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[Synthesis of tyrosine and 3,4-dihydroxyphenylalanine by Citrobacter freundii bacteria from lactic acid].

A possibility of using lactic acid as a precursor for the synthesis of L-tyrosine and L-3,4-dihydroxyphenylalanine (DOPA) by Citrobacter freundii 62 and 63 was established. The synthesis of tyrosine from lactic acid occurs at a phenol concentration of less than 0.6%. The conditions were found which enable C. freundii 62 and 63 to synthesize from lactic acid tyrosine and DOPA with the yield of 35-38 g/l and 32-33 g/l, respectively.

Aerobiosis↗

Cysteine conjugate beta-lyase in the gastrointestinal bacterium Eubacterium limosum.

A cysteine conjugate beta-lyase (beta-lyase) from the gastrointestinal bacterium Eubacterium limosum has been isolated and characterized. This organism has the highest specific activity for cysteine conjugate beta-lyase of the gastrointestinal bacteria studied. The beta-lyase was found to cleave the thioether linkage of S-alkyl- and S-aryl-L-cysteine conjugates. Stoichiometric amounts of 2-mercaptobenzothiazole, pyruvic acid, and ammonia were produced from the beta-lyase cleavage of S-(2-benzothiazolyl)-L-cysteine. The enzyme activity was inhibited by hydroxylamine, iodoacetic acid, or KCN. The enzyme appears to be a 75,000-Da dimer of two 38,000-Da subunits. A natural substrate, cystathionine, was cleaved by this enzyme, indicating that this beta-lyase has beta-cystathionase activity. These data suggest that a beta-cystathionase from E. limosum may be an important enzyme in the metabolism of a wide range of cysteine conjugates of xenobiotics to thiol-containing products.

Animals↗

Fast hemoglobins and red blood cell metabolites in citrate phosphate dextrose adenine stored blood.

Blood was drawn from 10 fasted, healthy volunteers and stored under standard blood bank conditions in citrate-phosphate-dextrose-adenine (CPDA-1). Blood was sampled before storage (Day 0) and on Days 5, 12, 19, 26, and 35. Laboratory testing for glucose, HbAla + b, HbAlc, pyruvic acid, lactic acid, adenosine triphosphate (ATP), 2, 3-diphosphoglycerate (2,3DPG), plasma free hemoglobin (Hb) and pH (blood gases) were performed. In addition, P50 was also serially measured in two of the individuals and in their stored blood. Significant elevations of HbAla + b and HbAlc (fast hemoglobins) were found on Days 12 and 19 of storage (p less than 0.05). These elevations of fast hemoglobins are due to hypoxia, acidosis, and hyperglycemia. Following the initial elevation of the fast hemoglobins (Hbs), there was a decline in their concentration, from Day 12, which could partly be explained by cell death.

Adenine↗

[Pathogenic role of O. venulosum in lambs].

Studied was the effect of an experimental infection of lambs with 1000 and 4000 larvae of Oesophagostomum venulosum on the activity of some more important serum enzymes, the level of sulfhydryl groups, and the level of sugar. It was found that the activity of glutamic acid oxal-acetate transaminase and lactic acid dehydrogenase rose, and that of alkaline phosphatase dropped. At 4000 larvae the level of glutamic acid pyruvate transaminase rose. The concentration of blood sugar dropped. There was also a drop of the SH groups. It was best manifested from the first to the third week following infection. In the fourth week the level of the total and residual SH groups showed a trend toward coming back to normal, however, the initial values were not reached.

Alanine Transaminase↗

Central and cerebral hemodynamics and metabolism of the healthy man during head-down tilting.

Experiments on six healthy test volunteers, who underwent simultaneous catheterization of different cardiovascular compartments, were carried out to study the effect of head-down tilting at an angle of -20 degrees on the central and cerebral hemodynamics and metabolism. By the third hour of exposure, the test subjects showed a decrease in the systolic arterial pressure and increases in the systolic pressure of the right ventricle, heart rate, cardiac output, and oxygen intake. They also displayed a trend for an increase in the content of adenosine triphosphate, a decrease in the content of pyruvic acid, and essentially no changes in the concentration of lactic acid and activity of lactate dehydrogenase in the arterial blood and in the blood flowing out from the brain. The oxygen arteriovenous difference for the systemic and cerebral circulation decreased by 24% and 13%, respectively. The above circulatory and metabolic changes seem to reflect processes of adaptation of the human body to functioning under conditions of cephalad fluid shifts.

Acid-Base Equilibrium↗

The biosynthesis of cyanogenic glucosides in higher plants. N-Hydroxytyrosine as an intermediate in the biosynthesis of dhurrin by Sorghum bicolor (Linn) Moench.

The following compounds were tested as early intermediates in the conversion of tyrosine to p-hydroxymandelonitrile by a microsomal preparation from dark grown sorghum seedlings: p-hydroxyphenylacetamide, 1-nitro-2-p-hydroxyphenylethane, p-hydroxyphenyl-pyruvic acid oxime, tyramine, N-hydroxytyramine, and N-hydroxytyrosine. Of these, only N-hydroxytyrosine was metabolized to p-hydroxymandelonitrile. N-Hydroxytyrosine was produced from L-[U-14C]tyrosine in tracer experiments when unlabeled N-hydroxytyrosine was added as a trap. These data indicate N-hydroxytyrosine as the first intermediate in the biosynthesis of dhurrin, the cyanogenic glucoside of sorghum, and represent the first demonstration of the formation of an alpha-N-hydroxy-amino acid in a biological system. The enzyme system involved in this reaction was partially characterized with respect to substrate specificity and the effect of various inhibitors. The enzyme was shown to have properties different than those reported for the mammalian enzyme system(s) involved in the N-hydroxylation of amine drugs. The possible involvement of N-hydroxyamino acids in the biosynthesis of other secondary plant products is discussed.

Glucosides↗

Clinical, enzymological and histological changes in chronic diffuse liver diseases following (+)-cyanidanol-3 (Catergen) treatment.

The effect of (+)-cyanidanol-3 (Catergen) monotherapy was examined in 18 patients with alcoholic liver disease and in 12 patients with chronic active hepatitis. During the administration of the drug the majority of complaints diminished or ceased in both groups. In patients with alcoholic liver disease bromsulphalein retention and gamma glutamyl transferase levels decreased, in chronic active hepatitis serum glutaminic pyruvic acid transaminase (SGPT) and alkaline phosphatase levels increased, pseudocholinesterase level decreased. The histological abnormalities of alcoholic liver injury improved in the majority of cases, on the other hand, it was deteriorated in two third of the cases with chronic active hepatitis. In two cases the histological recovery of acute alcoholic hepatitis was observed. On the basis of this results we conclude that Catergen has an excellent therapeutic effect in alcoholic liver injury while in chronic active liver diseases it can be applied only as a part of combined therapy.

Adult↗

[Effect of protein-markers of growth on oxidative phosphorylation in mitochondria].

Growth marker proteins (GMP) were studied for their effect on oxidative phosphorylation in the heart and liver mitochondria of rabbits. It is shown that GMP decrease a respiratory control (RC) coefficient, P/O coefficient, inhibit respiration of the mitochondria in metabolic states 3, 5 and activates it in state 4. The nature of the oxidation substrates (FAD- and NAD-dependent succinic and pyruvic acids, respectively) does not influence the GMP effect manifestation. It is supposed that GMP disturb the structural and functional integrity of the mitochondria. Variations in bioenergetic parameters of the heart and liver mitochondria in organisms with active growth foci as well as of mitochondria incubated with GMP, are unidirectional. Cytochrome c, coenzyme A (Co ASH) and other thyol compounds (cystein, dithiotreitol, glutathione--GSH) remove the GMP action.

Animals↗

Special bacterial polysaccharides and polysaccharases.

Alcaligenes faecalis var. myxogenes 10C3, which we isolated from soil, produces a water-soluble and an insoluble extracellular polysaccharide. The former (succinoglycan) is composed of glucose, galactose, pyruvic acid and succinic acid (molar proportions 7:1:1:1) with (beta 1-3)-, (beta 1-4)- and (beta 1-6)-glucosidic linkages. The latter (curdlan) is composed entirely of (beta 1-3)-linked D-glucose and forms a resilient firm gel when heated in suspension. The organism also produces extracellularly a repeating-unit octasaccharide of succinoglycan and cyclic (beta 1-2)-D-glucan. These polymers or oligomers are also produced by many strains of Agrobacterium and Rhizobium. Spontaneous mutation in ability to produce these polysaccharides or oligosaccharides occurs in these strains. The structures of succinoglycan, and similar polymers containing riburonic acid or galactose as the end residue of the side chain, were elucidated by successive fragmentation with two special enzymes obtained from Cytophaga arvensicola followed by methylation analysis. It is interesting that the unit compound in the biosynthesis of succinoglycan is identical with the unit compound in the enzymic decomposition of the polymer. Studies on curdlan gel by X-ray, 13C n.m.r. and electron-microscopic analysis and other physicochemical methods showed that the molecular structure of curdlan changes from a single helix to a triple stranded helix on heat treatment at high temperature. Curdlan seems to be useful for making new types of jelly products and may also be useful in new procedures for food production. Interestingly, curdlan possesses marked antitumour activity. Extracellular isoamylase (EC 3.2.1.68; glycogen 6-glucanohydrolase) of Pseudomonas amyloderamosa SB 15, which we isolated from soil, is very useful for elucidation of the structure of amylopectin and glycogen, and also for the commercial production of amylose or maltose alone or in combination with beta-amylase. Maltose is useful as a sugar for injection, being better than glucose. Maltitol is easily produced from maltose by chemical reduction and is used as a low-calorie sweetener. The isoamylase is also effective for enhancing the production of glucose from starch by the action of glucoamylase.

Alcaligenes↗

[Cerebrocortical necrosis in calves, sheep and goats].

Cerebrocortical necrosis was induced through the oral application of amprolium to calves (0.250 g/kg to 1.00 g/kg) and weaned lambs and goats (1.25 g/kg) in the course of 25 to 35 days. In order to shed light on the etiology of the disease an experiment was carried out with a ration rich in carbohydrates for calves and sheep. Clinically, the disease was manifested with nervous symptoms. Biochemically, a drop of the amount of B1 in the blood serum, liver, and brain was established, along with a rise of pyruvic acid in the blood serum. Morphologically, most characteristic were the laminar necroses, the domination colliquative processes that led to deformation, and the atrophy of the folds of the brain cortex. Analogous changes were found also in the investigation of the spontaneously affected calves and lambs originating from different farms.

Animals↗

Lactic acid concentrations in vitreous humor: their use in asphyxial deaths in children.

Lactic acid concentrations in brain tissue of humans have been shown to increase with an extended agonal period. Infants and children dying from various causes are undergoing different stress conditions terminally and the postulate of this study is that natural death cases and traumatic asphyxia cases are characterized by varying agonal periods, the former being somewhat prolonged with the latter being rather brief. One-hundred-and-two cases of infants and children were examined for vitreous humor lactic acid concentrations. They were divided into two major categories, Sudden Infant Death Syndrome (SIDS) and non-SIDS cases. SIDS was further divided into SIDS without additional findings and SIDS with secondary findings which contributed to death. The non-SIDS category included traumatic asphyxia cases as well as those dying from blunt trauma, known respiratory diseases, and other causes. Categorical mean values and standard deviations were calculated. The vitreous humor lactic acid mean value for traumatic asphyxia was significantly lower than the mean value for SIDS. Also the mean value for known respiratory diseases was statistically lower than the mean value for SIDS with secondary findings. These findings are probably suggestive of agonal time differences and may be a reflection of the various mechanisms of death.

Asphyxia↗

[Mechanism of the cardiotoxic effect of various industrial poisons (metals)].

The effect of acute and repeated action of cobalt, lead, antimony on the metabolism of the heart muscle is shown. High doses of the metals of approximately 1/5 LD50 were studied in the acute experiment and doses one fifth these in the repeated experiment. The data obtained indicated that due to the effect of all the poisons studied changes developed early in catecholamine metabolism - the myocardial noradrenaline content decreased and the blood and urine monamine levels rose. Increase in the content of pyruvic acid, intensification of glycogenolysis processes (increase in phosphorylase a activity and decrease in the glycogen level), and diminished activity of lactate dehydrogenase in the myocardium attested to changes in its metabolism. High doses of the metals caused an increase in the free activity of the lysosome enzymes, cathepsins and of acid phosphatase, which indicated that the permeability of the membranes of these organelles was disturbed. The mechanism of the cardiotoxic effect of the metals is discussed.

Acid Phosphatase↗

[Effect of Krebs cycle intermediates on the blood supply and energy metabolism of ischemic myocardium].

The influence of d-ketoglutarate and succinate in acute experiments on dogs was studied by the following parameters: collateral coronary circulation (CCC) of the ischemic myocardium, systemic arterial pressure, and the content of lactic, pyruvic acids, and glucose in the blood flowing from the ischemic zone. alpha-ketoglutarate (6 mg/kg intracoronary and 60 mg/kg intravenously) proved to produce a positive effect on CCC and the contractile activity of the myocardium. Intravenous injection of alpha-ketoglutarate (12 mg/kg) and succinate (100 mg/kg) decreased significantly the consumption of glucose by the ischemic myocardium which rose after the ligation. In comparison with alpha-ketoglutarate, all doses of succinate were more effective as a factor of preventing the increase of lactic acid in the blood flowing from the ischemic zone. Thus, definite doses of alpha-ketoglutarate and succinate could be used for pharmacological correction of CCC and energy supply of the ischemic myocardium.

Acute Disease↗

The enzymatic synthesis of sepiapterin by chicken kidney preparations.

A chicken kidney preparation which catalyzes the conversion of D-erythro-dihydroneopterin triphosphate to dihydrobiopterin in the presences of Mg2+ and NADPH has been fractionated into three fractions, A2, A1, and B. Fraction A2 in the presence of Mg2+ catalyzes the conversion of D-erythro-dihydroneopterin triphosphate to an unknown intermediate designated compound X. Fraction A1 in the presence of NADPH catalyzes the conversion of compound X to sepiapterin. Fraction B, in the presence of NADPH, catalyzes the conversion of sepiapterin to dihydrobiopterin. Fraction B which is sepiapterin reductase was not studied any further. Fraction A1 is heat-labile and its molecular weight is estimated to be 3.0 x 10(4), whereas fraction A2 is heat-stable and its molecular weight, 7.7 x 10(4). Compound X is labile and its degradation products have been identified to be pterin and pyruvic acid. This information suggests that compound X is 6-(1,2-dioxopropyl)-7,8-dihydropterin.

Alcohol Oxidoreductases↗