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Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

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The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

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Wiley has a good interactive feature on their website that covers the structure and physiology of cholesterol, including the health implications.
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Figure 5: Wiley has a good interactive feature on their website that covers the structure and physiology of cholesterol, including the health implications.

Mentions: Statins act to lower the level of serum cholesterol. Cholesterols are lipids, and many students find lipid chemistry difficult, or at least hard to remember, perhaps because hydrophobic molecules get short shrift in the science curricula on a watery planet. Of course their hydrophobicity is what makes them so important and interesting. Without lipids there would be no cellular and subcellular compartments, no way to sequester all that watery chemistry, not to mention the interesting signaling functions of lipids. I think cholesterol is a good entry point into lipid chemistry because students can be motivated by the health connections. Wiley has a good interactive tutorial on cholesterol that you can find at www.wiley.com/college/boyer/0470003790/animations/cholesterol/cholesterol.swf (Figure 5). The graphics are highly schematic, but it's a good overview of cholesterol with some emphasis on aspects that relate to heart disease and statin action. The occasional pop-up quizzes help keep students’ attention and discourage just clicking through. It's good that this feature puts cholesterol in the context of the steroid family of molecules, but it's unfortunate that they don't put them in the broader context of fat and lipid molecules. William Reusch in the Department of Chemistry at Michigan State University has put together a nice online primer on organic chemicals, including lipids (www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/biomol.htm). It's not interactive or graphics driven, but it has excellent information, clearly and concisely presented. Satoshi Amagai has developed a pair of very nice features for the BioInteractive website on the molecular structure of fats (www.hhmi.org/biointeractive/obesity/obesity_molecular/01.html) and how the body uses fat (www.hhmi.org/biointeractive/obesity/obesity_processing_fat/01.html). The “How the Body Uses Fat” feature in particular helps clarify that the much discussed “good” (HDL) and “bad” (LDL) cholesterols are not cholesterol; they are large lipoprotein particles that transport cholesterol through the blood. Our understanding of the chemistry of cholesterol, its metabolism, and its physiological regulation is a triumph of basic research. But importantly, the earliest concerns about the potential health hazards of cholesterol came from physicians. To understand the relationship between clinical and basic research, it's necessary to consider some history.Figure 5.


Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

Wiley has a good interactive feature on their website that covers the structure and physiology of cholesterol, including the health implications.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105917&req=5

Figure 5: Wiley has a good interactive feature on their website that covers the structure and physiology of cholesterol, including the health implications.
Mentions: Statins act to lower the level of serum cholesterol. Cholesterols are lipids, and many students find lipid chemistry difficult, or at least hard to remember, perhaps because hydrophobic molecules get short shrift in the science curricula on a watery planet. Of course their hydrophobicity is what makes them so important and interesting. Without lipids there would be no cellular and subcellular compartments, no way to sequester all that watery chemistry, not to mention the interesting signaling functions of lipids. I think cholesterol is a good entry point into lipid chemistry because students can be motivated by the health connections. Wiley has a good interactive tutorial on cholesterol that you can find at www.wiley.com/college/boyer/0470003790/animations/cholesterol/cholesterol.swf (Figure 5). The graphics are highly schematic, but it's a good overview of cholesterol with some emphasis on aspects that relate to heart disease and statin action. The occasional pop-up quizzes help keep students’ attention and discourage just clicking through. It's good that this feature puts cholesterol in the context of the steroid family of molecules, but it's unfortunate that they don't put them in the broader context of fat and lipid molecules. William Reusch in the Department of Chemistry at Michigan State University has put together a nice online primer on organic chemicals, including lipids (www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/biomol.htm). It's not interactive or graphics driven, but it has excellent information, clearly and concisely presented. Satoshi Amagai has developed a pair of very nice features for the BioInteractive website on the molecular structure of fats (www.hhmi.org/biointeractive/obesity/obesity_molecular/01.html) and how the body uses fat (www.hhmi.org/biointeractive/obesity/obesity_processing_fat/01.html). The “How the Body Uses Fat” feature in particular helps clarify that the much discussed “good” (HDL) and “bad” (LDL) cholesterols are not cholesterol; they are large lipoprotein particles that transport cholesterol through the blood. Our understanding of the chemistry of cholesterol, its metabolism, and its physiological regulation is a triumph of basic research. But importantly, the earliest concerns about the potential health hazards of cholesterol came from physicians. To understand the relationship between clinical and basic research, it's necessary to consider some history.Figure 5.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

Show MeSH