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Impairment of Lipid Metabolism in Ischemic and Reperfused Myocardial Tissue
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
Ger J. van der Vusse, Marc van Bilsen, Robert S. Reneman
Lack of oxygen has profound effects on myocardial lipid homeostasis. During the initial phase of ischemia, lipid intermediates such as hydroxy fatty acids, acylCoA, and acylcamitine accumulate in the oxygen-deprived tissue. The turnover rate of endogenous triacylglycerol is greatly enhanced due to the mass action of glycerol 3-phosphate produced in the glycolytic pathway. As a consequence, a substantial percentage of the anaerobically produced ATP is consumed in this “futile” cycle. When the ischemic period prolongs, nonesterified fatty acids (NEFA) start to accumulate in the tissue affected. The presence of nonesterified arachidonic acid in this lipid fraction strongly suggests degradation of endogenous phosphoglycerides, important constituents of myocardial membranes. Reinstallation of flow through the previously ischemic tissue results in an enhanced accumulation of NEFA, including arachidonic acid. This most likely indicates that reperfusion in itself may aggravate the injury inflicted upon the tissue during the preceding ischemic phase.
LIVER METABOLISM
Published in David M. Gibson, Robert A. Harris, Metabolic Regulation in Mammals, 2001
David M. Gibson, Robert A. Harris
The mctabolic flux through fattv acid synthesis is enhanced in response to the elevated insulin and glucose levels attending feeding. The rate of fatty acid oxidation is diminished in this state thus obviating a major futile cycle (Chapters 4 and 7). A direct coupling exists between the principal limiting enzymes of the two pathways: acetyl-CoA carboxylase (ACC in fatty acid synthesis) and carnitine palmitovl transferase I (CPT I in fatty acid oxidation). ACC becomes dephosphorylated and activated in response to insulin and the activities of protein phosphatases arc enhanced relative to diminishing protein kinase activities ofthe AMP kinase bicyclic system (Chapters J and 7). Both CPT 1 and a portion of liver ACC arc adherent to the outer aspect ofthe mitochondrial outer membrane (Chapter 6). Dephosphorylated ACC generates malonyl-CoA which is both the principal intermediate in fatty acid synthesis and a potent allosteric inhibitor of CPT I. Recent studies have demonstrated that certain cytoskclctal elements (intermediate filaments designated cytokeratins 8 and 18) also inhibit CPT I when polymerized in the dephosphorylated state (independent of malonyl-CoA). It is envisioned that a complex of ACC, CPT I and these cytokeratins may comprise a tightly integrateti control switch which turns down fatty acid oxidation while Je novo synthesis of fatty acids is underway. This pattern may be reversed by the addition of okadaic acid to hcpatocytes. Okadaic acid is a tumor promoter and a potent inhibitor of protein phosphatases 1 and 2A. It enhances fattv acid oxidation bv permitting phosphorylation and dissociation of the cytokeratins, as well as phosphorylation and inacti-vation of ACC, thus inhibiting malonvl-CoA production (ami fatty acid synthesis). In this regard it is interesting to note thai okadaic acid does not have an effect on hepatoma cells, suggesting that an impairment of this system attends oncogenic transformation.
Phenyl-substituted aminomethylene-bisphosphonates inhibit human P5C reductase and show antiproliferative activity against proline-hyperproducing tumour cells
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Giuseppe Forlani, Giuseppe Sabbioni, Daniele Ragno, Davide Petrollino, Monica Borgatti
On the whole, data strongly suggest that the antiproliferative activity of P5C reductase inhibitors is mediated by an interference with the proline-P5C cycle. In this half-biosynthetic, half-catabolic set of reactions, proline is oxidised by ProDH to P5C but the latter, instead of being further oxidised to glutamate in the mitochondrion by P5CDH, is reduced back to proline in the cytosol by P5C reductase (Figure 1). Without resulting in a net change of free proline level, this apparently futile cycle may allow the transfer of reducing equivalents from the cytosol to the mitochondrion, fuelling the respiratory chain11–13. An increased activity of this cycle can improve cancer cell survival, proliferation, and metastasis through a variety of mechanisms ranging from enhanced ATP production, nucleotide synthesis, anaplerosis, and redox homeostasis24. Inhibition of P5C reductase is therefore expected to interfere with all these mechanisms, hampering cell growth even without impacting on proline availability for protein synthesis.
Effect of xylitol tablets with and without red propolis on salivary parameters, dental biofilm and sensory acceptability of adolescents: a randomized crossover clinical trial
Published in Biofouling, 2020
Mariana Leonel Martins, Amanda Souza Nunes Monteiro, Thiago Isidro Vieira, Maria Bárbara de Carvalho Torres Guimarães, Letícia Coli Louvisse de Abreu, Lucio Mendes Cabral, Yuri Wanderley Cavalcanti, Lucianne Cople Maia, Andréa Fonseca-Gonçalves
Regarding the data obtained through the diet diaries, the adolescents maintained the same dietary pattern throughout the study. Patients with dental restorations showed a higher daily consumption of carbohydrates and a lower consumption of fruits, reinforcing the role of diet in the etiology of dental caries (Feldens et al. 2019). On the other hand, saliva acts in the prevention of caries lesions due to its properties of mechanical cleaning, transport of calcium, phosphate, and fluoride ions to re-mineralize enamel. Also, xylitol stimulated the saliva flow, it has specific antibacterial properties for generating a ‘futile cycle’ that effectively eliminates stored intracellular energy and decreases bacterial growth and acid production (Ly et al. 2006). Thus, products that stimulate the saliva flow can reduce dental biofilm formation (Kakuta et al. 2003). An improvement was only observed in the salivary parameters immediately after the consumption of the first tablet for both types, but there were no intragroup and intergroup variations after seven days. Furthermore, the weight of biofilms remained constant before and after using the tablets and no difference between the groups was verified. This can be justified due to the ability of the tablets to exhibit a substantial increase in the salivary flow rate for a short period of time (20 min) after tablet consumption (Da Mata et al. 2009). Also, the interventions were carried out over a short time period to detect possible changes in these parameters.