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Exploration of nitrate-to-glutamate assimilation in non-photosynthetic roots of higher plants by studies of 15N-tracing, enzymes involved, reductant supply, and nitrate signaling: A review and synthesis.
Yoneyama, T, Suzuki, A
Plant physiology and biochemistry : PPB. 2019;:245-254
Abstract
Roots of the higher plants can assimilate inorganic nitrogen by an enzymatic reduction of the most oxidized form (+6) nitrate to the reduced form (-2) glutamate. For such reactions, the substrates (originated from photosynthates) must be imported to supply energy through the reductant-generating systems within the root cells. Intensive studies over last 70 years (reviewed here) revealed the precise mechanisms of nitrate-to-glutamate transformation in roots with elaborate searches of 15N-tracing, enzymes involved, the reductant-supplying system, and nitrate signaling. In the 1970s, the tracing of 15N-labeled nitrate and ammonia in the roots demonstrated the sequential reduction and assimilation of nitrate to nitrite, ammonia, glutamine amide, and then glutamate. These reactions involve nitrate reductase (NADH-NR, EC 1.7.1.1) in the cytosol, nitrite reductase (ferredoxin [Fd]-NiR, EC 1.7.7.1), glutamine synthetase (GS2, EC 6.3.1.2), and glutamate synthase (Fd-GOGAT, EC 1.4.7.1) in the plastids. NADH for NR is generated by glycolysis in the cytosol, and NADPH for Fd-NIR and Fd-GOGAT are produced by the oxidative pentose phosphate pathway (OPPP). Electrons from NADPH are conveyed to reduce NIR and Fd-GOGAT through Fd-NADP+ reductase (FNR, EC 1.6.7.1) specifically in the roots. Physiological and molecular analyses showed the parallel inductions of NR, NIR, GS2, Fd-GOGAT, OPPP enzymes, FNR, and Fd in response to a short-term nitrate supply. Recent studies proposed a molecular mechanism of nitrate-induction of these genes and proteins. Roots can also assimilate the reduced form of inorganic ammonia by the combination of cytosolic GS1 and plastidic NADH-GOGAT.
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Conformational dynamics play important roles upon the function of N-acetylglutamate kinase.
Yang, X
Applied microbiology and biotechnology. 2017;(9):3485-3492
Abstract
N-acetylglutamate kinase (NAGK) catalyzes the phosphorylation of N-acetylglutamate. In many bacteria, NAGK catalysis is the rate controlling step in the L-arginine biosynthesis pathway from glutamate to L-arginine and is allosterically inhibited by L-arginine. Many data show that conformational dynamics of NAGKs are essential for their function. The demonstration of the conformational mechanism provides a potential way to improve the yield of arginine. Due to the lack of NAGK catalysis step in arginine synthesis route of mammals, the elucidation of the dynamic mechanism can also provide a way to design a new antivirus drug. This paper reviews how the dynamics affect the activity of NAGKs and are controlled by the effectors. X-ray crystallography and modeling data have shown that in NAGKs, the structural elements required for inhibitor and substrate binding, catalysis and product release, are highly mobile. It is possible to eliminate the inhibition of the arginine and/or block the synthesis of arginine by disturbing the flexibility of the NAGKs. Amino acid kinase family is thought to share some common dynamic features; the flexible structural elements of NAGKs have been identified, but the details of the dynamics and the signal transfer pathways are yet to be elucidated.
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Glutamatergic NMDA Receptor as Therapeutic Target for Depression.
Réus, GZ, Abelaira, HM, Tuon, T, Titus, SE, Ignácio, ZM, Rodrigues, AL, Quevedo, J
Advances in protein chemistry and structural biology. 2016;:169-202
Abstract
Major depressive disorder (MDD) affects approximately 121 million individuals globally and poses a significant burden to the healthcare system. Around 50-60% of patients with MDD respond adequately to existing treatments that are primarily based on a monoaminergic system. However, the neurobiology of MDD has not been fully elucidated; therefore, it is possible that other biochemical alterations are involved. The glutamatergic system and its associated receptors have been implicated in the pathophysiology of MDD. In fact, the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor, is a binding or modulation site for both classical antidepressants and new fast-acting antidepressants. Thus, this review aims to present evidence describing the effect of antidepressants that modulate NMDA receptors and the mechanisms that contribute to the antidepressant response.
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In Search of a Safe Natural Sleep Aid.
Rao, TP, Ozeki, M, Juneja, LR
Journal of the American College of Nutrition. 2015;(5):436-47
Abstract
Sleep deprivation is associated with an elevated risk of various diseases and leads to a poor quality of life and negative socioeconomic consequences. Sleep inducers such as drugs and herbal medicines may often lead to dependence and other side effects. L-Theanine (γ-glutamylethylamide), an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of α brain waves without additive and other side effects associated with conventional sleep inducers. Anxiolysis is required for the initiation of high-quality sleep. In this study, we review the mechanism(s), safety, and efficacy of L-theanine. Collectively, sleep studies based on an actigraph, the obstructive sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO) and automatic nervous system (ANS) assessment, sympathetic and parasympathetic nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the administration of 200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis. Because L-theanine does not induce daytime drowsiness, it may be useful at any time of the day. The no observable adverse effect level (NOAEL) for the oral administration of L-theanine was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS Sleep deprivation-associated morbidity is an increasing public health concern posing a substantial socioeconomic burden. Chronic sleep disorders may seriously affect quality of life and may be etiological factors in a number of chronic diseases such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep inducers are sedatives and are often associated with addiction and other side effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis. This review suggests that L-theanine is a safe natural sleep aid.
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Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis.
Camfield, DA, Stough, C, Farrimond, J, Scholey, AB
Nutrition reviews. 2014;(8):507-22
Abstract
A systematic review and meta-analysis was conducted on 11 randomized placebo-controlled human studies of acute effects of tea constituents L-theanine and epigallocatechin gallate, administered alone or in combination with caffeine, on cognitive function and mood. The outcome measures of mood were alertness, calmness, and contentedness, derived from the Bond-Lader scales, and state anxiety, from the State-Trait Anxiety Inventory. Cognitive measures assessed were attentional switch, intersensory attention, and rapid visual information processing. Standardized mean differences between placebo and treatment groups are presented for each study and outcome measure. Meta-analysis using a random-effects model was conducted when data were available for three or more studies. Evidence of moderate effect sizes in favor of combined caffeine and L-theanine in the first 2 hours postdose were found for outcome measures Bond-Lader alertness, attentional switching accuracy, and, to a lesser extent, some unisensory and multisensory attentional outcomes. Moderator analysis of caffeine and L-theanine doses revealed trends toward greater change in effect size for caffeine dose than for L-theanine dose, particularly during the first hour postdose.
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Acute effects of tea consumption on attention and mood.
Einöther, SJ, Martens, VE
The American journal of clinical nutrition. 2013;(6 Suppl):1700S-1708S
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Abstract
Tea has historically been associated with mood and performance benefits, such as relaxation and concentration. This review summarizes the research on the acute effects of tea, and its ingredients theanine and caffeine, on attention and mood. Consistent with abundant research on the benefits of caffeine, the performance benefits of tea were identified in a number of studies, with particularly consistent evidence for improved attention. Tea consumption also consistently improved self-reported alertness and arousal, whereas effects on pleasure or relaxation were less consistent. In addition to the research on caffeine in real-life performance, 2 recent studies have provided a broader perspective on tea's effects on psychological function in that they showed beneficial effects in related areas such as work performance and creativity. These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.
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Beyaz®: an oral contraceptive fortified with folate.
Fruzzetti, F
Women's health (London, England). 2012;(1):13-9
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Abstract
Beyaz(®) (Bayer HealthCare Pharmaceuticals, Berlin, Germany) consists of 28 film-coated tablets: 24 tablets each containing 3 mg drospirenone plus 20 µg ethinylestradiol (EE) and 451 µg levomefolate calcium followed by four tablets, each containing 451 µg levomefolate calcium. It has the same indications of the parent compound 20 µg EE/3 mg drospirenone in a 24/4-day regimen (i.e., contraception, moderate acne, premenstrual dysforic disorder). In addition, the 24-day regimen with 20 µg EE/3 mg drospirenone/levomefolate calcium assure significant increases in red blood cell and plasma folate levels reaching values indicated to be protective in reducing the risk of neural tube defects. A progressive decrease in folate levels has been observed in women taking a 30 µg EE pill fortified with the same dose of levomefolate calcium upon discontinuation. At 4 and 8 weeks following cessation of the oral contraceptive, red blood cell folate levels >906 nmol/l were measured in 85 and 60% of women respectively. Because of this, the folate-containing pill may aid in reducing the risk of neural tube defects in a pregnancy conceived during use or shortly after the discontinuation of the product.
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Comprehensive evaluation of Safyral(®) 2012.
Nelson, AL
Women's health (London, England). 2012;(6):619-33
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Abstract
The incidence of pregnancies affected with neural tube defects (NTDs) has been reduced by food fortification programs and public health campaigns promoting folic acid supplementation, but the incidence of NTDs in the USA has not achieved the full potential reduction expected with adequate periconceptional folate utilization. In seeking new ways to access sexually active women at risk for pregnancy, one option would be to link folic acid supplementation to contraceptive use. Since birth control pills are the most popular method of reversible contraception in the USA, it would seem quite logical to find a way to supplement them. To this end, a very efficient folate, levomefolate calcium salt (metafolin), has been added to drospirenone-containing oral contraceptives in equimolar concentrations to the recommended supplements of folic acid to reduce the risk for pregnancy and to reduce the risk of NTDs in pregnancies that occur while women are taking the pill or shortly after they discontinue its use. This article will focus on the need for such folate supplementation and will summarize the contraceptive and noncontraceptive benefits of the 30 µg EE/3 mg drospirenone pill (Yasmin(®), Bayer Healthcare, NJ, USA) to which has been added 451 metafolin (Safyral(®), Bayer Healthcare). The new information about thromboembolism risks associated with use of drospirenone-containing pills is also discussed.
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[Glutamatergic conception of mood disorders].
Permoda-Osip, A, Rybakowski, J
Psychiatria polska. 2011;(6):875-88
Abstract
The neurotransmitter theories of the pathogenesis and treatment of mood disorders presented so far focused mainly on serotonergic and catecholaminergic (noradrenergic and dopaminergic) transmission. In recent decades the attention has been also directed towards a role in the pathogenesis of mood disorders of stress axis dysregulation and of neuroplasticity disturbances, which involve the glutamatergic system. In this paper, a role of glutamatergic neurotransmission in the pathogenesis and treatment of unipolar and bipolar affective illness is presented. In the first part, a role of glutamatergic neurotransmission in the central nervous system is presented, with special focus on glutamatergic receptors. The results of molecular-genetic studies pointing to an association between glutamatergic system genes and a predisposition to unipolar and bipolar affective illness are discussed. In the next part, a summary of neurobiological, including neuroimaging findings as to changes in glutamatergic system in mood disorders is done. Following this, a role of glutamatergic system in the mechanism of action of antidepressant and mood-stabilizing drugs as well as therapeutic activity of drugs modifying glutamatergic system is reviewed. Glutamatergic conception of mood disorders allows for a new look on the pathogenesis and treatment of unipolar and bipolar affective illness.
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The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium.
Rapkin, RB, Creinin, MD
Expert opinion on pharmacotherapy. 2011;(15):2403-10
Abstract
INTRODUCTION Neural tube defects are the second most common congenital anomaly in the United States, although their incidence may be decreased by periconception folic acid supplementation. A new oral contraceptive containing drospirenone and ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk of neural tube defects in pregnancies conceived while taking or shortly after discontinuing this pill. AREAS COVERED Because of its novelty, very few studies have been performed to evaluate the efficacy, side effects and safety related to contraception, premenstrual dysphoric disorder and acne; therefore, literature evaluating similar contraceptives without levomefolate is reviewed. Additionally, we review studies evaluating the addition of levomefolate calcium to oral contraceptives containing 3 mg drospirenone and either 20 or 30 μg ethinyl estradiol. To date, no study has been performed to evaluate the effect this new oral contraceptive has on reducing the incidence of neural tube defects. EXPERT OPINION This new pill has similar contraceptive efficacy, side effect, safety and benefits profile to other drospirenone-containing contraceptives. While also approved to prevent neural tube defects, no studies validate this claim and physician time is better spent counseling women, regardless of contraceptive choice, on the importance of folic acid supplementation during the child-bearing years.