Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiration and glycolysis of pig platelets suspended in a dialyzed plasma were studied at various hydrogen ion concentrations. Respiration of platelets was high at acidic pH and decreased at physiological pH. This pH profile may not be attributed to properties of mitochondria, since the respiratory rate of mitochondria prepared from platelets was maximal at physiological pH. A low respiratory rate at physiological pH seemed to be attributable to depression of respiration by glycolysis, since the addition of glucose further depressed the rate. The Crabtree effect was more prominent at alkaline ph. glycolysis increased with an increase in the pH of the plasma, contrary to oxygen comsumption. The Pasteur effect was less prominent at alkaline pH. The effect of pH on lactate production by the cytosol fraction of platelets was similar to that of whole platelets. The glycolytic intermediate pattern showed that phosphofructolinase was the committed step. Both ATP concentration and ATP formation calculated from respiratory and glycolytic rates were constant at various pH values. These observations may indicate that the pH primarily affects platelet glycolysis at the phosphofructokinase step and the respiration is secondarily controlled by glycolysis.
 ...
PMID:Effect of hydrogen ion concentration on energy metabolism in pig platelets. 23 23

Coma and other neurologic abnormalities are present in patients with either diabetic ketoacidosis (DKA) or nonketotic coma (NKC), and the cause of such phenomena are not known. Patients with NKC also manifest seizures and focal neurologic changes. Treatment of diabetic coma with insulin may induce cerebral edema by as yet undefined mechanism(s). In patients with DKA, cerebral oxygen utilization is impaired, and there is hyperviscosity of the blood. A substantial part of the brain's energy source is derived from ketones, which in themselves can depress sensorium. Extracellular hyperosomolality is present, which may also contribute to the genesis of coma. In addition, most ketoacidotic patients have associated medical conditions, which may further impair consciousness. Biochemical changes in the brains of animals with DKA include impairment of both phosphofructokinase activity and pyruvate oxidation, and accumulation of citrate. The net effect upon sensorium in ketoacidotic patients probably represents the interaction of most of the above factors and differs markedly among individuals. Patients with NKC manifest not only depression of sensorium, but also focal motor seizures, hemiparesis, and other neurologic changes, such as aphasia, hypereflexia, sensory defects, autonomic changes, and brainstem dysfunction. Most of the aforementioned changes revert to normal after correction of hyperosomolality. Gamma amino butyric acid, which has been shown to elevate the seizure threshold, is normal in brains of ketoacidotic animals, but may be low in nonketotic coma. Also, hyperosomolality per se may produce seizures. Cerebral edema may complicate the treatment of either DKA or NKC. The available experimental evidence suggests that many of the commonly held theories for the production of such brain swelling probably do not occur. There is no breakdown of the sodium pump, sorbitol or fructose do not accumulate in brain, and brain glucose is only about 25 percent of that in plasma; Cerebral edema is probably produced largely by a direct action of insulin on brain at a time when plasma glucose is approaching normal values. Cerebral edema can thus theoretically be avoided by stopping insulin when plasma glucose has been lowered to values approaching normal.
 ...
PMID:Neurologic manifestations of diabetic comas: correlation with biochemical alterations in the brain. 80 37

The oxygen consumption rate of Scapharca inaequivalvis measured under normoxic conditions over 48 h showed a significant daily cycle with lowest values occurring shortly after the dark period; all hypoxia exposure experiments were carried out during the declining part of the cycle. Animals were exposed to a constant level of hypoxia for a 12-h period in a series of 14 experiments, each at a different oxygen tension. The oxygen consumption was measured continuously, and the extent of accumulation of end-products (succinate and propionate), and the inhibitory effect of adenosine triphosphate on phosphofructokinase were determined at the end of exposures. All three parameters (oxygen consumption, end-product accumulation, phosphofructokinase inhibition) showed a remarkable correlation with major changes occurring between 2.5 and 1.5 ppm (7 and 4 kPa) O2. The oxygen consumption rates showed a drop to 6% of the normoxic rate, but a consistent low consumption remained below 2 ppm (5.5 kPa) which partly recovered over the 12-h exposure period by about three-fold. Succinate and propionate accumulated progressively between 2.5 and 1.5 ppm (7 and 4 kPa); at [O2] less than 1.5 ppm (4 kPa) the concentration did not increase further, indicating that anaerobic metabolism had reached a maximum. Over the same range, phosphofructokinase showed an increased sensitivity for adenosine triphosphate, the lower inhibitor concentration at 50% Vmax value pointing to depression of glycolytic rate. Despite the activation of anaerobic metabolism and the evident depression of aerobic metabolism, simple calculation demonstrates that Scapharca inaequivalvis relies mainly on aerobic metabolism even during severe hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of long-term hypoxia on the energy metabolism of the haemoglobin-containing bivalve Scapharca inaequivalvis: critical O2 levels for metabolic depression. 138 37

Depression of carbohydrate digestion by oral administration of acarbose, a glucosidase inhibitor, led to a 75% inhibition of the re-activation of lipogenesis in vivo in the mammary gland of 18 h-starved lactating rats refed with 5 g of chow diet. Rates of [1-14C]glucose incorporation in vitro into lipid and CO2 in mammary-gland acini isolated from refed animals were elevated compared with acini from starved rats, but acarbose treatment completely prevented this stimulation. Gastric intubation of glucose led to a large stimulation of lipogenesis in the mammary gland of starved lactating rats, similar to that induced by refeeding with chow diet; this was dependent on the amount of glucose given and the time elapsed between glucose administration and injection of 3H2O for the measurement of lipogenesis. The switch-on of lipogenesis in the mammary gland of starved lactating rats, by refeeding or by intubation of glucose, was associated with a decrease in the ratio of [glucose 6-phosphate]/[fructose 1,6-bisphosphate] in the gland, indicative of an increase in phosphofructokinase activity. A time-course study revealed that the ratio decreased rapidly over the first 30 min of chow refeeding, after which a large surge in lipogenesis was seen. Acarbose, given 25 min after the onset of refeeding, led to a stepwise increase in the ratio, in parallel with the observed decrease in lipogenic activity. It is concluded that the control of lipogenesis in the mammary gland is closely linked to the availability of dietary carbohydrate. An important site of regulation of lipogenesis in the gland appears to be at the level of phosphofructokinase. A possible role of insulin in the regulation of phosphofructokinase activity, and the acute modulation of insulin-sensitivity in the gland during the starved-refed transition, are discussed.
 ...
PMID:The regulation of lipogenesis in vivo in the lactating mammary gland of the rat during the starved-refed transition. Studies wtih acarbose, a glucosidase inhibitor. 295 38

An examination of the kinetic parameters of phosphofructokinase, pyruvate kinase and glycogen phosphorylase, and the cellular concentration of fructose 2,6-bisphosphate during anoxia in the turtle Pseudemys scripta showed that the total activity of glycogen phosphorylase, and the phosphofructokinase inhibition constants for citrate and ATP were decreased in anoxic turtle brain. These results suggest that the ability of turtle brain to survive extended periods of anoxia is the result of metabolic rate depression regulated, at the molecular level, by enzyme inactivation through anoxia-induced covalent modification.
 ...
PMID:Anoxic brain function: molecular mechanisms of metabolic depression. 296 46

Control of glycolysis during anoxia was investigated in five organs (heart, brain, liver, and red and white skeletal muscles) of the freshwater turtle, Pseudemys scripta, after 1 or 5 h of submergence in N2-bubbled water. Lactate was produced as the metabolic end product, with distinct organ differences in the amount (net lactate accumulation was 2.4-fold higher in brain than white muscle) and rate (lactate production in liver dropped 16-fold after the 1st h) of lactate accumulation. ATP and total adenylate contents of all organs were reduced (by 15-32%) after 1 h of submergence, but energy charge was maintained; after 5 h, adenylate contents had fully recovered. Changes in the levels of hexose and triose phosphate intermediates of glycolysis indicated an activation of glycolysis within the 1st h of anoxia exposure in brain, heart, and skeletal muscles. By 5 h, however, these were reversed, and a glycolytic rate depression was indicated, consistent with the overall metabolic rate depression accompanying long-term anaerobiosis in the turtle. Crossover analysis indicated glycolytic control at the pyruvate kinase reaction in all organs during both glycolytic activation and metabolic depression; regulatory control at the phosphofructokinase locus was primarily important only during glycolytic activation in heart and red muscle. The same analysis indicated a very rapid glycolytic inhibition in liver occurring within the 1st h of anoxia exposure; this allows glycogenolysis to be directed toward glucose export yielding the fermentative fuel used by other organs during anoxia.
 ...
PMID:Organ-specific control of glycolysis in anoxic turtles. 297 50

Multiple infarcts were produced in cerebral hemispheres of rats by injecting calibrated 50-micron microspheres into the left internal carotid artery, and alterations in lipid and energy metabolism were evaluated 24 hours later in the embolized hemisphere. Total phospholipid content was decreased by 26%, but the different classes of phospholipids were not equally affected. Phosphatidylinositol and phosphatidylserine levels were decreased by about 40% and phosphatidylcholine and phosphatidylethanolamine by 25%, while sphingomyelin level remained unchanged. There was a 3.2-fold increase in total free fatty acid content with a relatively larger rise in polyunsaturated free fatty acids 20:4 and 22:6 (20-fold increase). Determination of enzyme activities showed decreases in Na+,K+-ATPase (-21%) and hexokinase (-14%) but no changes in phosphofructokinase and pyruvate kinase. Study of energy metabolism using the closed system method of Lowry et al showed a significant depression (-36%) of the cerebral metabolic rate. Taken together, these data suggest a relation between lipid alterations and dysfunction of energy metabolism. Phospholipid degradation with subsequent free fatty acid release and alteration in membrane-bound enzymes may have a direct effect on metabolic machinery and may slow cerebral metabolic rate.
 ...
PMID:Lipid metabolism, cerebral metabolic rate, and some related enzyme activities after brain infarction in rats. 356 99

An analysis of the glucose downshift mechanism in Bacillus subtilis has shown that the depression of catabolic enzymes characteristic of the 'glucose effect' includes isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase. Additionally, phosphofructokinase undergoes what appears to be a reversible modification regulated by glucose transport.
 ...
PMID:The glucose effect in Bacillus subtilis. 622 97

1. The activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase have been measured in the vastus lateralis and rectus abdominus muscle of normal human subjects and in very ill surgical patients. 2. The activities of these enzymes in the muscle of control subjects were similar to the pattern seen in the skeletal muscle of other mammals and lower vertebrates. 3. Fructose bisphosphatase and phosphofructokinase activities were significantly lower in the muscle of ill patients although the depression of the activity of fructose bisphosphatase was much greater than that of phosphofructokinase in both muscle types of ill patients. 4. The maximum rate of cycling in the fructose 6-phosphate--fructose, 1,6-diphosphate cycle may be altered in the ill. 5. This decreased cycling may have a direct influence on the sensitivity of glycolysis to regulators such as the adenine nucleotides and may reduce the ability to maintain body temperature. 6. Increased glycogen synthesis in these muscles may indicate that the role of fructose bisphosphatase is unlikely to be solely in glycogen resynthesis.
 ...
PMID:Activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase in muscle of normal subjects and very ill surgical patients. 626 37

Malnourished surgical patients have metabolic and functional abnormalities of skeletal muscle and it has been suggested that these are due to reduced activities of glycolytic enzymes associated with abnormalities of muscle fibres. We have measured the activities of four key enzymes of glucose utilization and the size and distribution of muscle fibre types in vastus lateralis biopsies from 14 undernourished patients awaiting surgery (mean weight loss 24 +/- 10 per cent). These results were compared with those from 14 normally nourished controls, comparable in age, sex, race and habitual activity. Fructose bisphosphatase activity was reduced in undernourished patients by 44 per cent (P less than 0.01), phosphofructokinase by 40 per cent (P = 0.005) and hexokinase by 37 per cent (P less than 0.001). Both fibre types were smaller in patients than controls (area I, 41.4 micron2 X 10(-2) +/- 0.4 vs. 73.3 micron2 X 10(-2) +/- 0.6, less than 0.001; area II, 27.7 micron2 X 10(-2) +/- 0.4 vs. 72.5 micron2 X 10(-2) +/- 0.5, P less than 0.001), and there was a smaller proportional number of type II fibres in patients (35 per cent vs. 65 per cent, P less than 0.01). This loss of type II fibre numbers and preferential type II atrophy may account for the enzyme depression associated with it and could produce the syndrome of impaired glucose tolerance, muscle weakness and fatigue seen in undernourished patients. In a subgroup of 11 patients, biopsy was repeated after 14 days of intravenous nutrition. Only phosphofructokinase activity rose significantly (19.62 +/- 1.85 to 30.74 +/- 2.99 mumol min-1 g-1, P less than 0.01) and both type II fibre size (40.6 +/- 18.5 to 47.4 micron2 +/- 20.3 X 10(-2), P less than 0.05) and number (42 per cent +/- 6 to 56 per cent +/- 5, P less than 0.05) also rose. Intravenous nutrition may therefore increase maximum glycolytic rate and improve muscle function in undernourished surgical patients.
 ...
PMID:Abnormalities of muscle metabolism and histology in malnourished patients awaiting surgery: effects of a course of intravenous nutrition. 632 97


1 2 Next >>