Lysosomes and Peroxisomes

Lysosomes

Lysosomes are roughly spherical bodies bounded by a single membrane. They are manufactured by the Golgi apparatus (pathway 2 in the figure).

• proteases
• nucleases
• polysaccharidases

The pH within the lysosome is about pH 5, substantially less than that of the cytosol (~pH 7.2). All the enzymes in the lysosome work best at an acid pH. This reduces the risk of their digesting their own cell if they should escape from the lysosome.

Materials within the cell scheduled for digestion are first deposited within lysosomes. These may be:

• other organelles such as mitochondria that have ceased functioning properly
• food molecules or, in some cases, food particles taken into the cell by endocytosis
• foreign particles like bacteria that are engulfed by neutrophils

  Some tricks that intracellular parasites use to avoid destruction by lysosomes.

• antigens that are taken up by the "professional" antigen-presenting cells
  • macrophages (by phagocytosis) and
  • B-cells (by binding to their antigen receptors (BCRs) followed by receptor-mediated endocytosis.

  Link to discussion of how antigens are taken up by macrophages and B cells and degraded in their lysosomes.

Lysosomes repair wounds in the plasma membrane.

The exocytosis of lysosomes provides the additional membrane needed to quickly seal wounds in the plasma membrane.

Peroxisomes

Peroxisomes are about the size of lysosomes (0.5-1.5 µm) and like them are bound by a single membrane.

They also resemble lysosomes in being filled with enzymes.

The enzymes and other proteins destined for peroxisomes are synthesized in the cytosol. Each contains a peroxisomal targeting signal (PTS) that binds to a receptor molecule that takes the protein into the peroxisome and then returns for another load.

Two peroxisomal targeting signals have been identified:

• a 9-amino acid sequence at the N-terminal of the protein;
• a tripeptide at the C-terminal.

Some of the functions of the peroxisomes in the human liver:

• Breakdown (by oxidation) of excess fatty acids.
• Breakdown of hydrogen peroxide (H₂O₂), a potentially dangerous product of fatty-acid oxidation. It is catalysed by the enzyme catalase.
• Participates in the synthesis of cholesterol. One of the enzymes involved, HMG-CoA reductase, is the target of the popular cholesterol-lowering "statins".
• Participates in the synthesis of bile acids.
• Participates in the synthesis of the lipids used to make myelin.
• Breakdown of excess purines (AMP, GMP) to uric acid (which can lead to gout).

Peroxisome Disorders

• Most involve mutant versions of one or another of the enzymes found within peroxisomes.

  Example: X-linked adrenoleukodystrophy (X-ALD). This disorder results from a failure to metabolize fatty acids properly. One result is deterioration of the myelin sheaths of neurons. The disorder occurs in young boys because the gene is X-linked. An attempt to find an effective treatment was the subject of the 1992 film Lorenzo's Oil.

• A few diseases result from failure to produce functional peroxisomes.

  Example: Zellweger syndrome. This disorder results from the inheritance of two mutant genes for one of the receptors (PXR1) needed to import proteins into the peroxisome.

Peroxisomes are also called microbodies.