Cholesterol metabolism in copper deficient rats.
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Biomedical subjects
Publications and source records attributed to K G Allen.
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The association of copper with cardiovascular disease and a possible involvement of copper in the metabolism of cholesterol prompted the study on hypercholesterolemia mediated by copper deficiency. Copper deficient rats were found to exhibit a highly significant cholesterolemia (P less than 0.001), and plasma cholesterol showed a significant correlation with hepatic copper concentration (P less than 0.03). Two copper deficient rats died with hemothorax. The hearts of copper deficient rats were hypertrophied with large areas of hemorrhage, inflammation and focal necrosis. Prominent subendocardial fibroplasia was evident in copper deficient animals. The myocardial arteries of copper deficient rats were normal, however, aortas showed large areas of distorted and depleted elastic fibers. The results are discussed in terms of a possible role for copper in cholesterol metabolism, and in the pathogenesis of atherosclerosis.
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The 15 exposed carboxyl groups of alpha-chymotrypsin were modified with glycine ethyl ester at low pH using barbodiimide reagent. The specificity of the modified enzyme (Chy-15) was studied over the pH range of 4 to 9 with both N-acylated and non-N-acylated amino acid esters. The modified enzyme had lower reactivity toward N-acylated esters than non-N-acylated esters compared to the native enzyme. Typical substances such as acetyl- and benzoyl-L-tyrosine ethyl esters retained 4 and 9% activity, whereas phenylalanine ethyl ester was slightly more reactive with the modified than with the native enzyme. The pH-rate profiles of acetyl-L-phenylalanine ethyl ester and tryptophan ethyl and benzyl esters were investigated in detail. Analysis of these profiles revealed three pKa values of approximately 5, 7, and 9 related to a functional carboxyl, imidazoyl, and an amino group, respectively. Since similar pKa values occur for the native enzyme, modification did not block the carboxyl corresponding to pKa 5. A mechanism is proposed for catalysis which includes both the protonated and unprotonated form of the imidazoyl (His-57) and utilizes water rather than a carboxyl (Asp-102) as the proton sink.
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A 57-year-old man received a cardiac allograft for severe ischemic heart disease. His endomyocardial biopsy at eight weeks postoperatively showed a focus of unusual myocardial morphology characterized by small diameter myocytes associated with loose, myxoid appearing stroma and a myocytic mitotic figure. We feel this may represent a unique type of myocardial repair.
The effects of modifying membrane fatty acid composition on cell growth, phospholipase C (PLC) and protein kinase C (PKC) activities, and prostaglandin E2 (PGE2) secretion were investigated. Hormone responsive MCF-7 human breast cancer cells were incubated in a serum-free medium containing epidermal growth factor and supplemented with physiologic concentrations (0.18-1.78 x 10(-5) M) of linoleic acid (LA) or conjugated linoleic acid (CLA). Linoleic acid stimulated cancer cell growth, while CLA was inhibitory. Supplementation with LA or CLA altered cell membrane composition. Linoleic acid stimulated PLC activity with or without GTP gamma (S), and tended to increase membrane PKC activity. However, CLA supplementation did not modify membrane PLC or PKC activity. Prostaglandin E2 secretion was not influenced by LA or CLA. These data show that growth inhibition by CLA was not mediated through PLC-, PKC- or PGE2-dependent signal transduction pathways, suggesting that another inhibitory mechanism may be involved. Although biological differences appeared to be modest (5-20% of control), the fact that LA and CLA treatment resulted in significant biological effects at physiologic concentrations is relevant, since most human cancers require years to develop.
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