PubMed Health⌕ Search

Biomedical subjects

J Edmond

Publications and source records attributed to J Edmond.

At least 55 records · Page 3Linked to original sources
PubMed1984

Growth and development of rats artificially reared on different milk-substitutes.

Rat pups were artificially reared (AR) from postnatal day 4 or 5 till day 20 or 21, by fitting them with gastric cannulas through which milk-substitutes could be infused automatically. Three milk-substitutes were compared: milk M, the usual diet for AR studies, which was somewhat low in protein and very high in carbohydrate; milk A, which resembled rats' milk much more closely in composition; and milk isoM, which was based on the high-energy milk M but was made isoenergetic with milk A. Pups given these diets were termed ARM, ARA and ARisoM respectively. Siblings of the AR rats were left with their mothers to form a mother-reared (MR) control group. Rats were autopsied at 20 or 21 d. Growth in body-weight of all groups of AR pups lagged behind that of their MR siblings for about the first week of AR, but the ARM group showed complete catch-up and the ARA group partial catch-up in body-weight during the second week. ARisoM rats were growth-retarded throughout. Inspection of organ weights expressed relative to body-weight revealed disturbances of organ growth in all AR groups compared with MR animals. ARM rats showed excessive epididymal fat pad and liver weights, but deficits in gastrocnemius muscle, heart and adrenal weights. In contrast, ARA rats usually displayed increased spleen and stomach weights, but lower weight of interscapsular brown adipose tissue. ARisoM rats had high brain, liver and stomach weights and low muscle and spleen weights relative to body-weight. All AR groups had elongated small intestines. Hence the patterns of abnormal organ growth differed between groups. Those shown by the ARM and ARisoM groups seemed the more seriously abnormal. The diet approximating the composition of rats' milk (milk A) appears, as intended, to be an improved milk-substitute.

Animal Nutritional Physiological Phenomena↗
PubMed1983

Acetoacetate: a major substrate for the synthesis of cholesterol and fatty acids by isolated rat hepatocytes.

Evidence is presented that isolated, intact rat hepatocytes can synthesize fatty acids and cholesterol from acetoacetate. The quantitative importance of these processes is evaluated by measuring total rates of fatty acid and cholesterol synthesis by incorporation of 3H from 3H2O. The contribution of acetoacetate varies from 14-54% and from 21-75% for de novo synthesized fatty acids and cholesterol, respectively, depending on the physiological condition of the donor rat. The relative contribution of acetoacetate to cholesterol synthesis is 1.4-2.3-times greater than to fatty acid synthesis.

Acetoacetates↗
PubMed1982

Lipogenesis from ketone bodies in the isolated perfused rat liver. Evidence for the cytosolic activation of acetoacetate.

The production of ketone bodies by the isolated perfused rat liver has been measured by the dilution of the specific activity of tracer amounts of beta-hydroxy[3-14C]butyrate and by accumulation in the perfusate. The latter method has been found to underestimate ketogenesis by 12 to 44% because it does not take into account acetoacetate utilization by the liver. Incorporation of ketone bodies into fatty acids and 3-beta-hydroxysterols was compared to total lipid synthesis measured by incorporation of tritium from tritiated water. A preferential labeling of 3-beta-hydroxysterols over fatty acids was observed, which is consistent with the activation of acetoacetate in the cytosol by acetoacetyl-CoA synthetase. Ketone bodies contribute 19 to 80% of the carbon incorporated into sterols and up to 22% of the carbon incorporated into fatty acids, depending upon the metabolic status of the liver. The activity of acetoacetyl-CoA synthetase is more than sufficient to account for the rate of ketone body utilization. Conditions that decrease the citrate cleavage pathway of acetyl group translocation through the mitochondrial membrane are associated with an increase in carbon flux through acetoacetyl-CoA synthetase. Formation of acetoacetate in the mitochondria and its utilization in the cytosol thus appear to be a secondary pathway of acetyl group translocation operating concurrently with the predominant citrate cleavage pathway.

Acetoacetates↗
PubMed1982

Metabolism in the artificially reared rat pup: effect of an atypical rat milk substitute.

A substitute for rat milk [Messer et al., 1969 (1)] has been evaluated as a nutrient source to artificially feed rat pups from 4 days after birth. The rat milk substitute has a normal fat concentration, suboptimal protein concentration and a high carbohydrate concentration when compared to natural rat milk. Rat pups artificially reared on the mild substitute by intermittent infusion via miniaturized intragastric cannulae have: 1) atypical ketone body metabolism: lower than normal concentration and turnover of D-(--)-3-hydroxybutyrate in blood and less than normal amounts of D-(--)-3-hydroxybutyrate used for respiration, 2) atypical carbohydrate metabolism: higher than normal insulin and galactose concentrations in blood and a greater than normal amount of glucose used for respiration, and 3) atypical amino acid levels: the concentrations of several amino acids in blood were 60% or less than normal, and the concentration of taurine in plasma was negligible. We observed frequent head tremors, hyperreactivity to handling and about a 20% incidence of cataracts in rat pups reared on the milk substitute. We conclude this rat milk substitute is not suitable as a nutrient source for the developing rat pup.

Amino Acids↗
PubMed1979

Evidence for rate-limiting steps in sterol synthesis beyond 3-hydroxy-3-methylglutaryl-coenzyme A reductase in human leukocytes.

When human blood leukocytes are incubated with [2-14C]acetate only about 32% of the nonsaponifiable lipid radioactivity is recovered in digitonin-precipitable material. Using thin-layer chromatography and gas-liquid radiochromatography, we have determined that most of the label from [2-14C]acetate in the nonsaponifiable fractions is in lanosterol, squalene and an unidentified sterol. Only 11% of the acetate radioactivity is contained in cholesterol. This distribution does not change when cholesterol synthesis is depressed by the addition of lipoproteins to the medium. These findings are in marked contrast to studies with liver, where most of the nonsaponifiable radioactivity derived from acetate is recovered in digitonin-precipitable sterols. Furthermore, they suggest that rate-limiting steps beyond the 3-hydroxy-3-methylglutaryl coenzyme A reductase reaction exist in the sterol synthesis pathway of human leukocytes.

Acetates↗
PubMed1979

Determination of mevalonate in blood plasma in man and rat. Mevalonate "tolerance" tests in man.

A method is described for the determination of mevalonate in ultrafiltrates of blood plasma. The method depends on the phosphorylation of mevalonate with [gamma-32P]ATP and mevalonate kinase to 5-[32P]phosphomevalonate, and the subsequent isolation of the 5-[32P]phosphomevalonate together with known amounts of added 5-phospho[14C]mevalonate by ion-exchange chromatography. The 32P/14C ratio in the isolated 5-phosphomevalonate is a linear function of the mevalonate content of the samples. The smallest amount that can be determined is 1--2 pmol. The fasting level in human plasma varied between 20 and 75 pmol/ml. Human red blood cells absorb mevalonate from plasma relatively slowly; their maximum storage capacity is about 1.3 pmol/10(6) red cells. An oral and intravenous "mevalonate tolerance test" in man is described that can be carried out with 200 and 30 mumol. respectively, of the unlabeled (RS)-mevalonate in a 70-kg man. Beer and wine contain mevalonate at a concentration of 3--8 microns, too low to provide a significant amount of mevalonate even for heavy drinkers. The mevalonate content of the plasma from the blood of the vena cava inferior of male rats varied between 81 and 502 pmol/ml and is positively related to the levels of liver 3-hydroxy-3-methylgultaryl-CoA reductase, suggesting that the liver is probably the main source of mevalonate circulating in blood. The plasma of renal venous blood contained only 33--85% as much mevalonate as the arterial plasma.

Animals↗
PubMed1977

Control of 3-hydroxy-3-methylglutaryl coenzyme A reductase by endogenously synthesized sterols in vitro and in vivo.

Isolated rat hepatocytes converted mevalonolactone into sterol intermediates and fatty acids 6- to 8-fold faster than mevalonate salt at concentrations less than 6 X 10(-4) M. Incubation of hepatocytes for 3 h normally results in induction of 3-hydroxy-3-methylglutaryl-CoA reductase. This increase in enzyme activity was inhibited by mevalonolactone and by mevalonate salt; at each concentration between 6 X 10(-4) M and 6 X 10(-8) M the lactone was a more effective inhibitor than the salt. The increase in enzyme activity was completely prevented by 6 X 10(-4) M lactone, and at this concentration the cells synthesized from the lactone an amount of sterol per hour which approximated that leavingthe cells in the same period. Administration of mevalonolactone to intact rats resulted in a dose-dependent inhibition of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity. At the highest dose (400 mg of (RS)-mevalonolactone/200 g of rat) enzyme activities declined 85% within 45 min and were still suppressed below normals after 28 h. Mevalonolactone treatment resulted in increases in liver cholesterol content and in the cholesterol ester concentration of liver microsomes. The results demonstrate that the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase can be controlled by the rate of endogenous sterol synthesis both in vitro and in vivo.

Alcohol Oxidoreductases↗
PubMed1976

Mevalonate metabolism: role of kidneys.

More than one-half of the amount of mevalonate that is metabolized by pathways not leading to sterols is accounted for by the action of the kidneys. Conversion of mevalonate in vivo to squalene and sterols in the kidneys is confined almost entirely to the proximal and distal convoluted tubules in the cortex. More sterol than squalene is synthesized from mevalonate not only in the liver but also in the kidney.

Animals↗
PubMed1975

Abnormal induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase in leukocytes from subjects with heterozygous familial hypercholesterolemia.

Human leukocytes isolated from fresh defibinated blood were shown to utilize acetate and mevalonate for sterol synthesis. The capacity of the leukocytes to synthesize sterols is limited severely as compared to their ability to convert mevalonate into farnesyl pyrophosphate (which they hydrolyze rapidly to free farnesol) and into squalene. When leukocytes are incubated in a medium containing lipid-free serum, synthesis of sterols from acetate, but not from mevalonate, is much enhanced. It was shown that this increased synthesis resulted from increased levels of 3-hydroxy-3-methylglutaryl-CoA reductase activity in the cells. A comparison was made of the activation of sterol synthesis from acetate in leukocytes of normal individuals and of heterozygous familial hypercholesterolemics. The latter group responded to incubation in lipid-free sera with a significantly higher activation than the cells of normocholesterolemics. This activation was shown to be well correlated with a higher induction of 3-hydroxy-3-methylglutaryl-CoA reductase in the heterozygous cells than in the normals. The leukocytes of a heterozygous familial hypercholesterolemic individual were found to release, into a lipid-free incubation medium, more endogenously synthesized [3H]sterol (but not [3H]squalene) than the cells of a normal person. It is suggested that the genetic abnormality in heterozygous familial hypercholesterolemia could be accounted for by a mutation resulting in a weaker binding of a sterol repressor by heterozygous cells than by normal cells.

Acetates↗
PubMed1975

Metabolism of mevalonate in rats and man not leading to sterols.

C-5 of mevalonate appears as C0-2 in the breath of rats and men almost immediately after administration either by injection or by mouth. Adult rats exhaled up to 6.5% of a dose of RS-[5-14C]mevalonate (13% of the utilizable R-enantiomer) in the breath in 100 min. The 14-C02 was not derived either from the matabolism of cholesterol biosynthesized from [5-14C]mevalonate or from the metabolism of the unnatural S-enantiomer of mevalonate. The amount of 14-C02 expired in the breath was the same whether the [5-14C]mevalonate was given intravenously or in a drink of water to man. One normocholesterolemic man dissipated 12%, a mildly non-familial hypercholesterolemic man dissipated 10%, and a familial hypercholesterolemic man dissipated 7% of a dose of [5-14C]mevalonate in 24 hours (calculated as a per cent of the R-enantiomer). The observations support the hypothesis of the existence of a metabolic shunt of intermediates of sterol biosynthesis, derived from mevalonate, not leading to sterols.

Adult↗