PubMed · 6144932
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1984-06-02. Acrylonitrile.. https://pubmed.ncbi.nlm.nih.gov/6144932/
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Interaction of n-butyric acid with dialyzed nitrile hydratase from Brevibacterium R312, which is characterized by a charge-transfer band at 680 nm and EPR signals typical of a low-spin Fe(III) with delta g = 0.22, leads to a form displaying different spectral properties (lambda = 710 nm, delta g = 0.31). Butyric acid also acts as a competitive inhibitor of nitrile-hydratase-catalyzed hydration of acrylonitrile with a Ki value of 0.9 mM. Formation of the complex between the enzyme and butyric acid is highly dependent on the concentration of the latter and on pH. When stored with high levels of butyric acid, nitrile hydratase is completely inactive. The active uncomplexed enzyme is restored under the high dilution conditions used for the enzymatic assays, while the complexed form is favored at acidic pH and is not formed at pH above 8. Furthermore, the inhibitory potency of butyric acid decreases upon increasing pH (IC50 increases from 0.8 mM at pH 6.2 to 12 mM at pH 8.2). These data show that nitrile hydratase interacts with the acid form of butyric acid with a high affinity (Ki' approximately 4 microM at pH 7.2). At pH < 3, the visible spectrum of the enzyme disappears, presumably because of demetallation, whereas that of the complex exhibits a charge-transfer band shifted to 800 nm, the presence of butyric acid preventing nitrile hydratase from demetallation. Other linear carboxylic acids such as valeric and hexanoic acids behave similarly; they act as inhibitors of nitrile hydratase and protect the enzyme during storage. A structure of the nitrile hydratase active site interacting with butyric acid is tentatively proposed in which the latter is hydrogen-bonded to the Fe(III)-OH moiety. This interaction between butyric acid and nitrile hydratase should be considered when deducing the nature of nitrile hydratase active site and mechanisms, from spectral and enzymatic data, since most results published previously have been obtained on nitrile hydratase containing large amounts of butyric acid and interpreted without taking into account the presence of this acid in the active site.
Lung cancer is the most common malignancy in the United States and is ranked second only to bladder cancer in the proportion of cases thought to be due to occupational exposures. We review the epidemiology of occupational lung cancer, focusing on agents identified as pulmonary carcinogens by the International Agency for Research on Cancer. We derive estimates of overall relative risks from the major studies of these lung carcinogens, and we also provide estimates of the number of exposed workers. Using our data as well as estimates from other authors, we estimate that approximately 9,000-10,000 men and 900-1,900 women develop lung cancer annually in the United States due to past exposure to occupational carcinogens. More than half of these lung cancers are due to asbestos. This estimate is likely conservative, in that we have restricted our analysis to confirmed lung carcinogens and have ignored occupations with documented excess risk but for which the specific agents are unknown. Also, our estimate of the proportion of workers exposed in the past is probably too low. Our estimate should be viewed only as broad approximation. Nevertheless, it is in line with other estimates by authors using different methods. The current number of cases estimated to be due to occupational exposure reflects past high exposures and is likely to drop in the future, unless other occupational lung carcinogens are confirmed or new carcinogens are introduced into the workplace.
A previous study has shown that acrylonitrile (ACN) has a long half-life in rainbow trout muscle and that [14C]ACN appears to be bound to a 10,000-Da protein in muscle. The labeled protein was purified from muscle of trout exposed to [14C]ACN, separated on 20% SDS-PAGE, and digested for amino acid analysis and sequence analysis. These studies indicated that the labeled protein was the Ca(2+)-binding protein parvalbumin. Parvalbumin is an important calcium-binding protein thought to be involved in the regulation of calcium levels in various parts of the body ranging from neurons to fast-twitch muscle contractions. To study the reaction between parvalbumin and [14C]ACN, frog parvalbumin was incubated with [14C]ACN in vitro under various conditions. These studies indicated that the maximum labeling occurred at 1 nmol/nmol parvalbumin and at pH 7. Amino acid analysis of the labeled protein indicated that the labeled amino acid was probably histidine, and endoproteinase Glu-C (V-8) digestion studies revealed that the 14C was in the 1-81 amino acid segment of the protein, an area that contains two histidines.