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Biomedical subjects

K K Carroll

Publications and source records attributed to K K Carroll.

At least 91 records · Page 5Linked to original sources
PubMed1983

Distribution and metabolism of dolichol and dolichyl phosphate in rat liver.

The dolichol and dolichyl phosphate (Dol-P) content of various tissues and liver subcellular fractions obtained from rats have been measured directly using high pressure liquid chromatographic methods developed in this laboratory. Spleen contained the highest concentration of dolichol, while other tissues including serum had smaller amounts. Although considerable differences in homologue distribution patterns were observed among the tissues examined, a number of purified subcellular fractions obtained from liver (nuclei, mitochondria, cytosol, and microsomes) exhibited a single common pattern. Only some 5% of liver dolichol appeared in the microsomal compartment of the cell where glycoprotein formation occurs, while 50% of the dolichol in this tissue was found in a lysosome-enriched fraction. The concentrations of dolichol present in liver nuclei, mitochondria, whole microsomes (also rough and smooth, endoplasmic recticulum (RER and SER, respectively), and cytosol were considerably lower (on a protein basis) than those present in whole liver. Besides the lysosome-enriched fraction, only plasma membranes and Golgi contained dolichol at concentrations equal to or greater than those present in liver homogenates. The low concentrations of dolichol found in microsomes suggest that the amounts of dolichol available for Dol-P formation via the CTP-dependent kinase reaction may be rate limiting. Most of the Dol-P in liver could be recovered in the microsomal fraction. Dol-P accounted for 4 and 40% of the sum of alcohol + dolichyl fatty acyl ester + Dol-P forms present in whole liver and in microsomes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

The subcellular localization of enzymes of dolichol metabolism in rat liver.

Dolichyl phosphate is an intermediate in the glycosylation of N-glycosamidic linked glycoproteins in mammalian systems, and its availability may be a limiting factor in glycoprotein biosynthesis. The basic kinetics and subcellular distribution of enzymes which may influence the concentration of dolichyl phosphate in rat liver have therefore been investigated. These include dolichyl phosphate phosphatase, dolichol phosphokinase, dolichyl fatty acyl ester synthetase, GDP-mannose dolichyl phosphate mannosyl transferase, and UDP-glucose dolichyl phosphate glucosyl transferase. The specific activity of the enzymes was highest in the microsomes, except for dolichyl phosphate phosphatase and dolichyl fatty acyl ester synthetase, which were most concentrated in the plasma membrane and the cytosol fraction, respectively. The nuclei contained all of the enzyme activities while the mitochondria and cytoplasm were generally less active. The presence of both dolichol phosphokinase and dolichyl phosphate phosphatase in microsomes and nuclei, which contain the highest glycosyl transferase activities, may provide a means for direct enzymatic control of levels of dolichyl phosphate.

Acyltransferases↗
PubMed1982

Inhibitory effect of a fat-free diet on mammary carcinogenesis in rats.

Young female Sprague-Dawley rats were administered 7,12-dimethylbenz(a)anthracene, and a week later the rats were transferred from commercial feed to a semipurified diet containing 20% corn oil. Eight weeks after receiving the carcinogen, half of the rats were changed to a fat-free diet to determine the effects on mammary tumor growth and development. After another 20 weeks, rats fed the fat-free diet had significantly fewer tumors per tumor-bearing rat and the tumors were smaller than those of rats that continued on the high-fat diet. Rats fed the fat-free diet weighed somewhat less, but showed no physical evidence of essential fatty acid deficiency. Tumors regressed in about half of the rats on the fat-free diet and in some cases became nonpalpable. After 28 weeks on this diet, the remaining rats were transferred back to the high-fat diet and subsequently showed a marked stimulation in tumor growth and development. This continued even after the rats were returned to the fat-free diet 8 weeks later, indicating that the tumors were no longer susceptible to the deprivation of dietary fat. The results of this study provide further evidence that dietary fat affects the promotional stage of mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

The submicrosomal distribution of dolichol and dolichol phosphokinase activity in rat liver.

Microsomes were isolated from rat liver and fractionated into Golgi, smooth endoplasmic reticulum (SER), and rough endoplasmic reticulum (RER) components, and the purity of these fractions was determined. The dolichol contents of each of the three fractions was estimated, using high-pressure liquid chromatography. Although highest concentrations (1940 ng/mg protein) were found in Golgi, the RER contained the largest absolute amounts. The presence of large quantities of dolichol in RER is consistent with the role of dolichol as an intermediate in asparagine-linked glycoprotein synthesis. RER and SER fractions contained high specific activities for dolichol phosphokinase, while the activity in Golgi was quite low. High concentrations of dolichol in Golgi and high dolichol phosphokinase activity in SER suggest that dolichol (and dolichyl phosphate) may be utilized in Golgi for glycoprotein processing and in the transmembrane movement of sugars such as galactose.

Animals↗
PubMed1982

Hypercholesterolemia and atherosclerosis: effects of dietary protein.

Hypercholesterolemia and atherosclerosis can be produced in rabbits by feeding cholesterol-free, semipurified diets containing proteins derived from animal sources, but these effects have not been observed with similar diets in which the protein is derived from plants. This difference appears to be largely caused by differences in amino acid composition of the dietary proteins. Epidemiologic data on human populations show a strong positive correlation between dietary animal proteins and mortality from cardiovascular disease. It has also been found that the level of plasma cholesterol in human subjects can be reduced significantly by substituting soybean protein for animal protein in the diet. Studies of the mechanism of action of dietary protein have shown that rabbits fed casein have a slower turnover of plasma cholesterol, excrete less neutral steroids and bile acids, and absorb cholesterol from the intestine more readily than rabbits fed soy protein in cholesterol-free, semipurified diets. The excess cholesterol in the plasma of casein-fed rabbits is carried mainly in the very low-density and intermediate-density lipoproteins. These lipoproteins also contain increased amounts of apoproteins corresponding to apo E and apo C, show differences in turnover rates compared to the corresponding lipoproteins from rabbits fed soy protein.

Amino Acids↗
PubMed1981

Influence of diet on mammary cancer.

Analysis of epidemiological data and experiments with animals have provided evidence that dietary fat has an important influence on mammary cancer. Further epidemiological studies should be carried out to examine this relationship more fully, and additional experimental work is required to determine the mechanisms by which dietary fat influences mammary cancer in animals. Dietary carbohydrate and minor dietary components, such as retinoids and certain trace elements, have also been shown to influence mammary cancer in animals. Decreasing the fat content of the diet may offer a practical means of reducing mortality from breast cancer, which continues to be a major cause of death in many parts of the world.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Polyunsaturated fatty acids as promoters of mammary carcinogenesis induced in Sprague-Dawley rats by 7,12-dimethylbenz[a]anthracene.

The development of mammary tumors was examined in female noninbred Sprague-Dawley rats fed either a low-fat diet or high-fat diets containing different fats and fatty acid esters. Each rat was given 5 mg 7,12-dimethylbenz[a]anthracene by stomach tube 1 week before diets were introduced. Addition of 3% ethyl oleate (an ethyl ester of an unsaturated fatty acid) to a diet high in saturated fat (coconut oil) had no significant effect on tumor development, but the addition of 3% ethyl linoleate (an ethyl ester of a polyunsaturated fatty acid) increased the tumor yield to about twice that in rats fed either the high-saturated fat diet or a low-fat diet. Animals fed the high-saturated fat diet containing 3% ethyl linoleate developed as many tumors as those fed a 20% sunflower seed oil diet, though the sunflower seed oil diet contained about four times as much linoleate. Rats fed a high coconut oil diet containing 3% menhaden fish oil, which contains polyunsaturated fatty acids of the linolenate family (but having little linoleic acid), also developed as many tumors as those fed the 20% sunflower seed oil diet. These differences in mammary tumor yield could not be explained by alterations in the serum levels of prolactin, estrogen, or progesterone. However, the higher tumor yields were associated with increased unsaturation of mammary tissue phospholipids.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Neutral fats and cancer.

High-fat diets enhance the development of mammary and intestinal tumors on animals, and dietary fat also shows a strong positive correlation with mortality from cancers of the breast and colon in human populations. In animals, dietary fat appears to act as a promoter of carcinogenesis rather than as an influence in the initiation of tumors. Polyunsaturated fats enhance mammary tumorigenesis and stimulate tumor growth more effectively than do saturated fats. However, diets containing a small amount of polyunsaturated fat and a high level of saturated fat increase mammary tumor yields as effectively as do diets containing a high level of polyunsaturated fat. Fatty acids of either the linoleate or linolenate family appear to be able to satisfy the small requirement for polyunsaturated fat. The mechanism by which dietary fat influences mammary tumorigenesis is not known but may involve hormonal effects, immune responses, to alterations in cellular membranes. Dietary fat is thought to enhance the development of intestinal tumors by stimulating production of bile acids, some of which act as promoters of tumorigenesis.

Breast Neoplasms↗
PubMed1981

Dietary promotion of carcinogenesis.

Environmental influences are thought to be largely responsible for the marked geographical differences in cancer mortality observed in epidemiological studies. Diet has been implicated as a significant environmental variable because certain dietary constituents, such as fat, show a positive correlation with mortality from cancer at specific sites such as breast and colon. Similar correlations have been observed in experiments with animal models. The studies with animals have also provided evidence that the dietary effects are exerted mainly at the promotional stage of carcinogenesis. Since breast and colon cancers account for a large proportion of cancer deaths in many countries, tumor-promoting effects of diet may be an important factor in overall cancer mortality.

Animals↗
PubMed1980

Analysis of dolichol in human tissues by high pressure liquid chromatography.

Dolichol from human liver was shown by reverse-phase high pressure liquid chromatography to consist of a series of homologues ranging in length from 17 to 23 isoprene units. The two major components, corresponding to 19 and 20 isoprene units, respectively, were isolated and identified by mass spectrometry. Dolichyl palmitate, synthesized from liver dolichol, showed an identical series of peaks with longer retention times. Attempts to chromatography dolichyl phosphate under similar conditions were unsuccessful. Dolichol from uterine tissue and several other human tissues showed a shift toward shorter chain length, with a predominance of homologues containing 18 and 19 isoprene units.

Chromatography, High Pressure Liquid↗
PubMed1980

Effects of dietary proteins and amino acid mixtures on plasma cholesterol levels in rabbits.

Amino acid mixtures corresponding to either casein or egg yolk protein when fed to rabits ina low fat, cholesterol-free semipurified diet, produced the same degree of hypercholesterolemia as the proteins themselves. Amino acid mixtures corresponding to soy protein isolate or sunflower protein gave low plasma cholesterol levels, but not as low as those obtained with the intact proteins. Experiments were designed to identify amino acids responsible for the differential in plasma cholesterol produced by casein or soy protein amino acid mixtures. Plasma cholesterol levels obtained with a casein amino acid mixture containing half the amounts of essential amino acids were significantly higher than he corresponding soy protein mixture. Feeding trials based on systematic modifications to the casein and soy protein mixtures indicated that interaction between essential and non-essential amino acids was important in determining plasma cholesterol levels. In further experiments, protein components were formulated by adding amino acids to casein to give a mixture corresponding to soy proteins, or by adding amino acids to soy protein, or by adding amino acids to soy protein to give a mixture equivalent to casein. These diets failed to reverse plasma cholesterol levels which suggests differences in digestion and absorption of proteins relative to amino acid mixtures.

Amino Acids↗
PubMed1980

Properties of a dolichol phosphokinase activity associated with rat liver microsomes.

Rat liver microsomes show a capacity to synthesize [1-3H]dolichyl phosphate from [1-3H]-dolichol. Formation of [1-3H]dolichyl phosphate increased continuously over 15 min although the reaction rate was never completely linear. Product formation was directly proportional to microsomal protein concentration between 1.1 mg/mL and the highest concentration tested, 5.5 mg/mL. The reaction rate was linear with respect to the dolichol content of the assay mixture to a saturation point (120 microM). An apparent Km of 50 microM was established for dolichol. The normal phosphate donor for the reaction is CTP and not ATP. The optimum concentration of CTP was 10 mM, and an apparent Km of 4 mM was calculated for this nucleoside triphosphate. The reaction was totally dependent on divalent metal ion, magnesium being more effective than calcium. The optimum concentration of magnesium ion and CTP were the same (10 mM), suggesting that MgCTP2- is utilized as the normal enzyme substrate. Activity measured in the absence of Triton X-100 was only 5% of the activity observed at the optimum (0.5% w/v) detergent concentration. The measurable levels of dolichol phosphokinase could be doubled by the inclusion of 10-15 mM NaF as phosphatase inhibitor. Optimal enzymatic activity was obtained between pH 7.0 and pH 7.5 and could be inhibited by EDTA. The sulfhydryl reagent DTT was slightly stimulatory while the product of the reaction, dolichyl phosphate, was noninhibitory at the highest concentration tested (13.8 microM). The second reaction product (CDP) inhibits the enzymatic phosphorylation of dolichol.

Animals↗