[Rare diseases of the maxillary sinus]. / Seltene Erkrankungen der Kieferhöhle.

BACKGROUND: Silent sinus syndrome (SSS), organized hematoma (OH), and pneumosinus dilatans (PD) are rare, usually unilateral diseases of the maxillary sinus. Due to misinterpretation, excessive diagnostics and unnecessarily aggressive surgery or a delay in diagnostics and treatment are common. OBJECTIVE: The objective of this study was to develop reasonable and comprehensible diagnostic criteria to improve diagnosis and treatment of these rare diseases. METHODS: In this retrospective study, all patients treated for SSS, OH, and PD from 2012 to 2019 were identified. Patient history, diagnostic tests and results, and postoperative course were analyzed and compared with the available literature. RESULTS: During the study period, 7 patients with SSS, 3 patients with PD, and 2 patients with OH were treated and available for follow-up. Comparison of these patients with the literature allowed us to develop diagnostic criteria. CONCLUSION: Medical history combined with endoscopic and radiologic criteria should improve preoperative diagnosis of these three rare diseases of the maxillary sinus and help to distinguish them from other differential diagnoses. This approach should minimize morbidity for the patients.

Biosynthesis of riboflavin. Single turnover kinetic analysis of GTP cyclohydrolase II.

GTP cyclohydrolase II catalyzes the conversion of GTP into a mixture of 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (Compound 2), formate, and pyrophosphate. Moreover, GMP was recently shown to be formed as a minor product. The major product (Compound 2) serves as the first committed intermediate in the biosynthesis of the vitamin, riboflavin. Numerous pathogenic microorganisms are absolutely dependent on endogenous synthesis of riboflavin. The enzymes of this pathway are therefore potential drug targets, and mechanistic studies appear relevant for development of bactericidal inhibitors. Pre-steady state quenched flow analysis of GTP cyclohydrolase II shows the rate-determining step to be located at the beginning of the reaction sequence catalyzed by the enzyme. Thus, GTP is consumed at a rate constant of 0.064 s(-1), and the reaction product, Compound 2, is formed at an apparent rate constant of 0.062 s(-1). Stopped flow experiments monitored by multiwavelength photometry are well in line with these data. 2-Amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone triphosphate can serve as substrate for GTP cyclohydrolase II but does not fulfill the criteria for a kinetically competent intermediate. A hypothetical reaction mechanism involves the slow formation of a phosphoguanosyl derivative of the enzyme under release of pyrophosphate. The covalently bound phosphoguanosyl moiety is proposed to undergo rapid hydrolytic release of formate from the imidazole ring and/or hydrolytic cleavage of the phosphodiester bond.

Biosynthesis of pteridines. Stopped-flow kinetic analysis of GTP cyclohydrolase I.

GTP cyclohydrolase I catalyzes a mechanistically complex ring expansion affording dihydroneopterin triphosphate from GTP. The inherently slow enzyme reaction was studied under single turnover conditions monitored by multiwavelength ultraviolet spectroscopy. The spectroscopic data array was subjected to singular value decomposition and thereby shown to comprise six significant linearly independent optical processes. The data were fitted to a model of six consecutive unimolecular reaction steps where the first was considered to be reversible. The rate-limiting step was shown to occur rather late in the reaction sequence.

Biosynthesis of riboflavin: studies on the mechanism of GTP cyclohydrolase II.

GTP cyclohydrolase II catalyzes the first committed reaction in the biosynthesis of the vitamin riboflavin. The recombinant enzyme from Escherichia coli is shown to produce 2,5-diamino-6-beta-ribosylamino-4(3H)-pyrimidinone 5'-phosphate and GMP at an approximate molar ratio of 10:1. The main product is subject to spontaneous isomerization affording the alpha-anomer. (18)O from solvent water is incorporated by the enzyme into the phosphate group of the 5-aminopyrimidine derivative as well as GMP. These data are consistent with the transient formation of a covalent phosphoguanosyl derivative of the enzyme. Subsequent ring opening of the covalently bound nucleotide followed by hydrolysis of the phosphodiester bond could then afford the pyrimidine type product. The hydrolysis of the phosphodiester bond without prior ring opening could afford GMP. The enzyme reaction is cooperative with a Hill coefficient of 1.3. Inhibition by pyrophosphate is competitive. Inhibition by orthophosphate is partially uncompetitive at low concentration and competitive at concentrations above 6 mm.

Ring opening is not rate-limiting in the GTP cyclohydrolase I reaction.

GTP cyclohydrolase I catalyzes a mechanistically complex ring expansion affording dihydroneopterin triphosphate and formate from GTP. Single turnover quenched flow experiments were performed with the recombinant enzyme from Escherichia coli. The consumption of GTP and the formation of 5-formylamino-6-ribosylamino-2-amino-4(3H)-pyrimidinone triphosphate, formate, and dihydroneopterin triphosphate were determined by high pressure liquid chromatography analysis. A kinetic model comprising three consecutive unimolecular steps was used for interpretations where the first intermediate, 5-formylamino-6-ribosylamino-2-amino-4(3H)-pyrimidinone 5'-triphosphate, was formed in a reversible reaction. The rate constant k(1) for the reversible opening of the imidazole ring of GTP was 0.9 s(-1), the rate constant k(3) for the release of formate from 5-formylamino-6-ribosylamino-2-amino-4(3H)-pyrimidinone triphosphate was 2.0 s(-1), and the rate constant k(4) for the formation of dihydroneopterin triphosphate was 0.03 s(-1). Thus, the hydrolytic opening of the imidazole ring of GTP is rapid by comparison with the overall reaction.

Biosynthesis of terpenoids: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from tomato.

The putative catalytic domain (residues 81-401) of a predicted tomato protein with similarity to 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase of Escherichia coli was expressed in a recombinant E. coli strain. The protein was purified to homogeneity and was shown to catalyze the phosphorylation of the position 2 hydroxy group of 4-diphosphocytidyl-2-C-methyl-d-erythritol at a rate of 33 micromol small middle dotmg(-1) small middle dotmin(-1). The structure of the reaction product, 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate, was established by NMR spectroscopy. Divalent metal ions, preferably Mg(2+), are required for activity. Neither the tomato enzyme nor the E. coli ortholog catalyzes the phosphorylation of isopentenyl monophosphate.

Histidine 179 mutants of GTP cyclohydrolase I catalyze the formation of 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate.

GTP cyclohydrolase I catalyzes the conversion of GTP to dihydroneopterin triphosphate. The replacement of histidine 179 by other amino acids affords mutant enzymes that do not catalyze the formation of dihydroneopterin triphosphate. However, some of these mutant proteins catalyze the conversion of GTP to 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone 5'-triphosphate as shown by multinuclear NMR analysis. The equilibrium constant for the reversible conversion of GTP to the ring-opened derivative is approximately 0.1. The wild-type enzyme converts the formylamino pyrimidine derivative to dihydroneopterin triphosphate; the rate is similar to that observed with GTP as substrate. The data support the conclusion that the formylamino pyrimidine derivative is an intermediate in the overall reaction catalyzed by GTP cyclohydrolase I.

Complementation of the fol2 deletion in Saccharomyces cerevisiae by human and Escherichia coli genes encoding GTP cyclohydrolase I.

Saccharomyces cerevisiae is so far the only organism where a knock-out mutant in the gene encoding GTP cyclohydrolase I (FOL2) has been obtained. GTP cyclohydrolase I controls the de novo biosynthetic pathway of tetrahydrobiopterin and folic acid. Since deletion of yeast FOL2 leads to a recessive auxotrophy for folinic acid, we used a yeast fol2Delta mutant for an in vivo functional assay of heterologous GTP cyclohydrolases I. We show that the GTP cyclohydrolase I, encoded either by the E. coli folE gene or by the human cDNA, complements the yeast fol2Delta mutation by restoring folate prototrophy. Furthermore the folE-3x allele of the E. coli gene, carrying three base substitutions, failed to complement the yeast fol2Delta defect. This allele behaved as a negative semidominant to the wild type folE and, when overexpressed, completely abolished complementation of fol2Delta by folE. Thus, the yeast fol2 null mutant is a suitable system to characterize mutations in genes encoding GTP cyclohydrolase I.

Biosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase.

GTP cyclohydrolase I catalyzes a ring expansion affording dihydroneopterin triphosphate from GTP. [1',2',3',4',5'-13C5, 2'-2H1]GTP was prepared enzymatically from [U-13C6]glucose for use as enzyme substrate. Multinuclear NMR experiments showed that the reaction catalyzed by GTP cyclohydrolase I involves the release of a proton from C-2' of GTP that is exchanged with the bulk solvent. Subsequently, a proton is reintroduced stereospecifically from the bulk solvent. This is in line with an Amadori rearrangement mechanism. The proton introduced from solvent occupies the pro-7R position in the enzyme product. The data also confirm that the reaction catalyzed by pyruvoyltetrahydropterin synthase results in the incorporation of solvent protons into positions C-6 and C-3' of the enzyme product. On the other hand, the reaction catalyzed by sepiapterin reductase does not involve any detectable incorporation of solvent protons into tetrahydrobiopterin.