50 
A Breakdown in the 
LDL System Can Mow 
Be Treated 
The low-density lipopro- 
tein (LDL) system works 
like a thermostat to 
ensure that the cell 
always has enough cho- 
lesterol for life and 
growth, without accumu- 
lating too much of it. 
Because of a defective 
gene, however, the cells 
of people with familial 
hypercholesterolemia 
(FH) are severely deficient 
in LDL receptors. Their 
livers manufacture 
cholesterol and release it 
into the blood, but since 
their cells do not have 
enough LDL receptors, 
not enough cholesterol is 
taken up. Instead, it begins 
to clog their arteries. 
People who have two 
genes for FH suffer from 
heart disease from a very 
early age, sometimes as 
early as age 1. Persons 
with only one defective 
gene do make some LDL 
receptors, but still have a 
high risk of heart attacks, 
and often have an attack 
before age 30. FH is a 
relatively common 
genetic disorder; as many 
as 1 person in 500 carries 
one copy of the defective 
gene. 
Michael Brown anti 
Joseph Goldstein of the 
University of Texas 
Health Science Center at 
Dallas determined both 
the precise genetic 
defects and the role of 
the LDL receptor in FH. 
In 1985, both men were 
awarded Nobel Prizes 
for this work. Their 
studies also led to the 
development of lovastatin, 
a drug to treat FH. 
Lovastatin has a dual 
action: It reduces the 
liver’s ability to manu- 
facture cholesterol so 
that fewer LDL’s enter 
the bloodstream, and it 
causes the LDL receptors 
that the person has to 
take up cholesterol more 
efficiently. 
The mechanism Brown 
and Goldstein outlined for 
LDL receptors is but one 
example of the process of 
receptor-mediated mem- 
brane transport. The 
cell also uses protein 
receptors to bind or take 
in such substances as 
insulin, transferrin (an 
iron-bearing compound), 
and cell complexes that 
are produced when the 
immune system is 
activated. 
