Systems IntegrationPsychoneuroimmunology
Len Wisneski in The Scientific Basis of Integrative Health, 2017
Our second example of a paracrine messenger that affects the pituitary in a totally novel manner is α-MSH. The classic hormone α-MSH is synthesized and secreted by anterior pituitary cells. The actions of the novel immune-cell-secreted, pituitary-derived α-MSH are different and distinct from the well-known classic endocrine effects. The pituitary-derived α-MSH hormone stimulates secretion of prolactin (which is also synthesized in the anterior pituitary) by paracrine action. The secretion of the prolactin is significant enough to then elevate thyrotropin-releasing hormone (TRH) and adenosine triphosphate (ATP) (Schwartz, 2000). TRH stimulates the release of thyrotropin (which helps stimulate and sustain hormonal secretions from the thyroid) from the anterior pituitary. ATP synthase is an enzyme that is capable of producing high amounts of chemical energy for the body and, thus, is crucial as the source of energy for many physiological functions, from muscle contraction to metabolism. Just to add one more layer of interaction, recall that we just learned that immune-cell-secreted, pituitary-derived galanin decreases prolactin and, here, that α-MSH increases it. The intricacy of interaction is staggering.
New Developments in Drug Treatment
Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies in Clinical Tuberculosis, 2020
ATP synthase is an attractive drug target because it is essential, and ATP is required even in persistent bacterial states.13 Therefore it was not surprising to find that bedaquiline is active on dividing and non-dividing bacteria14 and displays time-dependent bactericidal activity both in vitro and in vivo. It has been extensively studied in the murine model and has emerged as a potential key component of new drug regimens.15 It is highly active given as mono-therapy and can substitute for any of the three first-line drugs,10,16 exhibits strong synergy with PZA17 and can shorten MDR-TB treatment.18 With the aim of developing a universal regimen, active against drug-susceptible and -resistant organisms various combinations of pretomanid (PA-824), clofazimine, sutezolid, bedaquiline, rifapentine and pyrazinamide were evaluated in a long-term mouse model. In terms of relapse-free cure after SCC, only regimens with bedaquiline were successful indicating its importance to new regimens.15
Framework
Peter W. Hochachka in Muscles as Molecular and Metabolic Machines, 2019
A similar PCr conduit from ATP synthesis sites to ATP utilization sites occurs during aerobic metabolism. Here, a mitochondrial isozyme of CPK unique to skeletal muscle (sarcomeric mCPK) is thought to facilitate formation of contact zones between the outer and inner mitochondrial membranes so as to interact with mitochondrial oxidative phosphorylation. ATP formed at the ATP synthase in the matrix is preferentially directed toward the adenylate translocase and thence to mCPK. PCr formed in this reaction is considered the effective end product of oxidative phosphorylation. It exits through an anion-preferring, high conductance channel (porin) in the outer membrane of the mitochondria and becomes the substrate for ATPase-linked CPK isoforms.
Passive heat stress induces mitochondrial adaptations in skeletal muscle
Published in International Journal of Hyperthermia, 2023
Erik D. Marchant, W. Bradley Nelson, Robert D. Hyldahl, Jayson R. Gifford, Chad R. Hancock
Oxidative phosphorylation is the process by which the majority of ATP is produced in muscle cells. This process involves a series of redox reactions which result in electrons being transferred through protein complexes (referred to as complexes I-IV), ultimately reacting with molecular oxygen. These redox reactions are coupled with the transfer of protons (H+ ions) out of the matrix, resulting in an increase in membrane potential. Protons then flow down a gradient and drive the production of ATP, catalyzed by ATP synthase. In response to changes in energy demand, like muscle disuse or endurance exercise training, skeletal muscle is able to increase or decrease its capacity to perform oxidative phosphorylation via changes in the density of mitochondrial enzymes in existing mitochondria and/or alteration of mitochondrial volume [3,7].
Methods in marine natural product drug discovery: what’s new?
Published in Expert Opinion on Drug Discovery, 2023
Jehad Almaliti, William H. Gerwick
Synthetic biology approaches have been recently applied to structure modifications and analog generation. Noteworthy examples include reprogramming of polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) modular enzymes, although these approaches usually suffer from low yields. Alternatively, characterization of enzymes involved in NP biosynthetic transformations is allowing their use as synthetic reagents of exceptional utility. For example, the γ-lactam-β-lactone bicyclic core of the proteasome inhibitor salinosporamide A is formed by a single standalone ketosynthase (KS), SalC, and represents a major step toward harnessing the activity of this enzyme for the efficient production of new-to-nature bioactive salinosporamides [14]. The Abe group has demonstrated a useful strategy for engineering NRPS-PKS module enzymes, based on nature’s diversification of the domain and module organization. As a result, they have accomplished ring contractions, ring expansions, and alkyl chain diversification of a family of cyclic depsipeptides (5) [15].
Effects of L-arginine supplementation on biomarkers of glycemic control: a systematic review and meta‐analysis of randomised clinical trials
Published in Archives of Physiology and Biochemistry, 2023
Elham Karimi, Elaheh Hatami, Abed Ghavami, Amir Hadi, Mina Darand, Gholamreza Askari
The results indicated that L-arginine can change the molecular and cellular levels through complex mechanisms (Faldetta et al. 2002). It has been proved that effects of L-arginine on metabolic responses are due to the formation of NO. The availability of NO can multiply glucose metabolism through the NO/c-GMP cascade (Palmer et al. 1988, Balon and Nadler 1994, Monti et al. 2000). Likewise, some investigations implied that L-arginine improved the glucose transporter type 4 (GLUT4) protein substance in skeletal muscle cells that may increase glucose transport. In contrast, it multiplies glycogen synthase kinase 3 (GSK–3) phosphorylation and glycogen synthase. These implicit effects of L arginine may be caused by variations in muscle cell differentiation (de Castro Barbosa et al. 2013). Part of the positive effects of l-arginine on insulin sensitivity can be attributed to an increase of endothelial dysfunction (Wascher et al. 1997, Böger 2008, Monti et al. 2012). Insulin resistance is due to NO disability to produce its messenger, causing a decrease both in cGMP production and in insulin’s ability to generate vasodilatation. The assumption was in accordance with Petrie at al ’s (Petrie et al. 1996) finding, suggesting that insulin resistance and endothelial response to inhibition of NO synthesis are correlated, also they verified that the vasodilatory response is lessened in insulin-resistant individuals.
Related Knowledge Centers
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