PubMed · 11514656
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N R Pinninti, D S Mahajan. 2001. Gabapentin-associated aggression.. https://doi.org/10.1176/jnp.13.3.424
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The toxicity of acetylacetone has been demonstrated in various studies. Little is known, however, about metabolic pathways for its detoxification or mineralization. Data presented here describe for the first time the microbial degradation of acetylacetone and the characterization of a novel enzyme that initiates the metabolic pathway. From an Acinetobacter johnsonii strain that grew with acetylacetone as the sole carbon source, an inducible acetylacetone-cleaving enzyme was purified to homogeneity. The corresponding gene, coding for a 153 amino acid sequence that does not show any significant relationship to other known protein sequences, was cloned and overexpressed in Escherichia coli and gave high yields of active enzyme. The enzyme cleaves acetylacetone to equimolar amounts of methylglyoxal and acetate, consuming one equivalent of molecular oxygen. No exogenous cofactor is required, but Fe(2+) is bound to the active protein and essential for its catalytic activity. The enzyme has a high affinity for acetylacetone with a K (m) of 9.1 microM and a k(cat) of 8.5 s(-1). A metabolic pathway for acetylacetone degradation and the putative relationship of this novel enzyme to previously described dioxygenases are discussed.
The integrins alpha(v)beta(1), alpha(v)beta(5), alpha(v)beta(6) and alpha(v)beta(8) have all recently been shown to interact with the RGD motif of the latency-associated peptide (LAPbeta(1)) of transforming growth factor beta(1) (TGFbeta(1)), with binding to alpha(v)beta(6) and alpha(v)beta(8) leading to TGFbeta(1) activation. Previously it has been suggested that the remaining alpha(v) integrin, alpha(v)beta(3,) does not interact with LAPbeta(1). However, here we show clearly that alpha(v)beta(3) does indeed interact with the LAPbeta(1) RGD motif. This interaction is similar to other alpha(v)beta(3) ligands in terms of the cations required for adhesion, the concentrations of LAPbeta(1) required for binding and the ability of a small-molecule inhibitor of alpha(v)beta(3), SB223245, to block the interaction. Using glutathione S-transferase fusion proteins we have mapped a minimal integrin-binding loop in LAPbeta(1) and then used this approach to probe the integrin-binding properties of the equivalent loops in LAPbeta(2) and LAPbeta(3). We show that the RGD motif of LAPbeta(3) also interacts with alpha(v)beta(3), in addition to alpha(v)beta(6), alpha(v)beta(1) and alpha(v)beta(5), whereas the corresponding loop in LAPbeta(2) does not interact with these integrins. These observations therefore correct a previously reported inaccuracy in the literature. Furthermore, they are important as they link alpha(v)beta(3) and TGFbeta, which may have implications in cancer and a number of inflammatory and fibrotic diseases where expression of both proteins has been documented.
The valuable pharmaceutical polymer, hyaluronic acid, is produced industrially using the gram-positive bacterium Streptococcus zooepidemicus. Synthesis of this polymer is a significant energetic burden upon the microorganism hence the native NADH oxidase gene was cloned and overexpressed to increase the energy yield of catabolism during aerobic cultivation on glucose. Elevated NADH oxidase levels led to a decline in lactic acid generation and prevented ethanol formation, leaving acetate as the main fermentation product. Biomass yield increased due to the energy gained from the formation of acetate. Evaluation of the acetate flux control coefficient over a range of NADH oxidase expression levels revealed that acetate production was sensitive to the NADH oxidase level. However, at high NADH oxidase levels, the acetate flux was mainly influenced by another factor. The concomitant excretion of pyruvate at high NADH oxidase levels suggested that the flux through the pyruvate dehydrogenase enzyme complex was limiting the conversion of pyruvate to acetate.