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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two isozymes of fructose-6-phosphate kinase and two isozymes of pyruvate kinase have been detected in Escherichia coli under a wide variety of growth conditions. Their kinetic behavior has been characteriized with respect to different effectors and substrates. The conclusions reached on one hand by Malcovati and Kornberg (Biochim. Biophys. Acta (1969) 178, 420-423), on the other hand by Fraenkel, Kotlarz and Buc (J. Biol. Chem. (1973) 248, 4865-4866) have been found to be true in aerobiosis as well as in anaerobiosis. The biosynthesis of the four proteins is sensitive to the nature of the carbon sources as well as to the shift from aerobic to anaerobic conditions. Kinetics of depression after a shift to anaerobiosis have been followed and found to be of the order of the doubling time.
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PMID:Regulation of the amount and of the activity of phosphofructokinases and pyruvate kinases in Escherichia coli. 12 2

Human red cells were incubated at pH 8.2 and 30 mM phosphate concentration with glucose, glucose plus methylene blue, or inosine. In 16 normal subjects, the lactate production rate (LPR) from glucose alone was 92.2 +/- 7.5 mumoles per minute per liter red blood cell. With methylene blue added, the mean LPR was 118.5 +/- 7.4 per cent of control glucose values. With inosine as substrate the mean LPR was 68.5 +/- 6.0 per cent of that from glucose. Lactate/glucose ratios averaged 1.36, presumably because of accumulation of intermediates under conditions of high pH and Pi. Patients with various kinds of anemias had LPR's from glucose that were usually markedly higher than normal, but the LPR's from inosine were generally about 2/3 of those from glucose. The LPR's of the anemic patients correlated with their degree of reticulocytosis and several patients with pyruvate kinase (PK) deficiency showed normal LPR if the red cell population age was ignored, byt marked depression when compared to expected LPR for degree of reticulocytosis. The LPR from glucose of red cells of G6PD-deficient subjects was decreased (not increased) by methylene blue. Methylene blue, while stimulating the pentose phosphate pathway, also mediated some oxidation of NADH, thus complicating the stoichiometry of the overall system. In addition, the results suggested that the dye may have attacked -SH groups on some enzymes. In normal red cells, the lower LPR from inosine than from glucose was explained as due to consumption of ATP for hexose utilization (thus generating more ADP for the triose reactions). In confirmation, when red cells were incubated without substrate to deplete their ATP-, and enhance their ADP-, levels, the LPR from inosine exceeded that from glucose. Fluoride and iodoacetate affected LPR from glucose more than from inosine, suggesting the necessity of adequate ATP levels in hexose utilization. Overall glycolysis in the red cell is seen as the resultant of a network of metabolic reactions in which ADP and ATP levels are important control parameters.
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PMID:Incubation studies on human red cells utilizing glucose or inosine under various conditions. 24 Aug 98

Glucagon and L-epinephrine stimulate gluconeogenesis from 20 mM L-lactate, the effect being about 3 times greater in liver cells from fed rats than in those from fasted rats. The rate of pyruvate kinase flux was estimated to be less than 10% of the rate of gluconeogenesis from lactate in hepatocytes from fasted rats, and neither glucagon nor epinephrine lowered the absolute rate significantly. In hepatocytes from fed rats, however, the rate of pyruvate kinase was nearly one-half that of gluconeogenesis. Glucagon caused a marked depression of pyruvate kinase flux, with 1 muM glucagon lowering the rate to nearly the level found in cells from fasted rats Epinephrine at concentrations from 10(-8) to 10(-6) M actually increased pyruvate kinase flux during gluconeogenesis from lactate in cells from fed rats. These results are in accord with the view that the effects of glucagon and epinephrine on gluconeogenesis are not identical.
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PMID:Role of pyruvate kinase in the regulation of gluconeogenesis from L-lactate. 84 45

6-Phosphofructo-2-kinase (PFK-2) was analyzed in four organs of the anoxia-tolerant marine gastropod mollusk Busycon canaliculatum. Whelk PFK-2 resembled the nonhepatic enzyme from mammals with highest activity occurring in gill (22 pmol.min-1.g-1). Hepatopancreas PFK-2 was purified over 8,000-fold to a final specific activity of 11 mU/mg protein (at 20 degrees C) and gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was a dimer with a native molecular mass of 142 kDa and a subunit molecular mass of 67 kDa. The purified enzyme showed negligible fructose-2,6-bisphosphatase (FBPase-2) activity, although the activity ratio of PFK-2 to FBPase-2 was 0.625 in crude extracts. In response to environmental anoxia, the activity of PFK-2 dropped in all organs to 34-56% of the corresponding aerobic value (half-time was 2 h in gill), and the Michaelis constant for fructose 6-phosphate increased by 50% (to 92 microM in gill). These changes paralleled decreases in organ fructose 2,6-bisphosphate concentration and pyruvate kinase activity and contribute to the overall glycolytic rate depression induced by anoxia in this facultative anaerobe. In vitro treatment of the anoxic form of hepatopancreas PFK-2 with alkaline phosphatase increased enzyme activity, suggesting that the aerobic and anoxic enzyme forms are interconverted by reversible protein phosphorylation. However, the protein kinase involved in this process is not yet known; incubation of aerobic PFK-2 with Mg-ATP plus adenosine 3',5'-cyclic monophosphate-dependent protein kinase or protein kinase C did not alter enzyme activity.
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PMID:Inactivation of 6-phosphofructo-2-kinase during anaerobiosis in the marine whelk Busycon canaliculatum. 164

In anaerobically grown yeast cells which lack functional mitochondria, the presence of diethylstilbestrol (DES) depressed glycolysis. The addition of the inhibitor markedly increased the cellular concentration of glycolytic intermediates which are formed prior to the pyruvate kinase step as well as to bring about an increase in the [ATP]/[ADP] ratio. Under these conditions an 18 fold decrease in the mass action ratio for pyruvate kinase [( pyruvate] [ATP]/[phosphoenolpyruvate] [ADP]) was noted, however, there was little if any effect on the other glycolytic enzymes. These results suggest that the depression of anaerobic glycolysis caused by DES results from a blockage at the level of the regulatory enzyme pyruvate kinase through a modification of its intracellular environment.
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PMID:Inhibition of glycolysis induced by diethylstilbestrol in anaerobically grown yeast. 269 93

Kinetic properties of regulatory enzymes of glycolysis in liver of the mouse, Zapus hudsonius, were modified during hibernation, the probable mechanism being covalent modification. Liver glycogen phosphorylase activity was strongly depressed during both short (less than 24 h) and long (5-8 days) term hibernation, the mechanism involving a decrease in both the percentage of enzyme in the active a form and the total amount (a + b) of enzyme expressed. Phosphofructokinase showed kinetic changes (a 2.5-fold increase in Ka for fructose-2,6-P2, 4- and 3.7-fold decreases in I50 values for ATP and citrate, compared to euthermic controls) in liver of hibernators indicative of phosphorylation inactivation of the enzyme. Measured levels of fructose-2,6-P2 in liver did not change during hibernation. Changes in pyruvate kinase kinetics in liver from long term hibernators similarly indicated enzyme phosphorylation in the depressed state (Ka for fructose-1,6-P2 increased 4.4-fold, I50 for L-alanine decreased 6.3-fold). Apparent covalent modification of glycolytic enzymes during hibernation may serve two functions: depression of glycolytic activity as part of the general metabolic rate depression of hibernation, or reorganization of fuel use in the hibernating state to limit carbohydrate catabolism and promote gluconeogenesis.
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PMID:Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation. 294 58

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.
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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.
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PMID:Organ-specific control of glycolysis in anoxic turtles. 297 50

Aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase, and pyruvate kinase activities were determined in erythrocytes of various ages, separated by Percoll gradient centrifugation, in 13 alcoholic patients and eight control subjects. The total erythrocyte activities of all three enzymes were not affected by alcoholism, however, the youngest cells of alcoholics had a decreased aldehyde dehydrogenase activity, while both glucose-6-phosphate dehydrogenase and pyruvate kinase activities were increased. The depression of aldehyde dehydrogenase activity not only persisted, but became more marked after 2 weeks of abstinence, while the enhanced activities of the two other enzymes returned to normal. These observations suggest that chronic alcohol ingestion suppresses aldehyde dehydrogenase in the bone marrow, while it enhances other erythrocytic enzymes.
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PMID:Changes in erythrocyte enzyme activities during erythrocyte aging in alcoholism. 304 74

In response to added catecholamines, isolated trout (Salmo gairdneri) hepatocytes substantially increase the output of glucose into the surrounding medium. This effect is due to activation of glycogen breakdown concomitant with increases in gluconeogenesis and cell respiration. Each metabolic parameter is activated to a similar extent. In hormone-treated and untreated cells, glycogenolysis accounts for more than 97% of glucose production. Activation of glycogen phosphorylase is implicated in the degradation of cell glycogen, while increased flux through the gluconeogenic pathway from lactate is associated with inactivation of pyruvate kinase, possibly through enzyme phosphorylation as indicated by the activity ratio measured at low and saturating concentrations of phosphoenolpyruvate. From studies with specific adrenergic agonists and antagonists, we conclude that stimulation of glycogenolysis and gluconeogenesis in trout hepatocytes is consistent with a beta-adrenergic effect. Results are inconclusive with respect to catecholamine-mediated activation of cell respiration. None of the monitored cell acid-base variables (pH, PCO2, [HCO3-]) are implicated in the catecholamine-dependent changes in metabolic output of hepatocytes. Imposed hypercapnic conditions (increased medium PCO2 and decreased medium pH), which cause changes in cell acid-base parameters, result in a depression of lactate oxidation and gluconeogenesis, while the rate of glycogenolysis is not affected. In addition, the total amounts of glycogen phosphorylase and pyruvate kinase assayable are negatively affected by hypercapnic treatment of hepatocytes. Under hypercapnic conditions, cells are highly responsive to adrenergic agonists. It appears that--especially in the long term--the catecholamine-dependent activation of gluconeogenesis may compensate for the acid-base-dependent shortfall in glucose output by the liver.
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PMID:Interactive effects of catecholamines and hypercapnia on glucose production in isolated trout hepatocytes. 313 Nov 87


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