Statins inhibit the biosynthesis of ..
Lovastatin and other statins inhibit HMG-CoA reductase, which carries out an early step in the sterol biosynthesis pathway
Statin Drugs Revisited by Jeffrey Dach MD
Medicinal chemist of the University of Minnesota, Twin Cities, praises Hoffmeister and his coworkers for their painstaking efforts to elucidate the biosynthesis of psilocybin. “Our knowledge of the biosynthesis of fungal natural products has lagged behind our understanding of the corresponding bacterial biosynthetic pathways owing to a number of unique challenges,” Aldrich says. For instance, the genomes of fungi are more complex than bacteria, many fungi are still not amenable to genetic manipulation, and cultivating fungi to produce sufficient amounts of desired metabolites is not always straightforward. “The new work lays the foundation for developing a fermentation process for production of this powerful psychedelic fungal drug, which has a fascinating history and pharmacology,” Aldrich adds.
Janis Fricke, Felix Blei, and of Friedrich Schiller University Jena have identified and characterized to the greatest extent so far the four enzymes that the mushrooms use to make psilocybin. The team then developed the first enzymatic synthesis of the compound, setting the stage for its possible commercial production ( 2017, DOI: ).
This article takes a critical look at statin anti-cholesterol drugs
This all changed with the advent of statins, which first reached the market in 1987. Li justifiably gives a great deal of credit to the father of this field, biochemist Akira Endo, who isolated the first statin, mevastatin, from fermentation broths while at Sankyo, a Japanese pharmaceutical company. Endo was searching for inhibitors of the enzyme HMG-CoA reductase, a key to the biosynthesis of cholesterol, as it was envisioned that blocking the synthesis of cholesterol would result in lower cholesterol levels in plasma. In yet another example of a compound being used to elucidate biological processes, Michael S. Brown and Joseph L. Goldstein, doctors in the department of medicine at the University of Texas Southwestern Medical Center, demonstrated that blocking HMG-CoA reductase results in an upregulation of LDL receptors on the liver, thereby draining plasma of LDL. Brown and Goldstein won the Nobel Prize in 1985 for this work. Ironically, Sankyo never developed statins commercially.
“The publication by Hoffmeister and colleagues highlights a terrific example of genomics-based biocatalyst-pathway discovery,” adds natural products researcher of the University of Kentucky. “While psilocybin biosynthesis derives from a series of fairly simple chemical transformations, this new study identifies the contributing genes and biocatalysts for the first time and, importantly, provides strong evidence to support a revision of the order of the key steps proposed more than five decades ago. This work clearly sets the stage for bioengineered psilocybin production and/or for analogs that may serve as compelling alternatives to existing synthetic strategies.”
The Synthesis of Cholesterol. - Cholesterol-And …
of the synthesisof oleic acid ().
Klenk E identified sphingomyelin as the stored phospholipid in cells frompatients with Niemann-Pick disease ().
Von Euler US identified a lipid-soluble substance from semen which stimulatesuterine smooth muscle contraction and named it prostaglandin ()
In addition to the well-known effect of statins on low-density lipoprotein cholesterol (LDL-C) via inhibition of HMG-CoA reductase, a meta-analysis of 6 RCTs demonstrated that statin treatment is also associated with significant reductions in plasma CoQ10 concentrations. This may be due to statin-induced inhibition of farnesyl pyrophosphate production. To visualise the cholesterol biosynthesis pathway, see .
Rosuvastatin to Prevent Vascular Events in Men and …
Bile Acid Synthesis, Metabolism and Biological Functions
Lovastatin - Wikipedia
Bile Acid Synthesis and Utilization
Statin Drugs Revisited
The end products of cholesterol utilization are the bile acids
by Jeffrey Dach MD
We have got cholesterol completely wrong – Zoë …
Now that the results of long term studies of statin use have been published, few would argue the effectiveness of statin drugs in reducing cardiovascular disease risk. To be sure, other substances having nothing or little to do with our alleged nemesis, cholesterol, also have demonstrated considerable benefit in this regard. Such therapies include omega 3, , , anti-oxidants and even buffered . But in considering only the statins, study after study has shown the benefit of these agents in reducing the risk of heart attack and stroke, whether used for primary or secondary prevention. However, almost buried in this barrage of positive results is our growing research evidence that this reduction of cardiovascular disease morbidity and mortality from statin use has occurred independently of cholesterol effect. Regardless of the cholesterol level of the subject at the start of statin therapy, whether normal or high and regardless of the level of cholesterol reduction, whether great or small or none at all, statins, originally felt to work solely as an inhibitor of cholesterol biosynthesis, appear to work independently of cholesterol. Just what is going on here? Weren't we all taught years ago that only by decreasing serum cholesterol by haranguing our patients these past 35 years as to the merits of a low fat/low cholesterol diet and by writing expensive prescriptions for a long list of increasingly potent cholesterol "busting" drugs could we expect to reduce cardiovascular disease risk? And now we find statin benefit independently of any cholesterol factor. Isn't cholesterol still "public health enemy number one"? Can't we still use the "C" word to frighten small children?
# Question of the day | Biochemistry for Medics – …
While the story of statins is the focus of the book, Li also provides a veritable history of pharmaceutical science particularly around cholesterol. It is amazing to read about the number of Nobel Prizes that have been awarded for work in the cholesterol field, ranging from the identification of the molecular structure of cholesterol to the total synthesis of cholesterol, its biosynthesis, and the regulation of LDL (low-density lipoprotein) cholesterol through the liver. In covering almost a century of research on this topic, Li brings to life the great work in the 1940s and '50s of some of the early giants of synthetic organic chemistry such as Robert Robinson and Robert Burns Woodward. It is also striking how much has changed in science over the past several decades. For example, the elegance of natural products synthesis, so crucial in elucidating biological mechanisms, is now taken for granted.
Lipitor 10 mg film-coated tablets - - (eMC) - Medicines
discovered the first inhibitor of cholesterol biosynthesis through the inhibition of HMG-CoA reductase, mevastatin (the first ) extracted from ().
Hopanols have been described in living bacteria ().
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