Low-molecular-weight metabolites relevant to ethanol metabolism: correlation with alcohol withdrawal severity and utility for identification of alcoholics.

The blood levels of ethanol, acetaldehyde, acetate, methanol, acetone, lactate, pyruvate, and glucose were measured in 23 male alcohol-dependent patients on days 2 to 6 after hospitalization and in 22 healthy male blood donors. Correlations between the biochemical parameters and 17 symptoms of the alcohol-withdrawal syndrome (AWS) were calculated. Abnormally high levels of ethanol, methanol, acetate, and acetone as well as hypoglycaemia were found on day 2, but lactacidaemia and pyruvataemia were pronounced throughout the observation period. AWS severity correlated positively with the acetone content on day 2 and with the acetate content on days 2 to 6. Negative correlations were found between ethanol levels and craving for alcohol, methanol levels and craving for alcohol, and between psychopathologic disorders and the total AWS severity score. The results suggest that concentrations of blood ethanol, methanol, acetate, and acetone exceeding their normal endogenous levels can be used only as indicators of recent heavy drinking. Linear discriminant analysis using the levels of the nine parameters studied enabled the correct classification of 91% to 96% of alcoholic patients during 1 week of abstinence and 100% of control subjects. The most informative parameters in the discrimination between alcoholics and controls were lactate, pyruvate, the lactate/pyruvate ratio, acetate, and acetone.

[Metabolism of vitamin B1 and its di- and triphosphate esters in experimental allergic encephalomyelitis]. / Metabolizm vitamina B1 i ego di- i trifosfornogo efirov pri éksperimental'nom allergicheskom éntsefalomielite.

Biological significance of thiamin in development of experimental allergic encephalomyelitis has been elucidated. It has been shown that at the late preclinical stage of the disease thiamine metabolism is predominantly directed towards the maintaining of cellular metabolic homeostasis, whereas at the stage of clinical symptoms the anabolic process gives way to catabolic decomposition. Among tested thiamine phosphates the triphosphate ester is the most informative parameter in demyelinizing processes. Thiamine injections to immunized animals accelerate the vitamin phosphorylation depleting the reducing and energy potentials of the cell. Such thiamine antagonist as oxythiamine inhibits phosphatase reactions.

[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.

[Methods of statistical analysis in the complex evaluation of disorders of the blood levels of free amino acids in alcoholic abstinence syndrome]. / Metody statisticheskogo analiza v kompleksnoi otsenke narushenii v fonde svobodnykh aminokislot krovi pri alkogol'nom abstinentnom sindrome.

A study was made of the formation of the pool of free amino acids in patients with the alcoholic abstinence syndrome (AAS) of varying gravity as well as in the course of detoxication therapy. On admission the patients demonstrated a marked negative relationship between the levels of alpha-aminobutyric acid, serine, cystine, glutamine and the gravity of the AAS. Both mild and grave patterns of the AAS are characterized by the rise of the content of alpha-aminobutyric acid, glycine, valine, phenylalanine, ammonia and by a dramatic decline of the glutamine level. The most informative parameters determined by linear discriminant analysis in the course of detoxication therapy include alpha-aminobutyric acid, lysine, alanine and glutamine. The adequacy of the use of factor analysis for the assessment of the efficacy of a complex of therapeutic measures is discussed.

[Changes in the fatty acid composition of erythrocyte membranes in patients with chronic alcoholism under the effect of a diet enriched with linoleic acid]. / Izmeneniia zhirno-kislotnogo sostava membran éritrotsitov u bol'nykh khronicheskim alkogolizmom pod vliianiem ratsiona, obogashchennogo linolevoi kislotoi.

The authors have studied the influence of additional introduction into the ration of sunflower oil on fatty-acid composition of erythrocytic membranes in chronic alcoholics. The computerized discriminant analysis has evidenced that additional introduction of sunflower oil into the ration of the patients normalizes the fatty-acid spectrum of erythrocytic membranes. Besides that, enrichment of the ration with linoleic acid improves the parameters characterizing the liver function (bilirubin, alanine aminotransferase of blood serum).

[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.

[Interaction of pyridoxal-5-phosphate with human serum albumin and pancreatic ribonuclease]. / Vzaimodeistvie piridoksal'-5-fosfata s syvorotochnym al'buminom cheloveka i pankreaticheskoi ribonukleazoi.

Pyridoxal-5-phosphate (in a lesser degree, pyridoxal) interacts with both non-protonated and protonated exposed epsilon-amino groups of lysine residues and with alpha-amino groups in human serum albumin and pancreatic ribonuclease A. The reaction of Schiff base formation proceeds within a wide pH range--from 3.0 to 12.0. At a great pyridoxal-5-phosphate excess in ribonuclease A in neutral or slightly acidic aqueous media all the ten epsilon-amino groups of lysine residues and the alpha-amino groups of Lys-1 become modified. The formation of aldimine bonds of pyridoxal-5-phosphate with protonated amino groups in acidic media is determined by ionization of its phenol hydroxyl and phosphate residues. Acetaldehyde, propionic aldehyde and pyridine aldehyde interact only with non-protonated amino groups of the proteins. The equilibrium constants of pyridoxal-5-phosphate and other aldehydes binding to proteins and amino acids were determined. The rate constants of Schiff base formation for pyridoxal-5-phosphates with some amino acids and primary sites of proteins for direct and reverse reactions were calculated.

[Deuterium exchange of the methyl group of pyruvate catalyzed by human serum albumin]. / Issledovanie deiteroobmena metil'noi gruppy piruvata, kataliziruemogo syvorotochnym al'buminom cheloveka.

Human serum albumin catalyzes proton exchange of the methyl group of the pyruvate molecule in heavy water. The exchange process is mainly due to the formation of bonds of a Schiff base type between six deprotonated protein amino groups and pyruvate. Both hydrated and non-hydrated forms of pyruvate interact with positively charged side amino acid residues of the polypeptide chain (most probably, with arginine) located in the hydrophobic "pockets" of the protein globule. The value of equilibrium association constants with serum albumin exceeds that for the hydrated form of pyruvate.