The effect of ß-alanine supplementation on high intensity cycling capacity in normoxia and hypoxia.

The availability of dietary beta-alanine (BA) is the limiting factor in carnosine synthesis within human muscle due to its low intramuscular concentration and substrate affinity. Carnosine can accept hydrogen ions (H+), making it an important intramuscular buffer against exercise-induced acidosis. Metabolite accumulation rate increases when exercising in hypoxic conditions, thus an increased carnosine concentration could attenuate H+ build-up when exercising in hypoxic conditions. This study examined the effects of BA supplementation on high intensity cycling capacity in normoxia and hypoxia. In a double-blind design, nineteen males were matched into a BA group (n = 10; 6.4 g·d-1) or a placebo group (PLA; n = 9) and supplemented for 28 days, carrying out two pre- and two post-supplementation cycling capacity trials at 110% of powermax, one in normoxia and one in hypoxia (15.5% O2). Hypoxia led to a 9.1% reduction in exercise capacity, but BA supplementation had no significant effect on exercise capacity in normoxia or hypoxia (P > 0.05). Blood lactate accumulation showed a significant trial x time interaction post-supplementation (P = 0.016), although this was not significantly different between groups. BA supplementation did not increase high intensity cycling capacity in normoxia, nor did it improve cycling capacity in hypoxia even though exercise capacity was reduced under hypoxic conditions.

Dietary GABA induces endogenous synthesis of a novel imidazole peptide homocarnosine in mouse skeletal muscles.

Carnosine (ß-alanyl-L-histidine) is an imidazole dipeptide present at high concentrations in skeletal muscles, where it plays a beneficial role. However, oral intake of carnosine or ß-alanine to increase skeletal muscle carnosine levels has disadvantages such as low efficiency and side effects. Therefore, we proposed homocarnosine (γ-aminobutyryl-L-histidine) as a novel alternative imidazole peptide for skeletal muscle based on its structural similarity to carnosine. To induce endogenous homocarnosine synthesis in skeletal muscles, mice were fed a basal diet mixed with 0, 0.5, 2, or 5% γ-aminobutyric acid (GABA) for 6 weeks. As expected, in the control group (0% GABA), GABA and homocarnosine were present in trace concentrations. Skeletal muscle homocarnosine levels were significantly increased in the 2% and 5% GABA intake groups (tenfold, P < 0.01 and 53-fold, P < 0.01; respectively) relative to those of the control group, whereas 0.5% GABA intake induced no such effect. GABA intake had no effect on the levels of carnosine, anserine, and ß-alanine. Vigabatrin (inhibitor of GABA transaminase (GABA-T)) administration to mice receiving 2% GABA intake for 2 weeks led to GABA-T inhibition in the liver. Subsequently, a 43-fold increase in circulating GABA levels and a tendency increase in skeletal muscle homocarnosine levels were observed. Therefore, skeletal muscle homocarnosine synthesis can be induced by supplying its substrate GABA in tissues. As GABA availability is tightly regulated by GABA-T via GABA degradation, inhibitors of GABA or ß-alanine degradation could be novel potential interventions for increasing skeletal muscle imidazole dipeptides.

A kinetic model of carnosine synthesis in human skeletal muscle.

Drawing on previously published data, a mathematical model is proposed to describe the synthesis of carnosine in muscle using a slow release ß-alanine supplement (SR-CarnoSyn®). The model pre-supposes that the rate of synthesis for any given dose of ß-alanine (within the range 1.6-6.4 g day-1) is constant with time, but is first order with respect to daily ß-alanine dose. Simultaneously with synthesis, decay in carnosine is also assumed to be occurring, the rate in this case being a function of the concentration of carnosine. Decay in carnosine appears describable by first-order kinetics. By integration of the two rate reactions, a single mathematical equation was derived to describe the synthesis of carnosine and which closely fitted the experimental data over 56 days. The model, if validated by additional studies, could be used to compliment empirical observations of the changes in carnosine in muscle with supplementation, and allow objective examination of a number of possible influences affecting the rate constants of synthesis and decay.

Comparison of sustained-release and rapid-release ß-alanine formulations on changes in skeletal muscle carnosine and histidine content and isometric performance following a muscle-damaging protocol.

ß-alanine supplementation increases muscle carnosine content and improves anaerobic exercise performance by enhancing intracellular buffering capacity. ß-alanine ingestion in its traditional rapid-release formulation (RR) is associated with the symptoms of paresthesia. A sustained-release formulation (SR) of ß-alanine has been shown to circumvent paresthesia and extend the period of supply to muscle for carnosine synthesis. The purpose of this investigation was to compare 28 days of SR and RR formulations of ß-alanine (6 g day-1) on changes in carnosine content of the vastus lateralis and muscle fatigue. Thirty-nine recreationally active men and women were assigned to one of the three groups: SR, RR, or placebo (PLA). Participants supplementing with SR and RR formulations increased muscle carnosine content by 50.1% (3.87 mmol kg-1ww) and 37.9% (2.62 mmol kg-1ww), respectively. The change in muscle carnosine content in participants consuming SR was significantly different (p = 0.010) from those consuming PLA, but no significant difference was noted between RR and PLA (p = 0.077). Although participants ingesting SR experienced a 16.4% greater increase in muscle carnosine than RR, fatigue during maximal voluntary isometric contractions was significantly attenuated in both SR and RR compared to PLA (p = 0.002 and 0.024, respectively). Symptoms of paresthesia were significantly more frequent in RR compared to SR, the latter of which did not differ from PLA. Results of this study demonstrated that only participants consuming the SR formulation experienced a significant increase in muscle carnosine. Differences in the muscle carnosine response between these formulations may have practical significance for athletic populations in which small changes may have important implications on performance.

Optimizing human in vivo dosing and delivery of ß-alanine supplements for muscle carnosine synthesis.

Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic ß-alanine (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n=8), there is a significant linear correlation between total grams of BA consumed (of daily intake ranges of 1.6-6.4 g BA/day) versus both the relative and absolute increases in muscle carnosine. Supporting this, a recent dose-response study demonstrated a large linear dependency (R2=0.921) based on the total grams of BA consumed over 8 weeks. The pre-supplementation baseline carnosine or individual subjects' body weight (from 65 to 90 kg) does not appear to impact on subsequent carnosine synthesis from BA consumption. Once muscle carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow-release BA tablet supplement has been developed showing a smaller peak plasma BA concentration and delayed time to peak, with no difference in the area under the curve compared to pure BA in solution. Further, this slow-release profile resulted in a reduced urinary BA loss and improved retention, while at the same time, eliciting minimal paraesthesia symptoms. However, our complete understanding of optimizing in vivo delivery and dosing of BA is still in its infancy. Thus, this review will clarify our current knowledge of BA supplementation to augment muscle carnosine as well as highlight future research questions on the regulatory points of control for muscle carnosine synthesis.

Effect of two ß-alanine dosing protocols on muscle carnosine synthesis and washout.

Carnosine (ß-alanyl-L-histidine) is found in high concentrations in skeletal muscle and chronic ß-alanine (BA) supplementation can increase carnosine content. This placebo-controlled, double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout, leading to a BA dose-response study with serial muscle carnosine assessments throughout. Thirty-one young males were randomized into three BA dosing groups: (1) high-low: 3.2 g BA/day for 4 weeks, followed by 1.6 g BA/day for 4 weeks; (2) low-low: 1.6 g BA/day for 8 weeks; and (3) placebo. Muscle carnosine in tibialis-anterior (TA) and gastrocnemius (GA) muscles was measured by 1H-MRS at weeks 0, 2, 4, 8, 12 and 16. Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group. During the first 4 weeks, the increase for high-low (TA 2.04 mmol/kgww, GA 1.75 mmol/kgww) was ~twofold greater than low-low (TA 1.12 mmol/kgww, GA 0.80 mmol/kgww). 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores (week 4-8, high-low regime). The dose-response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA, which was only dependent upon the total accumulated BA consumed (within a daily intake range of 1.6-3.2 g BA/day). Washout rates were gradual (0.18 mmol/kgww and 0.43 mmol/kgww/week; ~2%/week). In summary, the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine, the muscle type, or the daily amount of supplemented BA.

Ecofriendly Synthesis of l-Carnosine in Metabolically Engineered Corynebacterium glutamicum by Reinforcing Precursor Accumulation.

Biobased processes to minimize environmental pollutants have attracted much attention. l-Carnosine has been produced by chemical synthesis, and as an alternative to this method, we newly developed engineered Corynebacterium glutamicum synthesizing l-carnosine. To develop the strain, the pentose phosphate pathway (PPP) was enhanced by attenuating flux to nonoxidative PPP. Enhanced PPP strengthened the histidine pathway and produced 5.0 g/L l-histidine and 3.9 mg/L l-carnosine. Then, the histidine synthetic pathway was reinforced by overexpressing HisG and Rel. This pathway reduced feedback inhibition by l-histidine and strengthened the flux of the histidine pathway; thus, it produced 552.20 mg/g DCW l-histidine. As a result, enhancement of the PPP accumulates more l-histidine than the histidine pathway; thus, the PPP was further enhanced by pgi gene alteration. For sufficient ß-alanine products, PanD was overexpressed and produced 99.17 mg/L l-carnosine. The final strain, Car15, which consolidated all three pathways, produced 323.26 mg/L l-carnosine via fed-batch fermentation. Finally, we confirmed the antioxidant and antiglycation effects of biologically synthesized l-carnosine, and the biologically synthesized l-carnosine showed inhibitory activity similar to that of commercial l-carnosine. Consequently, this study suggested a new biosynthetic process for l-carnosine and showed potential as a treatment for metabolic disorders through the assessment of its functions.

Synthesis of functional dipeptide carnosine from nonprotected amino acids using carnosinase-displaying yeast cells.

Carnosine (beta-alanyl-L-histidine) is one of the bioactive dipeptides and has antioxidant, antiglycation, and cytoplasmic buffering properties. In this study, to synthesize carnosine from nonprotected amino acids as substrates, we cloned the carnosinase (CN1) gene and constructed a whole-cell biocatalyst displaying CN1 on the yeast cell surface with alpha-agglutinin as the anchor protein. The display of CN1 was confirmed by immunofluorescent labeling, and CN1-displaying yeast cells showed hydrolytic activity for carnosine. When carnosine was synthesized by the reverse reaction of CN1, organic solvents were added to the reaction mixture to reduce the water content. The CN1-displaying yeast cells were lyophilized and examined for organic solvent tolerance. Results showed that the CN1-displaying yeast cells retained their original hydrolytic activity in hydrophobic organic solvents. In the hydrophobic organic solvents and hydrophobic ionic liquids, the CN1-displaying yeast cells catalyzed carnosine synthesis, and carnosine was synthesized from nonprotected amino acids in only one step. The results of this research suggest that the whole-cell biocatalyst displaying CN1 on the yeast cell surface can be used to synthesize carnosine with ease and convenience.

Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure.

Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 microM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system.

The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition.

Carnosine (Carn) occurs in high concentrations in skeletal muscle is a potent physico-chemical buffer of H+ over the physiological range. Recent research has demonstrated that 6.4 g x day(-1) of beta-alanine (beta-ala) can significantly increase skeletal muscle Carn concentrations (M-[Carn]) whilst the resultant change in buffering capacity has been shown to be paralleled by significant improvements in anaerobic and aerobic measures of exercise performance. Muscle carnosine increase has also been linked to increased work done during resistance training. Prior research has suggested that strength training may also increase M-[Carn] although this is disputed by other studies. The aim of this investigation is to assess the effect of 10 weeks resistance training on M-[Carn], and, secondly, to investigate if increased M-[Carn] brought about through beta-ala supplementation had a positive effect on training responses. Twenty-six Vietnamese sports science students completed the study. The subjects completed a 10-week resistance-training program whilst consuming 6.4 g x day(-1) of beta-ala (beta-ALG) or a matched dose of a placebo (PLG). Subjects were assessed prior to and after training for whole body strength, isokinetic force production, muscular endurance, body composition. beta-Alanine supplemented subjects increased M-[Carn] by 12.81 +/- 7.97 mmol x kg(-1) dry muscle whilst there was no change in PLG subjects. There was no significant effect of beta-ala supplementation on any of the exercise parameters measured, mass or % body fat. In conclusion, 10 weeks of resistance training alone did not change M-[Carn].

Metabolic patterns in insulin-sensitive male hypogonadism.

Male hypogonadism is a disorder characterised by low levels of the hormone testosterone. At beginning subjects with low levels of testosterone do not show insulin resistance (insulin-sensitive patients), which develops over time (insulin-resistance patients). To analyse the metabolic alterations mainly related to decreased testosterone, we performed metabolomics investigations on the plasma of males with hypogonadism who showed normal insulin levels. Plasma from patients with low testosterone (<8 nmol/l) and homeostatic model assessment for insulin-resistance-index (HOMAi) < 2.5, as well as matched controls, was analysed by UHPLC and mass spectrometry. Then metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathways. Glycolysis was not altered, as expected for the presence of insulin activity, but imbalances in several other pathways were found, such as the pentose phosphate pathway (PPP), glycerol shuttle, malate shuttle, Krebs cycle (TCA) and lipid metabolism. The PPP was significantly upregulated. Moreover, while the first steps of the Krebs cycle were downregulated, 2-oxoglutarate was replenished via glutaminolysis. Since glutaminolysis leads to an activation of the malate aspartate cycle, greater amounts of NADH and ATP with respect to the control were recorded. The activation of the glycerol shuttle was also recorded, with consequent lower triglyceride production and downregulation of beta-oxidation. This explained the moderately increased dyslipidaemia, as well as the mild increase in body mass index (BMI) observed in insulin-sensitive hypogonadism. Finally, a significant decrease in carnosine was recorded, explaining the muscle weakness commonly observed.

Biosynthesis of Carnosine and Related Dipeptides in Vertebrates.

Carnosine (ß-alanyl-L-histidine) and its methylated derivatives: anserine (ß-alanyl-Nπ- methyl-L-histidine) and balenine (ß-alanyl-Nτ-methyl-L-histidine) are abundant constituents of excitable tissues of vertebrates. While carnosine and anserine are present at high concentrations and in variable proportions in skeletal muscle and brain of most vertebrates, balenine appears to be rather more abundant in marine mammals and certain reptilian species. Since the discovery of these compounds at the beginning of 20th century, numerous studies have been devoted to identification of the biochemical and physiological properties of carnosine and related dipeptides. These led to the discovery of the pHbuffering, metal-chelation and antioxidant, capabilities of carnosine and anserine, although no definitive ideas concerning their physiological role has yet been formulated. Only recently the molecular identities of the enzymes catalyzing synthesis of carnosine (carnosine synthase, EC 6.3.2.11) and anserine (carnosine N-methyltransferase, EC 2.1.1.22) have been elucidated, which has given a new insight into their metabolism in vertebrates. These findings have opened new research areas and provide authentic opportunities for understanding the biological function of these "enigmatic" dipeptides. This review aims to summarize recent advances in our knowledge concerning enzymes responsible for the biosynthesis of carnosine and related dipeptides and to evaluate their importance in vertebrate physiology.

tan and ebony genes regulate a novel pathway for transmitter metabolism at fly photoreceptor terminals.

In Drosophila melanogaster, ebony and tan, two cuticle melanizing mutants, regulate the conjugation (ebony) of beta-alanine to dopamine or hydrolysis (tan) of the beta-alanyl conjugate to liberate dopamine. beta-alanine biosynthesis is regulated by black. ebony and tan also exert unexplained reciprocal defects in the electroretinogram, at ON and OFF transients attributable to impaired transmission at photoreceptor synapses, which liberate histamine. Compatible with this impairment, we show that both mutants have reduced histamine contents in the head, as measured by HPLC, and have correspondingly reduced numbers of synaptic vesicles in their photoreceptor terminals. Thus, the histamine phenotype is associated with sites of synaptic transmission at photoreceptors. We demonstrate that when they receive microinjections into the head, wild-type Sarcophaga bullata (in whose larger head such injections are routinely possible) rapidly (<5 sec) convert exogenous [3H]histamine into its beta-alanine conjugate, carcinine, a novel metabolite. Drosophila tan has an increased quantity of [3H]carcinine, the hydrolysis of which is blocked; ebony lacks [3H]carcinine, which it cannot synthesize. Confirming these actions, carcinine rescues the histamine phenotype of ebony, whereas beta-alanine rescues the carcinine phenotype of black;tan double mutants. The equilibrium ratio between [3H]carcinine and [3H]histamine after microinjecting wild-type Sarcophaga favors carcinine hydrolysis, increasing to only 0.5 after 30 min. Our findings help resolve a longstanding conundrum of the involvement of tan and ebony in photoreceptor function. We suggest that reversible synthesis of carcinine occurs in surrounding glia, serving to trap histamine after its release at photoreceptor synapses; subsequent hydrolysis liberates histamine for reuptake.

Carnosine, a protective, anti-ageing peptide?

Carnosine (beta-alanyl-L-histidine) has protective functions additional to anti-oxidant and free-radical scavenging roles. It extends cultured human fibroblast life-span, kills transformed cells, protects cells against aldehydes and an amyloid peptide fragment and inhibits, in vitro, protein glycation (formation of cross-links, carbonyl groups and AGEs) and DNA/protein cross-linking. Carnosine is an aldehyde scavenger, a likely lipofuscin (age pigment) precursor and possible modulator of diabetic complications, atherosclerosis and Alzheimer's disease.

In vitro study of olfactory receptor neurones expressing the dipeptide carnosine.

Olfactory neuroepithelial (OE) cells were dissociated from late stage embryonic mice and analysed for carnosine expression. The yield of carnosine neurones was twice as high when the OE cells were seeded along with the olfactory bulb cells. Carnosine neurones resulted from both in vitro survival and neurogenesis, and were associated with clusters of underlying flat cells immunopositive for keratin. Our results demonstrate that olfactory neurones expressing their neurotransmitter carnosine can be studied in culture, and the close association with keratin-immunopositive basal cells suggests that they are dependent on these cells for survival and/or differentiation.

Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology.

Intranasal irrigation of mice with 0.17 M ZnSO4 solution results in the immediate and total loss of the ability to find a buried food pellet. This anosmia persists for 6 weeks in at least 80% of the treated mice and for 4 months in half of the animals. This marked behavioral effect is matched by a long-term reduction of the levels of carnosine synthesis and transport in the primary olfactory pathway. These biochemical parameters are virtually undetectable at two weeks after treatment and even at one year after treatment do not exceed 5-10% of average control values. Light microscopic observations of tissues of the primary olfactory pathway at various times after treatment are consistent with these observations and indicate a substantial destruction of the olfactory epithelium with subsequent atrophy of the olfactory bulb. At very long intervals after treatment, some receptor regeneration is apparent with accompanying reinnervation of the olfactory bulb. Estimates from microscopy and biochemistry suggest that much less than 10% of the normal complement of functioning receptor cells is adequate to give apparently normal food-finding behavior.

Biosynthesis of carnosine in primary cultures of rat olfactory bulb.

Primary cultures of glia cells obtained from adult rat olfactory bulb synthesize carnosine (beta-alanyl histidine). The rate of synthesis increases the older the culture is and is enhanced by the addition of dibutyrylcyclic-AMP (dBcAMP) to the medium. Millimolar concentrations of this agent intensify galactocerebroside (GalC) staining compared to control cultures. Removal of GalC positive cells through antibody and complement cell killing decreases carnosine synthesis to a minimum. Cultures prepared from olfactory bulb of new-born rats contain neuron specific enolase (NSE) positive neurons and GalC positive ensheathing cells. Such cultures produce carnosine. When switched to nerve growth factor (NGF) depleted medium containing dBcAMP the share of neurons in the culture decreases drastically with time and concomitantly an increase of the relative rate of carnosine synthesis is observed. After 1 week in such medium the cultures contain almost no NSE positive cells. Virtually all cells express glial fibrillary acidic protein (GFAP) and are GalC positive. These data suggest that carnosine is synthesized by the ensheathing cells of the olfactory bulb and not by olfactory neurons.

Effect of carnosine administration on metabolic parameters in bilharzia-infected hamsters.

Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in muscles, brain and other tissues. This study was designed to test the ability of carnosine to offset metabolic disturbances induced by Schistosoma mansoni parasitism. Results indicate that parasitic infection caused elevation of liver weight/body weight in S. mansoni-infected hamsters, induced lipid peroxidation and reduced glycogen levels. Moreover, adenylate energy charge (AEC) and ATP/ADP and ATP/AMP concentration ratios were markedly lower in infected hamsters. Administration of carnosine (10 mg/day) for 15 days concurrent with infection effectively reduced worm burden and egg count. Administration of carnosine 2 and 4 weeks post-exposure only partially ameliorated the S. mansoni effects on metabolism. Carnosine treatment also normalized most of the parameters measured, including glycogen repletion, the antioxidant status and AEC. These finding support the use of carnosine for possible intervention in schistosomiasis.

[Development of olfactory epithelial grafts in the anterior chamber of the eye]. / Razvitie transplantatov oboniatel'nogo épiteliia v peredenei kamere glaza.

Olfactory epithelium of newborn rats was transplanted into the anterior eye chamber of the adult rat. Within 6-8 weeks the transplants increased in weight by a factor of 20-50. Morphological analysis has shown the cells similar to olfactory sensory neurones in the grafts. Electroolfactograms obtained with n-amyl acetate and camphor had the amplitude of about three times less and the duration of about 8-10 times more than those from the normal olfactory epithelium at the same concentration of stimuli. Within six hours after 3H-beta-alanine had been introduced into the anterior eye chamber, 72% of the label were present in the carnosine fraction. The data obtained suggest that olfactory sensory neurones appear in the olfactory epithelium grafts into the anterior eye chamber.

[Activity of several the mediator systems of the brain during hyperbaric oxygenation]. / Aktivnost' nekotorykh mediatornykh sistem mozga pri giperbaricheskoi oksigenatsii.

Dynamics of noradrenalin, adrenalin, dipeptide homocarnosine, GABA, hystidine, MAO activity (with noradrenalin as substrate), and homocarnosincarnosinsynthetase in the rat brain under hyperbaroxygenation, was studied. Exposure of the rats to 4 atm of oxygen for 1 hr leads to the 70--80% decrease of noradrenalin content in all brain areas. Adrenalin level does not change. MAO activity increases in hypothalamus remaining at the control level in cortex, decreases significantly in medulla oblongata, and complete inhibition of the enzyme activity occurs in the midbrain. The hyperbaric conditions cause no considerable changes in homocarnosine, GABA, and hystidine levels in all the areas under study. A profound decrease of homocarnosine content and inhibition of homocarnosine--carnosinesynthetase follows the convulsive phase of oxygen intoxication especially in the midbrain (69.9% and 50.3%, resp.).