[Mutations and alterations in the transmission of genetic information in Drosophila melanogaster by injection of diapausing chrysalids (Pieris brassicae) treated with pterins].
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The combined content of biopterin and he separate folic acid content of human urine have been quantitated by phase-selective alternating-current stripping voltammetry at the static mercury drop electrode. The use of disposable C18 cartridge allowed the samples to be separated into two fractions, one containing biopterin and neopterin and the other folic acid. The average concentration of biopterin and neopterin together was 704 ng ml-1; precision, 6.6% (RSD, n=7); mean recovery, 96%. The average concentration of folic acid was 836 ng ml-1; precision, 8.2% (RSD, n=8); mean recovery, 91%.
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Plasma tryptophan and other putative amino acids, cortisol, folate and vitamin B12 and urinary biopterin (B) and neopterins (N) were measured in three groups of women: 62 women in the early postpartum period, 23 pregnant and 38 non-gravid controls. Sixty-two postpartum women were screened for depression by the Edinburgh postnatal depression scale (EPDS) on day 7 after delivery. Postpartum women had significantly lower tryptophan, vitamin B12 and significantly greater levels of cortisol, folate, neopterins and biopterins than controls. Comparisons between women who were classified on the EPDS as cases and non-cases revealed only a statistically significant difference for lower N:B (P<0.01) and lower folate (P<0.01) ratio in cases than non-cases. Multiple regression analysis showed a significant contribution for low tryptophan to increased EPDS which also showed significant correlations with low methionine, low tyrosine, low N:B ratio and high vitamin B12.
Urinary excretion of neopterins and biopterins was measured in 23 patients with severe depression before and after receiving electroconvulsive therapy (ECT) and 26 healthy control subjects. Patients with psychotic depression and those responding to ECT had neopterin:biopterin (N:B) ratio significantly higher than controls before commencing ECT and positive therapeutic response was associated with reduction of N:B ratio towards control values. As a raised N:B ratio implies failure to convert neopterin to biopterin it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive disorders. The N:B ratio may be a marker for certain depressive subtypes and response to ECT.
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Two mechanisms for facilitating hydride ion transfer from NADPH involving preprotonation of the pteridine rings of the dihydrofolate reductase substrates folate and dihydrofolate have been investigated by ab initio quantum mechanical methods. Protonation energies and effective solution pKas have been calculated for four protonated forms, three of which are nonpreferred in aqueous solution and therefore not directly accessible to experimental study. The pattern and degree of redistribution of the positive charge over the component rings of the N-heterobicyclic pi-system in these protonated forms have been analyzed in terms of changes in the electron populations of the ring atoms and total ring charges. The effects of such changes in promoting hydride ion transfer to C7 in folate and C6 in dihydrofolate have been evaluated by considering the extent of development of partial carbonium ion character at these carbon atoms and also the degree of electron deficiency in the pyrazine ring as a whole. The results illustrate that perturbations due, for instance, to protonation may be propagated by pi-electron coupling effects over medium-range distances of 4-6 A across the pteridine ring. The two mechanisms have been assessed in terms of the calculated absolute and relative pKas of the protonated species taking into account experimental information regarding possible stabilization of these forms in the enzyme active site and also the effectiveness of the various protonations in assisting the hydride ion transfer step. Judged against these criteria, the theoretical results favor the generally proposed mechanism involving preprotonation of N8 in folate and N5 in dihydrofolate. However, some support was also found for the alternative novel mechanism involving O4-protonation of both folate and dihydrofolate.