While narrowing the focus of action to the BCM, an unresolved question from that study was: What is the source of cholesterol that accumulates in the BCM?
Or, in other words, is the elevated cholesterol derived from the existing cellular pool or from an increase in the ., 2000) in which the authors employed an experimental design utilizing two radiolabeled compounds that would discriminate between the existing cellular pool of cholesterol and cholesterol synthesized H-labeled cholesterol levels in all hepatic subcellular fractions, but most dramatically in the BCM.
The two enzymes have opposing actions—any condition or intervention that results in the activation of HMG-Co A reductase with concurrent inhibition of cholesterol-7α-hydroxylase will result in cholesterol accumulation and cholestasis (Fig. These two key factors of methodology and experimental design were paramount to the success of the study, and as a result, the data sets obtained allowed the authors to further define the mechanism of Mn-BR-induced cholestasis.
Because of their observation that the activity of this enzyme was decreased by over 50% after the Mn-BR treatment regimen (Duguay ., 2000), the authors concluded that factors other than an enhanced rate of cholesterol synthesis must account for the accumulation of newly synthesized cholesterol.
Thus, prior to the present highlighted study, confounding data sets existed that could not explain the accumulation of newly synthesized cholesterol.
The clinical use or abuse of drugs, including gold salts, nitrofurantoin, anabolic steroids, estrogens and oral contraceptives, chlorpromazine, prochlorperazine, sulindac, cholesterol-lowering “statins,” cimetidine, erythromycin, tobutamide, imipramine, and some penicillin-based antibiotics and herbal remedies, can cause cholestasis (Chitturi and Farrell, 2001).
Exposure to these agents may reduce or block bile flow and precipitate liver injury, in part due to the toxicity of bile acids and other bile constituents.
In this article, the authors have extended their earlier work defining mechanisms associated with the manganese-bilirubin (Mn-BR) model of experimentally-induced intrahepatic cholestasis.
The authors have been using this model for over 20 years because of the similarities in the pathophysiological changes in BCM to those observed in cases of cholestasis in humans.
Our results demonstrate that quantum computers will be able to tackle important problems in chemistry without requiring exorbitant resources.
The article highlighted in this issue is “Synergistic Role of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Cholesterol 7α-Hydroxylase in the Pathogenesis of Manganese-Bilirubin–Induced Cholestasis in Rats,” by Marie-Yvonne Akoume, Shahid Perwaiz, Ibrahim M. Cholestasis is a general condition of multiple etiologies, hereditary and acquired, in which bile excretion from the liver is attenuated or blocked.
Here, we show how quantum computers can be used to elucidate the reaction mechanism for biological nitrogen fixation in nitrogenase, by augmenting classical calculation of reaction mechanisms with reliable estimates for relative and activation energies that are beyond the reach of traditional methods.
We also show that, taking into account overheads of quantum error correction and gate synthesis, a modular architecture for parallel quantum computers can perform such calculations with components of reasonable complexity.
The question left unanswered was this: What is the metabolic basis that accounts for the newly synthesized cholesterol in BCM in the Mn-BR cholestasis model?