Lysosomes in Health and Disease 
Lysosomes are known to contain over 40 
different enyzmes that can digest almost 
anything in the cell, including proteins, RNA, 
DNA, and carbohydrates. These enzymes 
work best in environments more acidic than that 
found in the cytoplasm, and lysosomes are 
specially equipped to provide this acidic envi- 
ronment. As corrosive as these enzymes are, 
they do not ordinarily damage the cell because 
the lysosomal membrane remains intact. 
When cells are programmed to die in some 
normal process of embryonic development, 
however — for example, in the metamorphosis 
of insects — the lysosomes' membranes become 
permeable and release their enzymes to digest 
the cells from within. In very old cells, too, the 
lysosomes may release their contents, which 
destroy the cell. A more limited form of "autodi- 
gestion" can also occur in cells that have been 
injured by lack of oxygen, an excess of vitamin 
A, exposure to certain cancer-causing agents, 
or starvation. In these situations, lysosomes 
break down a portion of the cell's contents , 
liberating amino acids that can be used to make 
the most essential substances and ensuring the 
cell's survival without major damage. 
Lysosomal membranes prevent enzymes from 
leaving the organelle, but permit entry of new 
enzymes if they have been properly labeled in 
the Golgi apparatus. However, if a lysosomal 
enzyme is not produced or if an enzyme is not 
properly "addressed" in the Golgi, a lysosomal 
storage disease can result. Persons with the 
lysosomal storage disease known as Hurler's 
syndrome, for example, cannot breakdown 
large molecules of sugar-fat compounds called 
glycosaminoglycans because their lysosomes 
do not contain the enzyme iduronidase. 
Glycosaminoglycans accumulate in the 
lysosomes, swelling them so much that the 
functioning of the entire cell is impaired. 
A particularly severe lysosomal disorder is 
known as l-cell disease. Children born with 
this disease lack the entire range of lysosomal 
enzymes; the enzymes are made, but they are 
dumped outside the cell instead of being sent 
to the lysosomes. Various cellular nutrients 
thus cannot be digested and so pile up in dark 
lumps, called inclusion bodies, within the 
lysosomes. The disease affects the kidneys, 
heart, and nervous system, and children with 
it usually die of heart failure or pneumonia 
before reaching puberty. 
In the early 1 970's, Elizabeth Neufeld, 
who was then at NIH, showed that the 
lysosomal enzymes of persons with l-cell 
disease emerge from the Golgi apparatus 
without the chemical tag they need to be 
directed to the lysosomes. She also showed 
that the defect could be corrected in test-tube 
cultures of cells taken from people with the 
disease. The corrective factors she supplied 
were the specific, properly tagged enzymes 
that the cells lacked. 
Scientists hoped that such "enzyme replace- 
ment therapy" could be used to treat people 
with enzyme disorders. To date, however, it 
has proved difficult to deliver the missing en- 
zymes to the cells that need them and to 
induce the lysosomes in each cell to take up 
the enzymes. When purified enzymes are 
injected directly into the body, they tend to be 
quickly destroyed or inactivated. It is particu- 
larly difficult to get enzymes into the brain — an 
important problem now under investigation, 
since several lysosomal diseases produce 
severe mental retardation. 
In many ways, then, health and disease 
depend on the lysosomal membrane's ability 
to control the uptake and release of its 
contents. Some substances seem to stabilize 
and strengthen the membranous envelope, 
while others weaken it. In the future research- 
ers may find ways to use these properties for 
the prevention of disease or for therapy. 
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