Lysosome

Lysosomes are membrane enclosed compartments filled with acid hydrolytic enzymes. A H⁺ pump in the lysosomal membrane uses the energy of ATP hydrolysis to pump H⁺ into the lysosome thereby maintaining the lumen at its acidic pH of about 5.0.

Digestive enzymes are delivered to lysosomes via the Golgi apparatus. Substances to be digested come from endocytosis.

Delivery of hydrolases and membrane proteins: are synthesized in the rough ER and transported through the Golgi apparatus to transport vesicles that deliver these proteins to late endosomes (which will form lysosomes). Lysosomal hydrolases have a unique marker in the form of mannose 6-phosphate (M6P) groups which are added exclusively to the N-linked olgiosaccharides of these enzymes as they pass through the lumen of the cis Golgi. 2 enzymes are responsible for adding the M6P groups and these enzymes recognize the hydrolase proteins due to a signal patch on the polypeptide surface of the hydrolase.

The M6P groups are recognized by transmembrane M6P receptor proteins which are present in the trans Golgi which aid in packaging the hydrolases into clathrin coated vesicles that bud from the trans Golgi. The receptor travels with the vesicle to a late endosome where the hydrolase dissociates from the receptor due to the lower pH in the endosome. The receptor is then returned to the golgi in a vesicle where it can be reused.

Sources of substances to be digested: 1) endocytosis is the process by which cells take up macromolecules. 2 types of endocytosis are distinguished based on the size of the endocytic vesicles formed.  Phagocytosis involves the ingestion of large particles such as microorganisms or dead cells via phagosomes and pinocytosis involves the ingestion of solutes via small pinocytic vesicles. In mammals, 3 types of white blood cells are phagocytes; macrophages, neutrophils and dendritic cells. Eucarytoic cells continually ingest parts of their plasma membrane in the form of small pinocytic (endocytic) vesicles. The same amount of membrane removed is restored through the process of exocytosis. Pincocytic vesicles are typically clathrin coated although they may also be caveolae.

Many cell surface receptors that bind specific extracellular macromolecules become localized in clathrin coated pits in a process called receptor mediated endocytosis. (examples include LDL receptors) The coated endocytic veiscles rapidly shed their clathrin coats and fuse with early endosomes. Most of the ligands dissociate from their receptors in the acidic environment of the endosome and end up in lysosomes while most of the receptors are recycled back to the cell surface but sometimes both the receptor and ligand end up being degraded in lysosomes, resulting in receptor down regulation. In some cases, both are transferred to a different plasma membrane and the ligand is thereby released by exocytosis at a surface of the cell different from that where it started in a process called transcytosis.

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