[Reduced glutathione interaction with thiophosphoric derivatives of alkaloids of Chelidonium majus L. in vitro].

The interaction between reduced glutathione and thiophosphoric derivatives of alkaloids of greater celandine was studied by the photometric method of analysis and fluorescence spectroscopy in vitro. Results demonstrate possibility of specific interaction between reduced glutathione and thiophosphoric derivatives of alkaloids. It is possible that similar interaction of thiophosphoric derivatives of alkaloids may involve SH-groups of amino-acid residues, at the active sites of some metabolic enzymes.

[Changes in amino acid patterns of blood plasma in tumor patients treated with anticancer drug NSC-631570: possible approaches to cancer diagnostics].

In our early experimental (with W-256, SM-1 and PC-1 tumors) and clinical (breast, bladder and prostate cancers) studies the use of the anticancer drug NSC-631570 was proven to be safe and highly effective, inhibiting protein synthesis in cancer cells, selectively accumulating in cancer tissue after a single intravenous administration and controlling cancer-induced metabolic imbalance. This drug inhibits metabolic processes in the tumor and causes metabolic disorders in cancer cells. Moreover, NSC-631570 induced the changes in certain amino acids concentrations in biological fluids and tumor tissue in animal models and cancer patients. These changes cannot be explained by metabolic amino acid disorders in cancer known so far. In this study the effects of NSC-631570 on blood plasma amino acids has been investigated. Blood was sampled from 10 healthy donors and 29 patients with different types of cancer (stomach, rectal, lung, breast, bladder, prostate, and leukemia). Comparison of NSC-531570 effects in plasma of healthy donors and cancer patients has shown, that this compoumd: 1) affects amino acids with positively charged (His, Arg) or not charged (Tyr, Thr, Gln) R-groups; 2) decreases concentration of His and increase the concentrations of beta-Ala and Tau. These changes depend on the concentration of NSC-631570 and the type of cancer. On the basis of the literature data and the results of our studies we suggest that Ukrain's biological actions in cancer are realized at least partly through selective interaction with amino acids, their derivatives, and plasma proteins. These data provide the background for the using Ukrain in the cancer detection and investigating the mechanisms of carcinogenesis.

[Biochemical basis of valproic acid toxicity: role of oxidative stress and effects of L-carnitine]. / Biokhimicheskie osnovy toksichnosti val'proevoi kisloty: rol' okislitel'nogo stressa i éffekty L-karnitina.

Reduced hepatic mitochondrial beta-oxidation and changes in L-carnitine metabolism are important biochemical manifestations of valproate (VA)-induced hepatic toxicity. Lipid peroxidation activation as a possible mechanism implicated in VA-induced damage as well as the possibility of L-carnitine (LC) attenuation of lipid peroxidation activity were studied. The level of malondialdehyde (MDA), lipid peroxide concentration and antioxidant activity (AOA), catalase activity, free S-S groups content in plasma and liver homogenates from male albino rats supplemented with VA (200 mg/kg, 8 days) and VA plus LC (100 mg/kg, 8 days) were measured. There were insignificant differences in MDA formation and catalase activity in the plasma and liver of control and VA-treated groups, however decreases in the plasma AOA activity and S-S groups level were observed in VA-treated rats. The LC administration significantly decreased liver lipid peroxide concentration and increased plasma AOA activity and S-S groups. Our results suggest that lipid peroxidation may be involved as an additional mechanism for VA-induced liver damage in rats. The potential antioxidant activity of LC may be particularly relevant in understanding the pharmacological and biochemical properties of LC in VA-induced pathologic conditions.

[Taurine induces an imbalance in the pool of neuroactive amino acids and biogenic amines in regions of the brain]. / Taurin indutsiruet disbalans pula neiroaktivnykh aminokislot i biogennykh aminov v otdelakh golovnogo mozga.

The paper deals with the consequences of exogenous taurine (Tau) administration (650 mg/kg, i.p., singly, for 30 min) and possible mechanisms of this compound participation in the formation of the structure of the neuroactive amino acid pool, biogenic amines and their metabolites in the hypothalamus (H), basal ganglia (BG) and cerebellum (C) of the brain of male rats weighing 160-280 g. The concentrations of amino acids as OPA derivatives were determined by reverse-phase HPLC and the content of biogenic amines and their metabolites--by ion-pair HPLC-ECD. The Tau load was followed by an elevation of the concentrations of glutamate, aspartate and their amides, GABA and tyrosine concentrations in cerebellum whereas in basal ganglia that of tyrosine and dopamine. The tryptophan, beta-alanine, dioxyphenylacetic acid, dopamine and norepinephrine levels were diminished in hypothalamus. The metabolic and functional relationships governing the imbalance of the neuroactive amino acid and biogenic amine pool in the neuroactive amino acid and biogenic amine pool in the CNS occurring after the Tau administration in vivo are interpreted using statistical analysis.

[The amino acid pool of the liver during activation of glutathione synthesis]. / Aminokislotnyi fond pecheni na fone aktivatsii sinteza glutationa.

Regularities of formation of a pool of free amino acids and their derivatives in the liver of rats were studied during L-2-oxothiazoidin-4-carboxylate-induced glutathione synthesis activation. It was shown that an increase in concentrations of sulfur-containing (cysteate, cysteine) and branched-chain (valine, isoleucine, leucine) amino acids was the most typical change. The correlation and linear-discriminant analysis of the whole range of the compounds studied in the dynamics of the experimental process has proved high informativeness of glycogenic amino acid levels, activation of the whole chain of synthesis and degradation of thiol-containing amino acids as well as determination of the obtained shifts in concentrations of reduced glutathione.

[The amino acid background of patients with obstructive jaundice before and after the surgical removal of the obstacle to bile outflow]. / Aminokislotnyi fond u bol'nykh s obturatsionnoi zheltukhoi do i posle operativnogo ustraneniia prepiatstviia ottoku zhelchi.

The amino acid pool of blood plasma, liver and bile was examined before and after operative elimination of biliary hypertension cause. The blood plasma concentration of the majority of free amino acids (especially the sulfur-containing and big neutral) before operation at cholestasis is increased in comparison with donors. For the bile outflow normalization after operation the most informative is the content in liver, blood plasma and bile of taurine, glycine and the amino acids metabolically associated with them.

[Informative value of amino acid reserve in the blood plasma in cholestatic and septic syndrome]. / Informativnost aminokislotnogo pula plazmy krovi pri sindrome kholestaza i sepsise.

Syndrome of cholestasis is characterized by pronounced increase in concentration of the sulphur containing, ketogenic amino acids and intermediates of a cycle of urea formation in the blood plasma; sepsis--by decrease in pool of glycogenic amino acids, increase in concentration of free ammonium and reduction in correlation of amino acid concentration with branched hydrocarbon chain of aromatic amino acids. In cholestasis, the levels of ammonium alpha-amino butyrate and aromatic amino acids were the most informative indices, in sepsis--content of lysin, glutamate, cystein and cysteate.

[Changes in the amino acid spectrum of the blood in patients with sepsis in the process of complex intensive therapy]. / Izmeneniia aminokislotnogo spektra krovi bol'nykh sepsisom v protsesse kompleksnoi intensivnoi terapii.

Amino acid fund has been studied during complex therapy of 25 patients with sepsis. In 15 patients complex therapy included detoxicating hemosorption (3-5 sessions), in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions). Complex therapy employing hemosorption led to a decrease in serine plasma level. Changes in the amino acid fund of the whole blood were insignificant. Leucine, isoleucine, threonine and phenylalanine blood levels were significantly increased. The introduction of ultraviolet blood irradiation into complex therapy of patients reduced traumatic effect of sorption detoxication on blood cells and enhanced detoxicating effect.

[Relations between plasma amino acid metabolism and the functional state of the liver in inflammatory diseases of the gallbladder]. / Sviaz' obmena aminokislot plazmy krovi i funktsional'nogo sostoianiia pecheni pri vospalitel'nykh zabolevaniiakh zhelchnogo puzyria.

In 70 patients with acute and chronic cholecystitis, a change in content of free amino acids in the blood, which confirms involvement of the liver into a pathologic process, is noted. Operative intervention aggravates metabolic disorders. By day 7-10 after the operation, the amino acid disbalance more pronounced in chronic course of the disease retains.

[Changes in the amino acid spectrum pf the blood in patients with sepsis undergoing complex intensive therapy]. / Izmeneniia aminokislotnogo spektra krovi bol'nykh sepsisom v protsesse kompleksnoi intensivnoi terapii.

Amino acid fund was studied during intensive therapy of 25 patients with sepsis. In 15 patients complex therapy involved detoxicating hemosorption (3-5 sessions) and in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions). Complex therapy with hemosorption led to a decrease in plasma serine content. The amino acid fund of the whole blood changed insignificantly. There was a significant increase in leucine, isoleucine, threonine and phenylalanine levels. The introduction of ultraviolet blood irradiation into complex therapy of patients decreases a traumatic effect of sorption detoxication on blood cells and potentiates detoxicating effect.

[The free amino acid content of the blood serum in bladder cancer patients]. / Soderzhanie svobodnykh aminokislot v syvorotke krovi bol'nykh rakom mochevogo puzyria.

The content of 18 amino acids in the blood serum was studied in 57 patients with T2-4 carcinoma of the bladder according to the stage of the process and the functional condition of the kidneys. Dysaminoacidemia was found in patients with T2 bladder carcinoma, which did not need correction; marked hypoaminoacidemia was encountered in stage T3-4 tumors. Chronic renal insufficiency (intermittent and terminal stages) is conductive to significant decrease of the blood amino acid level. The content of amino acids is lower in the postoperative than in the preoperative period. The degree of reduction of the amino acid content in blood was found to be dependent on the volume of the operation. The reduction of the amino acid content is more intense after cystectomy than after resection of the bladder. Correction of the blood amino acid content in the preoperative period in patients with T3-4 carcinoma of the bladder reduces the incidence of postoperative complications. Correction of hypoaminoacidemia with polyamine proves effective in patients with maintained renal nitrogen excreting function. In development of azotemia in patients with bladder carcinoma, substitution transfusion therapy for correction of hypoaminoacidemia becomes effective only after restoration of the nitrogen excreting function of the kidneys.

[Formation of free fatty acid pool in the liver of rats during starvation]. / Formirovanie fonda svobodnykh aminokislot pecheni krys v dinamike golodaniia.

Absolute starvation during 2 days induces increased levels of taurine, phosphoethanolamine, ethanolamine, glycine, serine, threonine and decreased levels of aspartate, lysine, methionine and cystine in the rat liver. The ration of nonessential to essential, and glycogenic to ketogenic amino acids increased on the average by 30%. On day 4 of starvation the level of nonessential glycogenic amino acids is significantly lowered, while the concentration of essential ketogenic amino acids is increased. On day 6 essential ketogenic amino acid pool is more increased. On day 10 the shifts in the amino acid pool in the liver are retained, the reduction of alanine and serine content is most typical. The value of D2-Machalanobis, obtained during lineal discriminant analysis of amino acid pool and space distribution of the signs for the control and starving animals (during 10 days), was lower than that on day 4 and 6 of the experiment. The levels of glycine, serine lysine, leucine, glutamate, alanine and aspartate show the highest information content during such investigation of all the groups of animals.

[Free amino acids of the liver and the characteristics of the amino acid metabolism in the liver and brain after cyanamide administration to rats]. / Svobodnye aminokisloty pecheni i osobennosti obmena aminokislot pecheni i mozga pri vvedenii tsiamida krysam.

A single administration to rats of cyanamide (60 mg/kg, for 1 hour) was found to decrease the contents of cysteate, serine, glutamate, glycine, alanine, valine, methionine, isoleucine, tyrosine, ethanolamine, ornithine and histidine that may be considered as a manifestation on the drug hepatotoxicity. The activities of transaminases, glutamate dehydrogenase, pyruvate dehydrogenase remained unchanged. Cyanamide effects were considerably abolished by the supplementary ethanol administration (0.5 g/kg). Cyanamide failed to affect vitamin-dependent enzymes reflecting thiamine pyrophosphate, pyridoxal phosphate and flavine adenine dinucleotide status of the rat organism.

[Changes in protein metabolism and the free amino acid profile in bladder cancer]. / Izmeneniia belkovogo obmena i fond svobodnykh aminokislot pri rake mochevogo puzyria.

Protein metabolism status was assessed by standard procedures versus tumor stage and nitrogen-excreting function of the kidneys in 250 cases of urinary bladder cancer. In addition, 18 amino acids in the blood were assayed in 63 patients. Standard methods of examination identified protein metabolism disturbances in patients with stage III-IV renal failure whereas amino acid profile showed changes at a much earlier stage. Patients with T3-4 tumors revealed decreased blood amino acid levels. Renal failure and surgical trauma caused the level of most amino acids checked to decrease. The need for correction of the amino acid profile of the blood before and after surgery is discussed.

[Formation of taurine and amino acid pools in rat tissues upon stimulation of NAD synthesis]. / Formirovanie taurinovogo pula i aminokislotnogo fonda v tkaniakh krys v usloviiakh stimuliatsii sinteza NAD.

A single intraperitoneal injection of nicotinamide (500 mg/kg) to mongrel albino rats causes a 6-hour increase in the 2-oxoglutarate level and the free NAD+/NADH ratio in liver mitochondria. The levels of taurine and taurocholates as well the activity of cysteine oxidase in liver tissues remains thereby unchanged, whereas the cysteine transaminase activity diminishes. In the heart and brain of experimental animals the activity of both enzymes is decreased. In the liver, blood plasma and heart of experimental animals, the Ala and Ser levels are low, whereas the taurine content is elevated both in blood plasma and brain. Nicotinamide administration eliminates positive correlations between the levels of taurine, its precursors and metabolically bound amino acids. In the liver the negative correlations between the activities of cysteine oxidase and cysteine transaminase observed in the control group disappear in the experimental group. Apparently, one of regulatory mechanisms of the taurine pool formation in the liver is the ratio of activities of the both enzymes as well as their competition at the substrate level. This emphasizes the importance of the transamination reactions in the metabolism of sulphur-containing amino acids.

[Characteristics of intracellular metabolism of carbohydrates and amino acids in animals with thiamine deficiency]. / Zakonomernosti vnutrikletochnogo metabolizma uglevodov i aminokislot u zhivotnykh pri nedostatochnosti tiamina.

Vitamin B1 deficiency in mongrel albino rats induced by oxythiamine is concomitant with an increase in the ratio of free forms of NAD+/NADH, NADP+/NADPH in liver mitochondria. This is accompanied with a rise in steady-state concentrations of isocitrate, 2-oxoglutarate and with a decrease of malate in liver tissue, which testifies to the prominent regulatory role of the 2-oxoglutarate dehydrogenase complex in the intracellular metabolism under vitamin B1 deficiency. Moderate physical load causes a 10-fold increase in the steady-state concentration of pyruvate and lactate in the blood of thiamine-deficient animals, which seems to be due to the stimulation of glycolysis in the maintenance of energy homeostasis. The observed increase in the excretion of pyruvate, lactate, 2-oxoglutarate (30-fold against control) and pentose phosphates (3-fold) with urine, depending on the degree of vitamin B1 deficiency, points to one of essential mechanisms of cell metabolism stabilization under the given pathological condition.

[Study of the interaction of pyridoxal-5'-phosphate and human serum albumin in the presence of copper ions by circular dichroism]. / Issledovanie vzaimodeistviia piridoksal'-5'-fosfata s syvorotochnym al'buminom cheloveka v prisutstvii ionov medi metodom krugovogo dikhroizma.

When pyridoxal-5'-phosphate (PLP) binds with human serum albumin (HSA) in the molar ratio of 1:1, negative in sign induced Cotton effect is observed in the ligand absorption band. This high affinity center is localized in the second domain at an alpha-helical site of the protein molecule. As a result of adding Cu2+ equimolar concentration a new optically active PLP binding site with the positive sign of Cotton effect is acidic medium and the opposite one in alkaline medium is formed on Lys-4 at the beginning of the polypeptide chain. Inversion of the CD spectrum occurs over the same range of pH of the medium as the change in symmetry of electric field surroundings (rhombic in equilibrium axial) of the copper ion within the equimolar ternary complex HSA: PLP: Cu2+.