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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate of chain elongation of palmityl-CoA to stearyl-CoA in rat liver microsomes was studied in connection with the nutritional status of the rats. The microsomal chain elongation activity, which had been decreased by starvation for 48 hr, was rapidly increased to a high level on refeeding. The apparent Km value for malonyl-CoA in both normal and refed rats was the same, 1.2 X 10(4)M. Both cycloheximide and actinomycin D prevented the induction of microsomal chain elongation activity which was associated with refeeding. In addition, the activity of acyl-CoA hydrolase and the rates of esterification of acyl-CoA into phospholipids and neutral lipids in microsomes were not changed by the dietary alteration. These results support the conclusion that changes of the activity of microsomal chain elongation of palmityl-CoA in various nutritional status result from a rapid synthesis of new enzyme(s).
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PMID:Dietary control of the chain elongation of palmityl-CoA in rat liver microsomes. 86 44

1. Rates of ketogenesis from endogenous butyrate or oleate were measured in isolated hepatocytes prepared from fed rats during different reproductive states [virgin, pregnant, early-lactating (2-4 days) and peak-lactating (10-17 days)]. In the peak-lactation group there was a decrease (25%) in the rate of ketogenesis from butyrate, but there were no differences in the rates between the other groups. Wth oleate, the rate of ketogenesis was increased in the pregnant and in the early-lactation groups compared with the virgin group, whereas the rate was 50% lower in the peak-lactation group. 2. Experiments with [1-(14)C]oleate indicated that these differences in rates of ketogenesis were not due to alterations in the rate of oleate utilization, but to changes in the amount of oleoyl-CoA converted into ketone bodies. 3. Although the addition of carnitine increased the rates of ketogenesis from oleate in all groups of rats, it did not abolish the differences between the groups. 4. Measurements of the accumulation of glucose and lactate showed that hepatocytes from rats at peak lactation had a higher rate of glycolytic flux than did hepatocytes from the other groups. After starvation, the rate of ketogenesis from oleate was still lower in the peak-lactation group compared with the control group. This suggests that the alteration in ketogenic capacity in the former group is not merely due to a higher glycolytic flux. 5. It is concluded that livers from rats at peak lactation have a lower capacity to produce ketone bodies from long-chain fatty acids which is due to an alteration in the partitioning of long-chain acyl-CoA esters between the pathways of triacylglycerol synthesis and beta-oxidation. The physiological relevance of this finding is discussed.
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PMID:Effects of lactation of ketogenesis from oleate or butyrate in rat hepatocytes. 88 50

Higher omega-oxidation activities in the diabetic mammal and the starved one suggest that omega-oxidation mechanism plays an important role under these conditions. Dicarboxylic acid that is the final product of omega-oxidation can be metabolized further by beta-oxidation, subsequently, formation of succinyl-CoA and short-chain dicarboxylic acid might be increased in the liver. The physiological significance of omega-oxidation might consist in supplying the substrate of TCA cycle for utilization of acetyl-CoA and excreting the short-chain dicarboxylate in urine resulting in the decrease of ketone bodies in the blood, especially in diabetes and starvation. On the bases of these information, it is important to investigate the metabolism of dicarboxylic acids. Generally, fatty acids must be activated before they enter the metabolic pathway. By in vitro studies with rat liver homogenate, we have recently demonstrated that octadecaned-ioic acid must be activated by ATP-Mg2+ and CoA as monocarboxylic acid is. However, it has not been studied to compare the activity of acyl-CoA synthetase on mono and dicarboxylic acid. So, in this report, we assayed the activity of acyl-CoA synthetase in beef liver preparations using palmitic or hexadecanedioic acid (C1;16) as substrate. The results are as follows 1) Activation capacity of the supernatant of sonicated mitochondria was less than that of sonicated microsome for either palmitate or hexadecanedioate. 2) Activation capacity for hexadecanedioate was less than that for palmitate in both supernatant of sonicated mitochondria and that of sonicated microsome. 3) In our experiment, it might be suggested that the subcellular distribution of hexadecanedioate activation is almost identical with that of palmitate activation.
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PMID:[Acyl-CoA synthetase activity of long-chain mono and dicarboxylic acid in beef liver preparations (author's transl)]. 94 21

The stimulatory effect of starvation on omega oxidation of stearate by the 20,000 X g supernatant fluid of rat liver homogenates was studied. The effect was obtained after starvation for 24 hours. Starvation for longer times did not further increase omega oxidation. The stimulatory effect of starvation on omega oxidation of stearic acid was accompanied by a reduced incorporation of stearic acid into phosphatidic acid, diglycerides, and triglycerides. Substitution of the 100,000 X g supernatant fluid from liver homogenate of starved rats with 100,000 X g supernatant fluid from liver homogenates of control rats reduced the microsomal omega oxidation of stearic acid with a simultaneous increase in incorporation of stearic acid into the different glycerides. Under the latter conditions almost no free stearic acid could be isolated from the incubation mixture after the incubation. Of three different soluble factors necessary for glyceride formation, ATP appeared to be the most important from a regulatory point of view. Thus the soluble fraction of liver homogenate from a starved rat was shown to contain suboptimal concentrations of ATP. Addition of physiological amounts of ATP to the 20,000 X g supernatant fluid of homogenate of liver of starved rats had the same effect as addition of 100, 000 X g supernatant fluid from liver homogenate of control rats, i.e. decrease in omega oxidation and increase in formation of glycerides. Addition of sn-glycerol 3-phosphate and CoA-SH in amounts optimal for glyceride formation to the 20,000 X g supernatant fluid of liver homogenate of starved rats had only small effects on omega oxidation and glyceride formation. The results are consistent with a competition for free fatty acids between the acyl-CoA synthetases involved in biosynthesis of glycerides and the microsomal hydroxylase(s) involved in omega oxidation of fatty acids. The concentration of ATP in the soluble fraction is of importance in this competition. The possibility is discussed that this competition is of importance also under in vivo conditions and that a decreased rate of esterification in the starved state is responsible for the higher excretion of omega-oxidized fatty acids in urine in the ketotic state.
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PMID:On the mechanism of regulation of omega oxidation of fatty acids. 95 85

Fat cells isolated from rat epididymal adipose tissue were incubated with albumin-bound [14C]palmitate. Incorporation of 14C into 14CO2 and glycerides was measured. Some evidence is presented to suggest that the exogenous palmitate pool is in isotopic equilibrium with intracellular precursors for these metabolic processes. Precautions were taken to minimize dilution of the exogenous palmitate pool by fatty acids released from the cells. 14CO2 production from [1-14C]palmitate was 3 times that from [16-14C]palmitate. Octanoate increased this differential oxidation of palmitate carbons and also inhibited palmitate oxidation without similarly affecting esterification. Glucose increases palmitate esterification in cells from fed or starved rats. Insulin potentiated this effect of glucose. Glucose influenced palmitate oxidation in a more complex manner, dependent upon the glucose concentration. Both the observation that esterification constitutes 99% of the metabolic flux of fatty acid and the manner in which glucose, insulin, or starvation influence palmitate esterification and oxidation suggested that factors controlling esterification may alter oxidation as a secondary effect, but not vice versa. It is suggested that oxidation and esterification compete for a single intracellular precursor, possibly extramitochondrial long chain fatty acyl CoA.
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PMID:Factors affecting fatty acid oxidation in fat cells isolated from rat white adipose tissue. 96 42

The synthesis of ketone bodies by intact isolated rat-liver mitochondria has been studied at varying rates of acetyl-CoA production and of acetyl-CoA utilization in the Krebs cycle. Factors which enhanced the rate of acetyl-CoA production caused an increase in the fraction of acetyl-CoA which was incorporated into ketone bodies. On the other hand, it was found that factors which stimulated the formation of citrate lowered the relative rate of ketogenesis. It is concluded that acetyl-CoA is preferentially used for citrate synthesis, if the level of oxaloacetate in the mitochondrial matrix space is adequate. The intramitochondrial level of oxaloacetate, which is determined by the malate concentration and the ratio of NADH over NAD+, is the main factor controlling the rate of citrate synthesis. The ATP/ADP ratio per se does not affect the activity of citrate synthase in this in vitro system. Ketogenesis can be described as an overflow of acetyl-groups: Ketone-body formation is stimulated only when the rate of acetyl-CoA production increases beyond the capacity for citrate synthesis. The interaction between fatty acid oxidation and pyruvate metabolism and the effects of long-chain acyl-CoA on mitochondrial metabolism are discussed. Ketone bodies which were generated during the oxidation of [1-14C] fatty acids were preferentially labelled in their carboxyl group. This carboxyl group had the same specific activity as the acetyl-CoA pool, whereas the specific activity of the acetone moiety of acetoacetate was much lower, especially at low rates of ketone-body formation. The activities of acetoacetyl-CoA deacylase and the hydroxymethylglutaryl-CoA (HMG-CoA) pathway were compared in soluble and mitochondrial fractions of rat- and cow-liver in different ketotic states. In rat-liver mitochondria, both pathways of acetoacetate synthesis were stimulated upon starvation or in alloxan diabetes. In cow liver, only the HMG-CoA pathway was increased during ketosis in the mitochondrial as well as in the soluble fraction.
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PMID:Aspects of ketogenesis: control and mechanism of ketone-body formation in isolated rat-liver mitochondria. 119 5

Dicarboxylic acids are excreted in urine when fatty acid oxidation is increased (ketosis) or inhibited (defects in beta-oxidation) and in Reye's syndrome. omega-Hydroxylation and omega-oxidation of C6-C12 fatty acids were measured by mass spectrometry in rat liver microsomes and homogenates, and beta-oxidation of the dicarboxylic acids in liver homogenates and isolated mitochondria and peroxisomes. Medium-chain fatty acids formed large amounts of medium-chain dicarboxylic acids, which were easily beta-oxidized both in vitro and in vivo, in contrast to the long-chain C16-dicarboxylic acid, which was toxic to starved rats. Increment of fatty acid oxidation in rats by starvation or diabetes increased C6:C10 dicarboxylic acid ratio in rats fed medium-chain triacylglycerols, and increased short-chain dicarboxylic acid excretion in urine in rats fed medium-chain dicarboxylic acids. Valproate, which inhibits fatty acid oxidation and may induce Reye like syndromes, caused the pattern of C6-C10-dicarboxylic aciduria seen in beta-oxidation defects, but only in starved rats. It is suggested, that the origin of urinary short-chain dicarboxylic acids is omega-oxidized medium-chain fatty acids, which after peroxisomal beta-oxidation accumulate as C6-C8-dicarboxylic acids. C10-C12-dicarboxylic acids were also metabolized in the mitochondria, but did not accumulate as C6-C8-dicarboxylic acids, indicating that beta-oxidation was completed beyond the level of adipyl CoA.
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PMID:Formation and degradation of dicarboxylic acids in relation to alterations in fatty acid oxidation in rats. 154 29

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pantothenic acid in health and disease. 174 61

Low rates of triacylglycerol (TAG) biosynthesis were observed in cell-free extracts of Candida curvata, but rates were increased up to 10-fold by adding either alpha- or beta-cyclodextrins. Spheroplasts, whole or gently disrupted, had higher rates of incorporation of both [U-14C]glycerol 3-phosphate or [1-14C]oleate into triacylglycerol and the intermediates of its biosynthesis: lysophosphatic acid, phosphatidic acid and diacylglycerol. Fatty acyl-CoA synthetase was highest with palmitate, oleate and linoleate but was some 6- to 8-fold lower with stearate. Stearate and stearoyl-CoA were poorly incorporated into lipids. Subcellular fractionation of the spheroplasts into mitochondrial, microsomal, lipid bodies and supernatant fractions diminished the rates of 14C incorporation of oleate into triacylglycerol. By comparing the relative specific activities for each activity in each fraction, the fatty acyl-CoA synthetase activity appeared mainly in the lipid bodies, and that for phosphatidic acid formation was mainly in the mitochondrion; other activities were too weak and too dispersed for accurate assessment of their location. Recombining all the subcellular fractions restored triacylglycerol synthesizing activity. Omitting any single fraction from the mixture did not result in restoration of triacylglycerol synthesizing activity. Starvation of the yeast, which leads to utilization of the endogenous lipid reserves, stimulated fatty acyl-CoA synthetase activity, but diminished phosphatidic acid and triacylglycerol biosynthesis indicating probable induction of beta-oxidation in the peroxisomes and repression of lipid biosynthesis.
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PMID:Triacylglycerol synthesis in the oleaginous yeast Candida curvata D. 205 92

It has recently been reported that a precursor of p21ras (pro-p21ras) becomes modified by a metabolite of mevalonic acid prior to conversion to mature p21ras. We have examined the effect of blocking isoprenoid biosynthesis on this process. Fluoromevalonate, which inhibits the conversion of pyrophosphomevalonate to isopentenyl pyrophosphate, blocks the incorporation of radioactive mevalonate into pro-p21ras, demonstrating the mevalonate must be converted to an isoprenoid prior to such incorporation. Starvation of CHO-K1 cells for mevalonic acid by treatment with mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, or mevalonate deprivation in a mevalonate auxotroph defective in HMG-CoA synthase activity results in the accumulation of pro-p21ras. The precursor, accumulated due to either of these treatments, is converted through an intermediate form to the mature p21ras by incubation of cells with mevalonate. Incubation of cells with 25-hydroxycholesterol, the pleiotropic transcriptional down-regulator of cholesterol biosynthesis does not, however, result in the accumulation of pro-p21ras. This result indicates that in contrast to the regulation of cholesterol biosynthesis in mammalian cells, important regulatory control other than at the level of HMG-CoA reductase is involved in the isoprenoid biosynthesis required for protein isoprenylation.
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PMID:Inhibition of isoprenoid biosynthesis and the post-translational modification of pro-p21. 218 Sep 59


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