Glycosylation and Lysosomal Storage Diseases

Flashcards covering the biochemical process of lysosomal protein tagging and the various lysosomal storage diseases resulting from terminal glycosylation errors.

GlcNAc (N-acetylglucosamine)

A sugar component of the prebuilt oligosaccharide, referred to in the text as "yellow dots" or "Glipknak," which is involved in tagging proteins for the lysosome.

$$Mannose-6-phosphate \text{ (M6P)}$$

The specific chemical tag added to mannoses on a protein within the Golgi that signals for the protein to be transported to the lysosome.

$$UDP \text{-N-acetylglucosamine}$$

A nucleotide-type structure used by enzymes to provide the phosphate and $GlcNAc$ group during the first step of lysosomal tagging.

$$GNPTAB$$

The gene/enzyme responsible for Step 1 of the lysosomal tagging process, which adds phosphorylated $GlcNAc$ onto mannose; its deficiency leads to ML2.

M6P Receptor

An internal receptor in the Golgi that binds to $Mannose-6-phosphate$ labeled proteins to cluster them into transport vesicles.

Sorting Vesicle (Recycling Endosome)

A structure where the $M6P$ receptor is separated from its ligand; the receptors are then recycled back to the Golgi while the proteins proceed to the lysosome.

CURL

An older acronym standing for Compartment of Uncoupling Receptor and Ligand, referring to the sorting vesicle or recycling endosome.

Mucolipidosis Type 2 (ML2)

Also known as I-cell disease or Leroy disease, an autosomal recessive disorder caused by a lack of the enzyme in Step 1 of the $M6P$ tagging process.

I-cell

In the context of ML2, the 'I' stands for 'inclusions,' referring to fibroblasts and connective tissues stuffed with unprocessed material that the lysosomes failed to break down.

Hurler Syndrome (ML1)

A member of the lysosomal storage disease family, categorized as Mucolipidosis Type 1.

Pseudohurler (ML3)

A lysosomal storage disease categorized as Mucolipidosis Type 3, related to ML2 but generally less severe.

Tay Sachs Disease

A well-known and currently manageable example of a lysosomal storage disease.

Niemann Pick Disease (NPC)

A cholesterol storage disease that primarily affects neurons, leading to a decline in motor function and potential spontaneous self-mutilation.

Cyclodextrin

The active ingredient in Febreze, used as a therapy for Niemann Pick disease to cage and clear cholesterol from cells.