GSNO (S-nitrosoglutathione) is emerging as a key regulator in NO signalling as it is in equilibrium with S-nitrosated proteins. Accordingly, it is of great interest to investigate GSNO metabolism in terms of competitive pathways and redox state. The present study explored ADH3 (alcohol dehydrogenase 3) in its dual function as GSNOR (GSNO reductase) and glutathione-dependent formaldehyde dehydrogenase. The glutathione adduct of formaldehyde, HMGSH (S-hydroxymethylglutathione), was oxidized with a k(cat)/K(m) value approx. 10 times the k(cat)/K(m) value of GSNO reduction, as determined by fluorescence spectroscopy. HMGSH oxidation in vitro was greatly accelerated in the presence of GSNO, which was concurrently reduced under cofactor recycling. Hence, considering the high cytosolic NAD(+)/NADH ratio, formaldehyde probably triggers ADH3-mediated GSNO reduction by enzyme-bound cofactor recycling and might result in a decrease in cellular S-NO (S-nitrosothiol) content in vivo. Formaldehyde exposure affected S-NO content in cultured cells with a trend towards decreased levels at concentrations of 1-5 mM, in agreement with the proposed mechanism. Product formation after GSNO reduction to the intermediate semimercaptal responded to GSH/GSNO ratios; ratios up to 2-fold allowed the spontaneous rearrangement to glutathione sulfinamide, whereas 5-fold excess of GSH favoured the interception of the intermediate to form glutathione disulfide. The sulfinamide and its hydrolysis product, glutathione sulfinic acid, inhibited GST (glutathione transferase) activity. Taken together, the findings of the present study provide indirect evidence for formaldehyde as a physiological trigger of GSNO depletion and show that GSNO reduction can result in the formation of GST inhibitors, which, however, is prevented under normal cellular redox conditions.

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This article is about the status of, and the relation between, sentence type and sentence mood. The study concerns only declarative and interrogative sentences.Our aim is first to show that sentence mood as the semantic counterpart of sentence type must not-as is usually assumed-be a propositional attitude of the speaker. Starting from a consistent syntactic-semantic theoretical framework, we shall try to fortify the assumption that the sentence moods of declarative and interrogative sentence types are the semantic characterizations of a syntactic D-strueture feature + w in the leftmost position of the sentence. The declarative sentence mood consists of the existential binding of the event variable, this variable in turn being part of the propositional content of the sentence. The sentence moods of yes/no and constituent interrogative sentence types on the other hand are characterized respectively by the operator OPEN and a wh-phrase including the operator OPEN, both taking the semantic form of the declarative sentence in their scope.Our aim is second to relate sentence mood thus described to the syntax and semantics of sentence adverbiale and modal particles.We shall finally account for the performative utterances. It will be shown that performative utterances in the proposed framework are direct speech acts.