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32 records · Page 2Linked to original sources
PubMed1977

Biochemical background of atherosclerotic heart lesion in an experiment.

The authors investigated enzymic systems and corresponding substrate cycles that transport hydrogen across the mitochondrial membrane in a myocardium with experimental cholesterol-induced atherosclerosis. Sensitive spectrophotometric methods were used for assessing the activities of cytoplasmic and mitochondrial enzymes: lactate and alpha-glycerphosphate dehydrogenases, and of characteristic mitochondrial enzymes: glutamate and beta-hydroxybutyrate dehydrogenases. Specific enzymological methods were used in determining the concentrations of lactic, pyruvic, glycerophosphoric, dihydroacetonephosphoric, malic, oxaloacetic, glutamic, alpha-ketoglutaric, acetoacetic, and beta-hydroxybutyric acids. The cytoplasmic NAD/NADH quotient was calculated. The investigators found a reduction of enzymic activities in the "shuttle" transport system studied, marked deviations from normal levels of their substrates, and a reduction of the NAD/NADH quotient by the factor 0.56. All these phenomena represent a biochemical background of a complex of symptoms characterizing severe myocardial lesion in experimental atherosclerosis.

Animals↗
PubMed1975

Changes in enzyme pattern of Ehrlich ascites tumor cells following serial cultivation in media with increased (hypertonic) NaCl content.

Adaptation of Ehrlich ascites tumor cells to serial cultivation in media with progressively elevated (hypertonic) NaCl content ("high NaCl"-tolerant cells) has resulted in progressive increases of the cellular activities of NAD-dependent glycerol-3-phosphate dehydrogenase (EC 1.1.1.8), NAD-dependent malate dehydrogenase (EC 1.1.1.37), glutamate--oxalacetate transaminase (EC 2.6.1.1), NAD (P)-dependent glutamate dehydrogenase (EC 1.4.1.3), NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42). The activities of glutamate-pyruvate transaminase (EC 2.6.1.2.) and of glycolytic enzymes as phospho-fructokinase (EC 2.7.1.11), glyceraldehydephosphate dehydrogenase (EC 1.2.1.12) and lactate dehydrogenase (EC 1.1.1.27) were only slightly and not in progressive manner (in response to the progressive increase of the environmental NaCl concentration) affected. These changes are discussed with respect to a metabolic pattern of these "high NaCl"-tolerant cells which is compatible with increased energy requirements, especially for active cation transport. It is suggested that these increased cellular enzyme activities reflect an increased transfer of reducing equivalents across mitochondrial membranes (via the "glycerophosphate cycle and the malate-aspartate shuttle") and possibly a stimulated lipid metabolism. These alterations in the level of enzyme activities must be regarded asan adaptive cellular response to the "high NaCl" environment, since readaptation to growth in regular isotonic media resulted in a reversion to the enzyme pattern characteristic of the parent cells.

Alanine Transaminase↗
PubMed1976

Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings.

The authors report 2 familial cases of neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in the liver. In both cases, disorders started immediately after birth and were characterized by major neurological symptoms, acute metabolic acidosis with hyperketonemia and hyperammonemia. Course was rapidly fatal despite intensive care, bicarbonate therapy and several therapeutic attempts with biotin and thiamine. Hyperlactacidemia was associated with dramatic increase in lactate/pyruvate ratio, without anoxia, in contrast with decreased beta hydroxybutyrate/acetoacetate ratio. This unusual metabolic pattern may be assumed to result from decreased oxaloacetate synthesis as a result of pyruvate carboxylase deficiency, and impairment of oxaloacetate dependent mitochondrial redox shuttles. Post mortem enzymatic study of the liver and kidney showed biotin unresponsive total deficiency of pyruvate carboxylase. Other gluconeogenic enzyme activities were normal.

Acetoacetates↗
PubMed1976

Evaluation of redox state of isolated perfused rat lung.

The metabolic responsiveness of lung tissue to inhibition of oxidative metabolism was determined by measurement of the redox state of the isolated perfused and ventilated rat lung. Changes in redox state were evaluated by fluorescence from the lung surface at wavelengths suitable for reduced pyridine nucleotides and by measurement of the ratios of redox couples in rapidly frozen lung tissue. Maximal change of redox state was observed during ventilation with carbon monoxide; surface fluorescence increased 6.6%, lactate/pyruvate increased 5.8 times, glycerol 3-P/dihydroxyacetone-P increased fourfold and glutamate/alpha-ketoglutarate doubled. KCN infusion resulted in similar changes. Hypoxia produced with N2 ventilation resulted in less than maximal changes in redox couple ratios until alveolar PO2 was reduced below 0.1 mmHg. Redox changes observed during infusion of 0.5 mM aminoxyacetic acid suggested that maintenance of cytoplasmic redox state depended on functioning of a malate-aspartate "shuttle." The isolated perfused lung appears suitable to study factors controlling pulmonary parenchymal oxidative metabolism. The results emphasize the need for ventilation with CO to establish intracellular anoxia.

Amobarbital↗
PubMed1975

Effect of different regimens of early malnutrition on behavioural development and adult avoidance learning in Swiss white mice.

1. The effects of perinatal malnutrition on behavioural development and adult shuttle-box avoidance performance were studied in Swiss white mice. 2. Mice were malnourished (a) from the 7th day of gestation until birth, (b) from birth until weaning, or (c) during both gestation and the sucking period. 3. Pups born of protein-restricted mothers had reduced birth weights, retarded development and poor adult avoidance performance, even if reared from birth by well-nourished mothers. 4. Postnatal malnutrition, induced either by restricting maternal diet or by rearing in large litters, retarded development during the second half of lactation and lowered subsequent adult avoidance performance.

Animal Nutritional Physiological Phenomena↗
PubMed1975

Interaction of ethacrynic acid with control sites of renal glucose metabolism.

Ethacrynic acid stimulates in vitro concentration dependent renal gluconeogenesis from substrates which enter the gluconeogenic pathway at the level of the triosephosphates like glycerol or fructose or from substrates which have to pass the oxaloacetate shuttle like pyruvate or from intermediary products of fatty acid oxydation or citrate cycle. Our results suggest that a site of action of ethacrynic acid in this metabolic aspect is the enzyme system fructose diphosphatase/frutose-6-phosphate kinase and eventually additionally pyruvate carboxylase.

Acetoacetates↗
PubMed1979

Effects of glutamine deprivation on glucose and amino acid metabolism in tissue culture.

The effects of glutamine deprivation on cultured skeletal muscle cells were analyzed by incubating 10-day-old myotube preparations in glutamine free Dulbecco's modified Eagle medium containing 10% fetal calf serum for up to 48 h. Under these conditions net glutamine production was not observed, but active ammonia production (average rate = 1.0 nmol/min . mg protein) continued despite glutamine withdrawal. Glutamine deprivation was associated with a progressive depletion of intracellular aspartate and glutamate. Maximal aspartate depletion correlated with a 15-fold increase in the intracellular lactate:pyruvate ratio and a 3-fold decrease in the estimated intracellular glutamate:(alpha-ketoglutarate) (ammonia) ratio. Despite wide shifts in cell metabolite concentrations, the mass action ratios of alanine and aspartate aminotransferase approximated the expected equilibria constants. These results suggest that 1) glutamine deprivation is associated with a marked reduction of aspartate, and the maintenance of aspartate depletion is due in part to the tendency of aspartate aminotransferase to maintain the metabolites of this reaction at a near equilibrium level; 2) the transport of reducing equivalents from the cytosolic to the mitochondrial compartments via the malate-aspartate shuttle may be limited under conditions of aspartate depletion.

Amino Acids↗
PubMed1976

Glycerol phosphate shuttle in virus-transformed cells in culture.

The glycerol phosphate shuttle is shown not only to be present and functional in virus-transformed cells, but its level is higher than in normal cells in culture. The increased aerobic glycolysis that has been demonstrated for these cells after transformation, therefore, is not due to an impairment of hydrogen transfer pathways.

Avian Sarcoma Viruses↗
PubMed1979

Comparsions among VO2 max values for hockey players and runners.

This study was designed to investigate the specificity of the VO2 max response of runners and hockey players for multistage tests done on the treadmill (RUN) or on the ice, skating a shuttle 20m course with (20m+) or without equipment (20m-) and a 140m oval course (140m-). Hockey players VO2 max in ml.kg-1.min-1 (n=10) were similar for the 4 tests (RUN: X +/- SD = 61.4 +/- 6.3; 140m-: 62.1 +/- 9.4; 20m-: 58.6 +/- 6.4; and 20m+: 59.9 +/- 7.4). VO2 max of runners (n = 10) were superior on the treadmill (68.6 +/- 4.5) as compared to the ice (140m-: 65.6 +/- 5.4). Hockey players as compared to runners, were 15% more efficient on the ice and 7.9% less efficient on the treadmill. The equipment increased the energy cost of skating by 4.8% and decreased the multistage test time by 20.3%. The low temperature arena as compared to the standard temperature laboratory, yielded lower heart rate response with multistage tests. Blood lactates (mg%) were similar for all tests done with hockey players (RUN: 128.3 +/- 19.3; 140m-: 126.8 +/- 14.7; 20m-: 133.0 +/- 17.5; and 20m+: 131.4 +/- 18.5), but lower on the ice (140m-: 87.7 +/- 15.9) as compared to the treadmill (127.2 +/- 26.4) for the runners. Maximal skating speed disclosed a relatively homogenous group of hockey players but their VO2 max scores were more widely distributed.

Adult↗
PubMed1977

Alterations of serum enzymes during therapy directed at human malignant sarcomas: a radiological follow-up study of tumor transformation.

1. When a malignant growth is developing in a patient, one often observes in the serum an increased activity of serum enzymes due to necrosis and increased membrane permeability caused by the altered metabolism of malignant cells. Conversely, I considered it interesting to check the enzymes of the malate-aspartate shuttle in addition to LDH enzyme when a neoplastic growth is regressing due to radiation therapy. The patients who were selected for this study had histologically proved sarcomas (reticulosarcoma, liposarcoma, and post-nosal sarcoma). 2. The data obtained indicated that tumor regression is heralded by progressive decline (to the normal level) of LDH, GOT and MDH activities in serum. Normalization of these systems suggested that reticulosarcoma, liposarcoma, and post-nosal sarcoma are sensitive to the therapeutic agent used. 3. In viewing the data herein reported a definitive conclusion regarding the diagnostic usefulness of these assays is apparent. It seems possible that the measurement of these enzymes in serum of patients with proved sarcomas, may prove to be useful laboratory adjunct to diagnostic radiology and in the management of patients whose diagnosis has already been established.

Aspartate Aminotransferases↗
PubMed2026

Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with limited therapeutic options. The circulating metabolome comprises small molecules present in plasma/serum which are the intermediates and end-products of cellular metabolism, and is linked to ALS pathogenesis. METHODS: We conducted hypothesis-free two-sample Mendelian randomisation (MR) analysis of the concentration of 575 plasma/serum metabolites, to determine which are causally linked to risk of ALS. Significant metabolites were validated in an independent GWAS of plasma/serum metabolite concentrations and evaluated for sex-specific effects. Correlations between directly measured patient biofluid metabolite concentrations and ALS risk/severity were examined in 94 ALS patients and 40 controls. We experimentally assessed metabolic function in a murine neurons and human astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72. RESULTS: MR causally associated five metabolites with ALS risk after multiple-testing correction. Higher serum concentration of glycoprotein acetyls (P&#x2009;=&#x2009;9.7e&#x2009;-&#x2009;9, &#x3b2;&#x2009;=&#x2009;0.21) and the peptide DSGEGDFXAEGGGVR (P&#x2009;=&#x2009;8.0e&#x2009;-&#x2009;6, &#x3b2;&#x2009;=&#x2009;0.22) was associated with increased ALS risk, whereas higher plasma concentration of phenylalanylserine, isobutyrylcarnitine, and acetylcarnitine was protective (P&#x2009;<&#x2009;5e&#x2009;-&#x2009;5, &#x3b2;&#x2009;= -&#x2009;0.29 to&#x2009;-&#x2009;0.72). DSGEGDFXAEGGGVR has been linked to glucose metabolism but we have used genetic fine-mapping to link DSGEGDFXAEGGGVR, neuronal glucose uptake through GLUT3, and ALS risk. Direct measurement of metabolite concentrations in patient biofluids revealed elevated acetylcarnitine levels in patients with ALS, which were associated with delayed symptom onset (Cox regression, P&#x2009;=&#x2009;0.02, HR&#x2009;=&#x2009;0.4). Similarly, lactate is elevated in ALS patient CSF (ANOVA, P&#x2009;=&#x2009;1.3e&#x2009;-&#x2009;3) and in patients with longer survival time (Cox regression, P&#x2009;=&#x2009;0.03, HR&#x2009;=&#x2009;0.3). Plasma fructose is elevated in ALS patients with shorter survival time (Cox regression, P&#x2009;=&#x2009;0.02, HR&#x2009;=&#x2009;1.1). In vitro, neurons and astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72 demonstrated reduced metabolic flexibility. CONCLUSIONS: We provide evidence that impaired energy substrate availability contributes to ALS risk and severity. CNS cell types differ in their use of energy substrates and therefore we postulate the relative importance of different cell types for different stages of disease. Our findings support further investigation of metabolic interventions to treat or prevent ALS.

Amyotrophic Lateral Sclerosis↗