Structural Aspects of Luteinizing Hormone Actions
Mario Ascoli in Luteinizing Hormone Action and Receptors, 2019
The reagents employed in the amino functional group studies as summarized above undoubtedly owe a portion of their effect to simple steric effects, i.e., they simply get in the way for normal hormone-receptor interactions. Unfortunately, there is no ready measure for the extent to which this is true in contrast to the elimination of the function of the lysine residues in question. Perhaps the simplest substituent group possible is proton replacement (with deuterium or tritium). Although these replacements are useful for labeling, they are not useful for measuring significant changes in biological activity from their effects on the amino group, which should be slight if detectable at all. For a substituent group with the next order of simplicity the methyl group is the functional group of choice. This group has the added advantage that it may be inserted by reductive methylation with tritiated borohydride to provide a built in analytical tracer. Two groups have used this approach: Ascoli and Puett61 and de la Llosa and colleagues.55 That the methyl group provides very little interference with hormone function is apparent since the resulting preparations have the same (or sometimes higher) potency as the starting preparation. On the other hand, when the subunits were isolated, then methylated, the recombination was less efficient and the resulting hybrids (only one subunit methylated) were less potent than the native subunit recombinants.55
Metabolism of Phosphonates
Richard L. Hilderbrand in The Role of Phosphonates in Living Systems, 2018
The only phosphonate-containing antibiotic whose biosynthesis has been investigated is fosfomycin (formerly phosphonomycin) which was originally isolated from used culture medium of Streptomyces fradiae.4 Fosfomycin, (—)1R,2S-cis- 1,2-Epoxypropylphosphonic acid, is a secondary metabolite of the organism and is produced in significant quantities only when the growth of the organism is slowing from logarithmic to stationary phase.70 The compound is clearly made as some two-carbon unit to which the methyl group is subsequently added.70 [14C-Methyl]-methionine and [U-14C]glycine provide the methyl group of fosfomycin.70,71 Methionine is also required as an inducer of fosfomycin synthesis since it has to be present in the original medium for optimum synthesis and cannot be replaced by other methyl group sources such as choline, betaine, or serine. Carbon sources which give increased yields of fosfomycin are, in order of the activity, malate, a–ketoglutarate and glutamate, oxaloacetate, and succinate. These are all intermediates or sources for intermediates in the citric acid cycle and gluconeogenesis.70
Genetics and exercise: an introduction
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
How does the CH3 methyl group become added to some cytosines and what is the consequence? Cytosines are methylated by enzymes, called DNA methyltransferases. The resultant cytosine methylation then typically reduces gene transcription. This is because methylation reduces transcription factor binding to that region of DNA. Because CpG sites and CpG islands are located more frequently around promoter regions, reduced transcription factor binding after increased methylation suppresses gene transcription. In contrast, reduced methylation (demethylation or hypomethylation) of CpG sites in a promoter region can increase gene transcription, by allowing transcription factor binding. Exceptions are if increased methylation occurs in a silencer or repressor element where it can therefore increase transcription. CpG islands can be methylated (or demethylated) in the basal, natural state, but cytosine residues also become more or less methylated in response to nutrients, environmental stressors, exercise and other stimuli.
Nutrition Provides the Essential Foundation for Optimizing Mental Health
Published in Evidence-Based Practice in Child and Adolescent Mental Health, 2021
Julia J. Rucklidge, Jeanette M. Johnstone, Bonnie J. Kaplan
Methylation is one of many essential biochemical processes involved in gene regulation, whereby a methyl group (one carbon and three hydrogen atoms) is transferred to a molecule such as DNA. These newly methylated compounds are essential for a number of functions including: DNA synthesis and repair, neurotransmitter production (like serotonin), energy production, detoxification, gene regulation, hormone regulation, cell membrane repair, myelination, and immune function. The methylation-folate cycle, sometimes known as one carbon metabolism, requires specific nutrients (e.g., vitamins B2, B6, B12) acting as cofactors in order for the metabolic reactions to occur. Without an adequate supply, methylation will be impaired, which in turn may affect genetic expression and result in poor physical and mental health. Increasing the supply of nutrients has been shown to modestly increase methylation of the genome, illustrating the role that nutrients might play in gene modification (Stevens et al., 2018).
Epigenetic regulation by gut microbiota
Published in Gut Microbes, 2022
Vivienne Woo, Theresa Alenghat
DNA methylation is an epigenetic modification whereby methyl groups (-CH3) are covalently added to cytosine or adenine bases by DNA methyltransferases (DNMTs) using the donor metabolite SAM. Methylated DNA residues are often located within CpG Islands and are generally associated with gene repression by physically restricting access of regulatory mediators to the DNA, especially when located near gene promoters. Changes in DNA methylation were initial evidence that the microbiota influences the host epigenome. Specifically, DNA methylation of the 5ʹ CpG Island in the toll-like receptor 4 (Tlr4) gene was decreased in large intestinal IECs from GF mice compared to conventionally housed (CNV) mice, resulting in reduced Tlr4 expression and responsiveness to the pathogen-associated molecular pattern lipopolysaccharide (LPS).22 Demethylation was also detected at the chemokine ligand Cxcl16 gene in the colon and lungs of GF mice compared to CNV mice, which is consistent with decreased mucosal invariant natural killer T cell accumulation in absence of the microbiota.23 Microbiota also directed DNA methylation in regulatory T cells (Tregs) by increasing expression of Uhrf1, a DNA methylation adaptor protein that complexes with Dnmt1 and HDAC1.24 T-cell specific deletion of Uhrf1 impaired normal cell cycle gene expression in Tregs and consequently led to spontaneous colitis.
In vitro and in silico β-lactamase inhibitory properties and phytochemical profile of Ocimum basilicum cultivated in central delta of Egypt
Published in Pharmaceutical Biology, 2022
Nagwa A. Shoeib, Lamiaa A. Al-Madboly, Amany E. Ragab
The 1H NMR spectrum (provided in supplementary file) indicated the presence of five aromatic protons suggesting a monosubstituted benzene ring. The 13C NMR spectrum (provided in supplementary file) showed eight signals accounting for 10 carbons. The aromatic carbons were represented by chemical shifts at δC 134.3 (C1), 128.8 (C2,6), 130.2 (C3,5) and 128.1 (C4), while the olefinic carbons (C7 and C8) exhibited chemical shifts at δC 117.2 and 144.9. Signals for carbonyl group at 167.8 (C9) and for deshielded alkyl carbon at δC 50.8 (C10) indicated an ester group. A methyl group peak at δH 3.79 confirmed a methyl ester. These spectral data are in good concordance with those in the literature for methyl cinnamate. The stereochemistry was identified as E based on the coupling constant for the trans protons JH7–H8=16 Hz (Spekreijse et al. 2012; Sitrallah et al. 2016).
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