Introduction: Mechanisms of Enzyme Regulation

2015 ◽  
pp. 1-5
Keyword(s):  
Enzyme Regulation

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

2020 ◽  
Vol 20 ◽  
Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Quantum Chemical ◽  
Density Functional ◽  
Enzyme Regulation ◽  
Amide Derivatives ◽  
Pass Through ◽  
Hydrolysis Of ◽  
Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

Control of cAMP in lung endothelial cell phenotypes. Implications for control of barrier function

1999 ◽  
Vol 277 (1) ◽  
pp. L119-L126 ◽  
Author(s):  
Troy Stevens ◽  
Judy Creighton ◽  
W. Joseph Thompson
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Barrier Function ◽  
Enzyme Regulation ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Calcium Entry ◽  
Camp Accumulation ◽  
Camp Phosphodiesterase ◽  
Conversion Rates

Pulmonary microvascular endothelial cells (PMVECs) form a more restrictive barrier to macromolecular flux than pulmonary arterial endothelial cells (PAECs); however, the mechanisms responsible for this intrinsic feature of PMVECs are unknown. Because cAMP improves endothelial barrier function, we hypothesized that differences in enzyme regulation of cAMP synthesis and/or degradation uniquely establish an elevated content in PMVECs. PMVECs possessed 20% higher basal cAMP concentrations than did PAECs; however, increased content was accompanied by 93% lower ATP-to-cAMP conversion rates. In PMVECs, responsiveness to β-adrenergic agonist (isoproterenol) or direct adenylyl cyclase (forskolin) activation was attenuated and responsiveness to phosphodiesterase inhibition (rolipram) was increased compared with those in PAECs. Although both types of endothelial cells express calcium-inhibited adenylyl cyclase, constitutive PMVEC cAMP accumulation was not inhibited by physiological rises in cytosolic calcium, whereas PAEC cAMP accumulation was inhibited 30% by calcium. Increasing either PMVEC calcium entry by maximal activation of store-operated calcium entry or ATP-to-cAMP conversion with rolipram unmasked calcium inhibition of adenylyl cyclase. These data indicate that suppressed calcium entry and low ATP-to-cAMP conversion intrinsically influence calcium sensitivity. Adenylyl cyclase-to-cAMP phosphodiesterase ratios regulate cAMP at elevated levels compared with PAECs, which likely contribute to enhanced microvascular barrier function.

Abstract 3560: Use of Hyperpolarized Magnetic Resonance for Non-Invasive Observation of Metabolic Regulation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marie A Schroeder ◽  
Lisa C Heather ◽  
Helen J Atherton ◽  
Kieran Clarke ◽  
George K Radda ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Metabolic Regulation ◽  
Krebs Cycle ◽  
Enzyme Regulation ◽  
Product Inhibition ◽  
Acetyl Coa ◽  
Fed State ◽  
Fasted Rats ◽  
Pyruvate Ratio

Hyperpolarized magnetic resonance (HP MR) has enabled real time visualization of in vivo metabolism. In this study, we postulated that HP MR could also non-invasively provide a measure of metabolic regulation. We focused on regulation of pyruvate dehydrogenase (PDH), a highly controlled enzyme that catalyzes the oxidation of pyruvate to acetyl CoA and CO2/HCO3-. We compared PDH flux in conditions of normal and attenuated enzyme activity, and in the presence of normal and augmented Krebs cycle flux, to determine the contributions of PDH activity and end product inhibition to enzyme regulation. Six rats were examined in the fed and fasted states (to modulate PDH activity), with 40 μmol HP 13C1-pyruvate alone and 40 μmol HP pyruvate co-infused with 40 μmol malate (to manipulate Krebs cycle flux/acetyl CoA uptake). HP tracer was infused into the rats in an MR scanner and cardiac spectra were acquired every second for 1 min. Conversion of pyruvate to 13HCO3-was monitored and the 13HCO3-/pyruvate ratio was used as a marker of PDH flux. Infusion of malate increased PDH flux by 31% compared with pyruvate alone, indicating that removal of acetyl CoA by incorporation into the Krebs cycle increased PDH flux. PDH flux was 57% lower in fasted rats injected with pyruvate alone compared with fed rats, and did not change with malate co-infusion. Here, low PDH activity prevented additional enzyme flux. These results suggest that end product inhibition limits fed state PDH flux, whereas PDH activity regulates pyruvate oxidation in the fasted state. In conclusion, this study has provided evidence that HP MR may be useful to obtain details of metabolic regulation, rather than just reflecting metabolic state. Figure 1 Bicarbonate/pyruvate ratio in fed and fasted rats, following an injection of pyruate or pyruate plus malate. In fed rats, co-infusion of malate increased PDH flux by 31% compared with injection of pyruvate alone (*p=0.02). Fasting reduced PDH flux by 57% (**p=0.002) following injection of pyruvate alone. Co-infusion with malate did not affect PDH flux in fasted rats.

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