Metabolic studies on scorbutic guinea pigs. iv. fatty acid metabolism in vitro.
TL;DR: Thein vitro oxidation of terminally labeled higher fatty acids like lauric, myristic and stearic to 14CO2 by the mitochondrial tissue preparation from scorbutic guinea pigs was appreciably depressed as a result of this disease and ATP and Mg++ could fortify considerably this defect.
Abstract: 1.
The tissue weight and fatty acid concentration were observed to be higher in the case of scorbutic guinea pigs compared to the pair-fed control animals. Amongst the tissues analysed, maximum increase in fatty acid level was found with the liver tissue.
2.
Fatty acid synthesis by the scorbutic tissuein vitro was diminished. Both tissue homogenates and slices had less capacity to convert acetate-1-14C to labeled fatty acids. The specific activities of the synthesised fatty acids by tissues of scorbutic guinea pigs were appreciably less than that synthesised by the corresponding tissue preparations from the pairfed animals. Incorporation by tissue from normal animal fed ‘ad libitum’ was more compared to the tissue from pair-fed one.
3.
Hepatic oxidation of acetate-1-14C to14CO2 by slices was depressed in scurvy.
4.
Mitochondria prepared from scorbutic liver tissue exhibited a lower oxidation of octanoate-1-14C to14CO2. Addition of essential cofactors like ATP and Mg++ in the system did not improve the depressed oxidation.
5.
Thein vitro oxidation of terminally labeled higher fatty acids like lauric, myristic and stearic to 14CO2 by the mitochondrial tissue preparation from scorbutic guinea pigs was appreciably depressed as a result of this disease. ATP and Mg++ could fortify considerably this defect.
6.
The significance of these findings in relation to lipid metabolism in scurvy is discussed.
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TL;DR: It is suggested that ascorbate affects the synthesis or breakdown of the 7alpha-hydroxylating system, in particular the cytochrome P-450 component.
Abstract: Cholesterol 7alpha-hydroxylase activity was assayed in liver microsomes from guinea pigs supplemented with ascorbate and from guinea pigs in a state of ascorbate deficiency. A mass fragmentographic method was used by which the 7alpha-hydroxylation of endogenous cholesterol could be measured. The 7alpha-hydroxylation was markedly reduced in the ascorbate-deficient animals as compared to animals treated with ascorbate. Addition of ascorbate to the incubations did not increase this activity. 11- and 12-Hydroxylation of laurate as well as 25- and 26-hydroxylation of 5beta-cholestane-3alpha, 7alpha-diol were not significantly affected by the ascorbate status of animals. In the presence of excess NADPH-cytochrome P-450 reductase and a phospholipid, partially purified cytochrome P-450 from the microsomal fraction of liver of an ascorbate-deficient guinea pig had a much lower capacity to 7alpha-hydroxylate [4-14C]cholesterol than a corresponding system containing cytochrome P-450 from liver of an ascorbate-supplemented guinea pig. It is suggested that ascorbate affects the synthesis or breakdown of the 7alpha-hydroxylating system, in particular the cytochrome P-450 component.
114 citations
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TL;DR: The aim of the experiments reported here was to determine whether an increased cholesterol accumulation in the tissues of guinea pigs with an ascorbic acid deficiency is caused by retarded cholesterol catabolism.
Abstract: There is much disagreement regarding the effects of acute ascorbic acid deficiency on cholesterol metabolism in the guinea pig (1-6). The contradictions in results may be explained to a certain extent by the dynamic character of avitaminosis C development, during which the character of metabolic disturbances is changed according to development of scurvy. When following the dynamics of the changes in adrenal cholesterol levels during development of avitaminosis C in guinea pigs, we have found (7) that distinct cholesterol accumulation can be observed at the beginning. During further stages, the cholesterol level reached its normal value and only in the last stage of scurvy, which was accompanied by a decrease in body weight, did the cholesterol concentration in adrenals decrease to below control values. Results attained in animals with acute scurvy may be, however, affected by secondary nonspecific effects, such as food refusal followed by a sudden drop in body weight, hemorrhaging, total metabolic disorganization, et cetera. Some of these changes (e.g., hemorrhage) cannot be simulated by pair-feeding. Moreover, acute experimental scurvy does not reproduce the latent ascorbic acid deficiency observed in humans. The aim of our experiments was to approach the contemporary state in human nutrition and to use a metabolically better defined state than acute scurvy. All these reasons have led us to elaborate a model of chronic hypovitaminosis C in guinea pigs (8). When using this model, we have found that in male guinea pigs with chronic ascorbic acid deficiency a significant accumulation of cholesterol occurs in the liver (9, 10). When guinea pigs were fed an atherogenic diet supplemented with 0.3% cholesterol, the effect of ascorbic acid deficiency was reflected in an increased accumulation of cholesterol in a number of other tissues, including the aorta wall (1 1). A significant negative correlation was confirmed as existing between the tissue cholesterol concentration and saturation of tissues with ascorbic acid, i.e., with decreasing saturation of tissues with the vitamin, the cholesterol accumulation in the relevant tissue was increasing (12). The increased cholesterol accumulation in the tissues of hypovitaminotic guinea pigs can be explained neither by increased synthesis of endogenous cholesterol from acetate-1-14C (7, 13) nor by increased absorption of exogenous cholesterol (14). Speed of these processes is either unchanged or even decreased in guinea pigs with hypovitaminosis C. The aim of the experiments reported here was to determine whether an increased cholesterol accumulation in the tissues of guinea pigs with an ascorbic acid deficiency is caused by retarded cholesterol catabolism.
60 citations
Cites background from "Metabolic studies on scorbutic guin..."
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TL;DR: This chapter discusses marginal vitamin C deficiency, lipid metabolism, and atherogenes, which develops in the presence of relatively low plasma-cholesterol levels reminiscent of human hypercholesterolemia.
Abstract: Publisher Summary This chapter discusses marginal vitamin C deficiency, lipid metabolism, and atherogenes. Vitamin C holds a special position among the vitamins, because most vertebrates synthesize it in the glucuronic acid pathway of glucose metabolism and are, therefore, not dependent on a supply from external sources. Cholesterol atherosclerosis in guinea pigs, as distinct from rabbits, develops in the presence of relatively low plasma-cholesterol levels reminiscent of human hypercholesterolemia. There is also a parallel with the pathogenesis of human atherosclerosis in the slow development of atherosclerotic lesions in guinea pigs. The lipoprotein metabolism of guinea pigs is very different from that of man because normal guinea pig plasma contains no detectable high-density lipoproteins and no lipoproteins with alpha mobility. Serum and tissue cholesterol concentrations are the outcome of a great number of processes mutually bound by feedback mechanisms, such as cholesterol distribution between blood and tissues, endogenous cholesterol synthesis, the absorption of exogenous cholesterol, cholesterol excretion, and the transformation of cholesterol to bile acids.
48 citations
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TL;DR: Etudes physiologiques chez l'homme et les primates de l'effet de la vitamine C, oxydation des lipoproteines and lipides, etudes epidemiologiques.
Abstract: There has been some inconsistency in data on the effect of vitamin C on human plasma cholesterol levels. The purpose of this review is to analyze the published intervention studies in order to identify the factors that may have caused conflicting results. It discusses cholesterol and triglyceride metabolism, physiological studies, intervention studies, epidemiological studies, and conclusions
45 citations
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TL;DR: Serum ascorbic acid level was independently associated with high-density lipoprotein cholesterol (HDL-C) among women and may be particularly important for women at increased risk for coronary heart disease, if the observed associations are linked causally.
Abstract: Objective: To examine the relation of serum ascorbic acid level to serum lipid and lipoprotein levels among a random sample of the US adult population.Methods: Using linear regression, the relation of serum ascorbic acid level to serum lipid and lipoprotein levels was examined among 5,412 women and 5,116 men enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), 1976–1980. Age, race, body mass index, level of physical activity, level of education, alcohol intake, and dietary energy, cholesterol, and fat intakes, and other potential confounders were included in the multivariate models.Results: Serum ascorbic acid level was independently associated with high-density lipoprotein cholesterol (HDL-C) among women; each 1 mg/dl increase in serum ascorbic acid level (range 0.1 to 2.7 mg/dl) was associated with a 2 mg/dl increase in HDL-C level (p=0.001). Because other investigators have demonstrated an inverse relation between ascorbic acid intake or blood levels and total serum chol...
26 citations
References
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132 citations
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TL;DR: The utilization of carboxyl and methyl-C4-acetic acid, /3-C14-pyruvic acid, and carboxyC4 -butyric, hexanoic, and octanoic acids for this biosynthesis of long chain fatty acids is concerned.
Abstract: The biological synthesis of long chain fatty acids from acetate by slices of rat liver tissue was demonstrated by Bloch, Borek, and Rittenberg (1) in 1946, and has been repeated by several investigators (2, 3). The effect of insulin on this incorporation was studied by Bloch and Kramer (2), who reported that, whereas insulin inhibited the incorporation of labeled acetate into fatty acids, the combination of insulin and non-labeled pyruvate resulted in an increased incorporation of the labeled acetate. It was of interest to determine whether other short chain fatty acids, as well as acetic acid, might be utilized by liver slices for the synthesis of higher fatty acids. This report isaccordingly concerned with the utilization of carboxyl and methyl-C4-acetic acid, /3-C14-pyruvic acid, and carboxylC4-butyric, hexanoic, and octanoic acids for this biosynthesis. The experiments reported here reveal some information concerning the mechanism by which these substrates are incorporated into fatty acids. A study of the effect of insulin upon this process has also been made.
115 citations