Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the effect of long-term thyrotoxicosis on muscle mitochondria, we measured representative mitochondrial enzymes from three different types of skeletal muscle (fast-twitch red and fast-twitch white from the quadriceps, and slow-twitch red from the soleus) in rats given 3 mg L-thyroxine and 1 mg triiodo-L-thyronine per kilogram of diet for 12 wk. Marker enzymes of the electron transport chain and citric acid cycle (cytochrome oxidase, cytochrome c, and citrate synthase) increase approximately twofold in soleus muscle in response to this treatment. The fast-twitch muscles exhibit no more than 44% increases in these enzymes in response to the same treatment. Relative to initial concentration, 3-hydroxybutyrate dehydrogenase increased to the same extent in fast-twitch red muscle as it did in the soleus (70%). Mitochondrial alpha-glycerophosphate dehydrogenase increased 76% in red quadriceps and 170% in soleus, but did not change in white muscle in the thyrotoxic rats. This differential sensitivity of the three types of muscle provides a tool for studying the mechanisms underlying the action of thyroid hormones on muscle mitochondria.
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PMID:Response of mitochondria of different types of skeletal muscle to thyrotoxicosis. 19 5

In isolated hepatocytes from normal fed rats, the subcellular distribution of malate, citrate, 2-oxoglutarate, glutamate, aspartate, oxaloacetate, acetyl-CoA and CoASH has been determined by a modified digitonin method. Incubation with various substrates (lactate, pyruvate, alanine, oleate, oleate plus lactate, ethanol and aspartate) markedly changed the total cellular amounts of metabolites, but their distribution between the cytosolic and mitochondrial compartments was kept fairly constant. In the presence of lactate, pyruvate or alanine, about 90% of cellular aspartate, malate and oxaloacetate, and 50% of citrate was located in the cytosol. The changes in acetyl-CoA in the cytosol were opposite to those in the mitochondrial space, the sum of both remaining nearly constant. The mitochondrial acetyl-CoA/CoASH ratio ranged from 0.3-0.9 and was positively correlated with the rate of ketone body formation. The mitochondrial/cytosolic (m/c) concentration gradients for malate, citrate, 2-oxoglutarate, glutamate, aspartate, oxaloacetate, acetyl-CoA and CoASH averaged from hepatocytes under different substrate conditions were determined to be 1.0, 8.8, 1.6, 2.2, 0.5, 0.7, 13 and 40, respectively. From the distribution of citrate, a pH difference of 0.3 across the inner mitochondrial membrane was calculated, yet lower values resulted from the m/c gradients of 2-oxoglutarate, glutamate and malate. The mass action ratios for citrate synthase and mitochondrial aspartate aminotransferase have been calculated from the metabolite concentrations measured in the mitochondrial pellet fraction. A comparison with the respective equilibrium constants indicates that in intact hepatocytes, neither enzyme maintains its reactants at equilibrium. On the assumption that mitochondrial malate dehydrogenase and 3-hydroxybutyrate dehydrogenase operate near equilibrium, the concentration of free oxaloacetate appears to be 0.3-2 micron, depending on the substrate used. Plotting the calculated free mitochondrial oxaloacetate concentration against the citrate concentration measured in the mitochondrial pellet yielded a hyperbolic saturation curve, from which an apparent Km of citrate synthase for oxaloacetate in the intact cells of 2 micron can be derived, which is comparable to the value determined with purified rat liver citrate synthase. The results are discussed with respect to the supply of substrates and effectors of anion carriers and of key enzymes of the tricarboxylic acid cycle and fatty acid biosynthesis.
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PMID:Distribution of metabolites between the cytosolic and mitochondrial compartments of hepatocytes isolated from fed rats. 68 Jun 39

1. Enzyme activities (units/g wet wt.) were determined in the caput and cauda epididymidis and in epididymal spermatozoa of the rat. 2. The activity of most enzymes in the cauda was between 50 and 100% of that in the caput, except that ATP citrate lyase was barely detectable in the cauda. 3. Spermatozoa, unlike epididymal tissue, contained sorbitol dehydrogenase but lacked ATP citrate lyase. NADP+-malate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, succinate dehydrogenase, carnitine acetyltransferase and citrate synthase were 5 to 400 times as active in spermatozoa as in epididymal tissue. 4. 2-Oxoglutarate dehydrogenase was the least active member of the tricarboxylic acid cycle in all tissues and most closely matched the measured flux through the cycle. 5. The concentrations of hydroxyacyl-CoA dehydrogenase and carnitine palmitoyltransferase were equivalent to the more active enzymes of the tricarboxylic acid cycle, indicating the capacity for extensive lipid oxidation, and the presence of 3-hydroxybutyrate dehydrogenase suggests that these tissues can also oxidize ketone bodies. 6. Transfer of reducing equivalents from cytoplasm to mitochondrion is unlikely to occur by means of the glycerol phosphate cycle because mitochondrial glycerol 3-phosphate dehydrogenase is relatively inactive in epididymal tissue, whereas the cytoplasmic enzyme has little activity in spermatozoa, but transfer may be accomplished by the malate-aspartate shuttle. 7. Transfer of acetyl units from mitochondrion to cytoplasm could be effected by the pyruvate-malate cycle in the caput of androgen-maintained rats, but not in the other tissues because of the low activity of ATP citrate lyase. Acetyl unit transfer could take place via acetylcarnitine, mediated by carnitine acetyltransferase. 8. Castration resulted in a decrease in the concentration of nearly all enzymes, although subsequent administration of testosterone restored concentrations to values similar to those in animals maintained by endogenous androgen. The extent to which enzyme concentration was changed by an alteration in androgen status was highly variable, but was most marked in the case of pyruvate carboxylase.
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PMID:Activity and androgenic control of enzymes associated with the tricarboxylic acid cycle, lipid oxidation and mitochondrial shuttles in the epididymis and epididymal spermatozoa of the rat. 72 83

The effects of aging on the oxidation of labeled glucose and 3-hydroxybutyrate and on several mitochondrial enzymes in rat brain were investigated. The oxidation of labeled glucose and labeled 3-hydroxybutyrate was diminished by about 40 and 35%, respectively, in cerebral cortex slices from 2-year-old rats compared to those from 3-mo-old animals. A significant reduction in the activities of 3-hydroxybutyrate dehydrogenase, 3-oxo acid CoA transferase, acetoacetyl CoA thiolase, and NAD-isocitrate dehydrogenase was observed in brains of 1- and 2-year-old rats compared to 3-mo-old animals. However, aging had no effect on the activities of citrate synthase and pyruvate carboxylase. These findings show that specific alterations occur in the activities of several mitochondrial enzymes in aging brain.
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PMID:Age-dependent changes in the oxidative metabolism in rat brain. 91 4

The maximum activities of some key enzymes of metabolism were studied in lungs of fed and 48-h-starved rats. The maximum activity of hexokinase in the lung is similar to that of other tissues of the body, but lower than that of phosphorylase and 6-phosphofructokinase. High activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were found in lung tissue, suggesting the importance of the pentose phosphate pathway in the lung. The activities of hexokinase and 6-phosphofructokinase were decreased whereas that of phosphorylase increased in response to starvation. Of the enzymes of the tricarboxylic acid cycle whose activities were measured, that of oxoglutarate dehydrogenase was the lowest, yet its activity (approximately 4.2 nmol/min per mg protein at 37 degrees C) was considerably greater than the flux through the cycle (0.46 nmol/min per mg protein at 37 degrees C; calculated from oxygen consumption by incubated lung slices). The activities of both oxoglutarate dehydrogenase and citrate synthase were decreased by starvation. The activities of 3-oxoacid CoA-transferase and acetoacetyl-CoA thiolase were low in lung tissue compared to those of other tissues (eg kidney, brain) and that of 3-hydroxybutyrate dehydrogenase was very low. The activity of carnitine palmitoyl transferase is higher in the lung, suggesting that fatty acids (and possibly acetoacetate) could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. Very low rates of utilization of 3-hydroxybutyrate were observed during incubation of lung slices, but that of oleate was 1.2 nmol/h per mg of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by lungs of the rat. 176

The rate of utilization of pyruvate (at various concentrations) was measured in lymphocytes prepared from rat mesenteric lymph nodes. The quantitative contribution of pyruvate to CO2, lactate, aspartate, alanine, citrate, acetate, acetyl-CoA and ketone bodies accounted for the pyruvate metabolized. Pyruvate utilization was depressed by increasing concentrations of pyruvate. The maximum catalytic activities and selected intracellular distributions of the following enzymes of pyruvate, citrate and acetyl-CoA metabolism were measured: citrate synthase, ATP-citrate lyase, lactate dehydrogenase, acetyl-CoA hydrolase, acetylcarnitine transferase, NAD+- and NADP+- isocitrate dehydrogenases, HMG-CoA lyase, HMG-CoA synthase, Pyruvate dehydrogenase, acetoacetyl-CoA thiolase, 3-oxoacid-CoA transferase, 3-hydroxybutyrate dehydrogenase and pyruvate carboxylase. Acetyl-CoA formed from pyruvate did not contribute to the respiratory energy metabolism of resting lymphocytes. Instead acetyl-CoA was converted to acetoacetate by reactions which may favour the pathway catalyzed by acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. Acetate, acetyl- and palmitoyl-carnitine inhibited the decarboxylation of [1-14C] pyruvate. These observations may be connected with the suppression of pyruvate utilization by increased pyruvate substrate concentration. Only very small amounts of either pyruvate or acetate were incorporated into lipids in resting lymphocytes. The amounts incorporated were partitioned in approximately the same pattern into FFA, T.G., cholesterol and cholesterol esters. Taken together the data show that pyruvate metabolism is directed inter alia at the formation of acetoacetate which may serve as a lipid synthesis precursor. When pyruvate utilization and metabolism was enhanced by concanavalin A, then acetoacetate formation was not favoured and from this it is proposed that the acetyl units may then be directed into lipid synthesis and may also make a contribution to the energy metabolism of the activated lymphocyte.
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PMID:Pyruvate metabolism by lymphocytes: evidence for an additional ketogenic tissue. 261 47

Tibialis anterior (TA) muscles of four small mammals were subjected to chronic nerve stimulation for 28 days (10 Hz, 10 hours per day). Total cellular activities of phosphofructokinase (PFK), hexokinase (HK), citrate synthase (CS), 3-hydroxy-acyl-CoA dehydrogenase (HADH) and 3-hydroxybutyrate dehydrogenase (HBDH) were measured in the stimulated and unstimulated contralateral muscles. Normal TA muscles displayed ranges of oxidative and glycolytic capacities with rabbit TA showing the lowest and mouse TA the highest oxidative capacity. Chronic stimulation was almost without effect in mouse TA. In all other species, glycolytic capacity was decreased and reference enzymes of aerobic-oxidative pathways were increased. Rabbit TA displayed the highest increment in oxidative capacity with approximately three-fold increases in CS and HADH and eleven-fold increases in HBDH. Different responses were also observed for HK. In some cases, the extent of adaptation appeared to be independent of the initial enzyme activity levels, while in other cases it appeared to follow an order which corresponded to the size of the animals. Thus, there exist species-specific ranges of adaptation and adaptive alterations in one species may not necessarily reflect the adaptive response of another species.
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PMID:Specific effects of low-frequency stimulation upon energy metabolism in tibialis anterior muscles of mouse, rat, guinea pig and rabbit. 297 3

The effect of undernutrition from the 16th day of pregnancy up to 70th day of life on blood glucose and ketone bodies and on several brain mitochondrial enzymes related to energy metabolism or biosynthetic function was investigated. Undernutrition in perinatal period was established by means of a food restriction to pregnant rats and, later, to the lactating mother; undernourished postweaned rats received half the diet consumed by the controls. Body and brain weight from undernourished rats was less than controls throughout the entire period studied. Glycemia and ketonemia were also always lower than controls. Cytochrome c oxidase, citrate synthase, 3-hydroxybutyrate dehydrogenase, 3-oxoacid coenzyme A transferase, and acetoacetyl-coenzyme A thiolase activities during the suckling period were in most stages lower than controls; subsequently, activities in undernourished rats reached or surpassed the control values. These results could explain the "catch up" phenomenon in several ultrastructural parameters found by other authors in undernourished postweaned rats.
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PMID:Glycemia, ketonemia, and brain enzymes of ketone body utilization in suckling and adult rats undernourished from intrauterine life. 298 52

Tibialis anterior (TA) muscle of mouse, rat, guinea pig, and rabbit was indirectly stimulated for 10 h/day at 10 Hz up to 28 days. Changes in the activity levels of hexokinase (HK), phosphofructokinase (PFK), glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), creatine kinase (CK), citrate synthase (CS), malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HADH), and beta-hydroxybutyrate dehydrogenase (HBDH) were compared. Although the direction of changes in the enzyme activity pattern was in accordance with previous findings on rabbit TA, the magnitude of the responses varied markedly between the mammals under study. Mouse TA was almost unaffected. A major effect of chronic stimulation in rat, guinea pig and rabbit was an increase in enzyme activities of aerobic-oxidative metabolism. According to intrinsic differences of the muscles under study, the increases varied among the species and appeared to be inversely related to the basal levels of these enzymes in the unstimulated muscles. Conversely, glycolytic enzyme activities (PFK, GAPDH, LDH) markedly decreased in rat, guinea pig, and rabbit, and were only slightly reduced in mouse. Changes in HK and HBDH activities displayed the largest variations in the induced change between species. These results indicate species-specific patterns of metabolic adaptation to increased contractile activity.
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PMID:Species-specific effects of chronic nerve stimulation upon tibialis anterior muscle in mouse, rat, guinea pig, and rabbit. 317 88

Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.
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PMID:Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages. 380 Sep 71


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