errors

Generoso G. Gascon, ... Bruce Cohen, in Textbook of Clinical Neurology (Third Edition), 2007

PATHOGENESIS AND PATHOPHYSIOLOGY

Defective synthesis of biopterin (BH₄) causes disruption in several biochemical functions. 

Deficiencies of the first two steps, that is, guanosine triphosphate cyclohydrolase (GTP‐CH) and 6‐pyruvoyltetra‐hydropterin synthase (6PTS), are known as synthetic defects. The hydroxylase reacts with BH₄, converting it to its hydroxy form 4α‐carbinolamine, which is then dehydrated by primapterin carbinolamine dehydratase (PCD) to quininoid dihydrobiopterin, which is labile and must be reduced back to BH₄ through a reaction that uses reduced nicotinamide adenine dinucleotide and is catalyzed by dihydropteridine reductase (DHPR).

The deficiencies of the latter two enzymes are known as recycling defects. Because primapterin is excreted in PCD deficiency, the disease is also called primapterinuria. 

BH₄ is a cofactor for enzymes of the initial step in dopamine and serotonin synthesis; when it is not available, neurotransmitter and autonomic function, both in the CNS and periphery, are disturbed.

 In addition, BH₄ is a cofactor for the generation of nitric oxide in the CNS, which is a neurotransmitter/modulator. (verisuonten dilataatiotgekijä, estää verisuonikollapsia)

 Deficiency of BH₄ causes

•  severe autonomic irregularities and
•  mental retardation and, ultimately,
•  is not compatible with life

• . Severe cardiopulmonary dysrhythmia,
•  fluctuating blood pressure,
•  sleep irregularities,
•  and early unexpected death

 may be explained by these considerations. 

Because 4α‐carbinolamine can be spontaneously dehydrated, PCD deficiency does not cause severe disease.

• In BH₄‐dependent PKU, neurological manifestations are severe in the presence of mild hyperphenylalaninemia, suggesting that trace BH₄ levels are sufficient to promote the phenylalanine hydroxylase reaction in liver but not high enough for adequate hydroxylation of tyrosine and tryptophan in the CNS.
•   All four diseases are inherited as autosomal recessive.
•  The location of their genes is shown in Table 31‐3.

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