Goldstein, Joseph Leonard (1940– )

US geneticist who was awarded a Nobel Prize for Physiology or Medicine in 1985 with Michael Brown for their work on the regulation of cholesterol metabolism. They discovered that the gene mutated in familial hypercholesterolaemia, a condition in which patients have very high blood cholesterol, is the gene for receptors involved in the removal of cholesterol from the bloodstream.

How cholesterol is removed from the blood Goldstein and Brown worked out the steps involved in the uptake of cholesterol, in the form of low-density lipoprotein (LDL), in the blood plasma by the cells of the body. The LDL particles bind to their receptors and are then internalized by endocytosis (adsorption). In this manner an endocytic vesicle is formed which subsequently fuses with a lysosome (a digestive organelle inside a cell). Lysosomes contain all the degradative enzymes required to free the amino acids and cholesterol from the LDL particles. The receptors are freed to return to the plasma membrane of the cell.

Heredity Children who inherit the mutated gene from both parents are homozygous for the mutation and generally die of heart disease in childhood. Children who inherit one normal gene and one mutated gene, heterozygotes, have half the number of receptors that would be expected in a healthy person and have a milder disease than homozygotes for the mutation.

Life Goldstein was born in Sumter, South Carolina, and graduated from the University of Texas in medicine in 1966. While working as a junior doctor at the Massachusetts General Hospital in Boston, he met and began working with Brown; a collaboration which was to lead to the joint award of the Nobel Prize.