Introduction
The mountain range that Ancel Keys and Bryan Mattews ascended
Andes Mountains
The two forms of familial hypercholesterolemia (FH), an inherited disease
Heterozygous and homozygous
By age ten Akira Endo was fascinated by these two types of fungi
Mushrooms and molds
After ineffective results in rats and mice, Endo tested compactin on this group of organisms
Hens
The difference between compactin and lovastatin?
The addition of a methyl group
Keys and Matthews were studying the body's response to this on their expedition to the Andes
High altitudes
3-hydroxy-3-methylglutaryl coenzyme A reductase (“the reductase”) is the start of this pathway
Cholesterol synthesis
The fault of early heart disease drugs (inhibitors of cholesterol synthesis) was this
negative side effects
These two problems, discovered by toxicologists, halted the testing of compounds like compactin and lovastatin
Tumors in dog intestines and rat liver cell abnormalities
All the ingredients found in the K-ration
A piece of hard sausage or canned meat, dry biscuits, a block of chocolate, a stick of chewing gum, matches, and a couple of cigarettes
Keys found that people who consumed diets rich in fats had higher levels of this
Serum cholesterol
When cholesterol levels are low, the cells will draw cholesterol from this in the body
The bloodstream
The fungi Pythim ultimum and Penicillium citrinum stood out to Endo and his team by containing this property
Inhibition of reductase
Administration of compactin and lovastatin lowered blood cholesterol levels by increasing the number of these
LDL receptors
The cholesterol levels of East Finlanders were compared to the cholesterol levels of this country’s people.
Croatia
The large scale international study of heart disease, organized by keys
The Seven Countries Study
Normal cells contain this, while Familial hypercholesterolemia (FH) cells did not
Low density lipoprotein (LDL) receptors
This was a potent inhibitor of the reductase, effective at low concentrations
ML-236B (Compactin)
Brown, Goldstein, Keys, Merck’s perseverance and discoveries received substantial recognition while this scientist did not.
Akira Endo
Who applied for and received FDA approval for the lovastatin?
Merck
The 3,000 calories package created by Keys for paratroopers in the Army
K-ration
This type of feedback enables cells to maintain relatively stable levels of cholesterol
Negative Feedback
Monod and Endo both had applied this concept to substrates and their relationship to enzymes
“Lock and Key”
The relationship between compactin, LDL receptors, and FH patients shows that “rather than replacing genes, we can exploit regulatory principles” for this to happen
Make good genes work harder
How does this chapter relate to Ecology?
Group's response/ discussion