Lysosomal Accumulation of Lipids Flashcards
What do lysosomes do in LDL receptor mediated regulation of cholesterol metabolism?
Lysosomes will degrade LDL and the internalized apo-B100 is degraded to form amino acids. Cholesterol esters will be hydrolyzed to free cholesterol and fatty acids
What happens to cholesterol that has been re-esterified by ACAT?
In extra hepatic cells they form cytosolic droplets and are used for cholesterol storage. In hepatocytes, the cholesterol esters become part of the neutral lipid core within the VLDL particle
What is Niemann-Pick type C disease (NPC)?
An autosomal recessive disease that can have progressive neurological effects, hepatic enlargement and damage.
This occurs because unesterfied cholesterol, sphingomyelin, phospholipids, and glycolipids, especially GM2 will accumulate within the lysosomes of various organs including the liver and spleen
What is filipin?
Filipin is a fluroescent dye that can detect cholesterol accumulation in lysosomes that are in cultured human fibroblasts
What do NPC1 and NPC2 do?
NPC1 gene encodes a membrane protein with 13-16 trans-membrane segments located within the endosomes. NPC2 gene encodes a soluble protein with the endo/lysosomes. Both proteins bind to cholesterol with high affinity
What are the three major cholesterol pools?
- Cholesterol derived from LDL
- Cholesterol synthesized de novo in the ER
- Cholesterol involved in the cholesterol/cholesteryl ester (CE) cycle
What happens when you have Niemann-Pick disease Type A or Type B?
Molecular lesion is at the lysosomal sphingomyelinase, and this causes the accumulation of sphingomyelin in the lysosome
What happens when you have Niemann-Pick type C disease?
Accumulation of sphingomyelin and glycosphingolipids
What are Gangliosides?
They are glycolipids that are concentrated at the outer leaflets of plasma membranes. Participate in a number of signal transduction processes at the cell surface
How are Glycosphingolipids degraded?
They are internalized by endocytosis and then degraded by lysosomes.
What are sphingolipidoses?
They are lipid storage diseases that are a result of sphingolipid accumulating in the lysosomes
What is Tay-Sachs disease?
A disorder of ganglioside degradation. So you are not having adequate degradation of gangliosides. Have elevated gangliosides in the brain of infants.
GM2 accumulates. Mutation in Hex A that converts GM2 to GM3
What mutation do people with Tay-Sach’s disease have?
They have a missing or deficient B-N-acetylhexosaminidase.
