Sphingolipidosis Flashcards
Where are ethanolamine plasmogens found?
myelin
Where are choline plasmalogens found?
cardiac muscle
Where does plasmogen synthesis occur?
in peroxisomes
What are plasmogens derived from?
dihydroxyacetone phosphate
What do phospholipids located in the cell membrane or in lysosomes do?
they degrade glycerophospholipids
what does phospholipase A1 do?
it removes fatty acyl group on C1 of the glycerol backbone
what does phospholipase A2 do?
it removes fatty acyl group on C2 of the glycerol backbone
what does phospholipase C do?
it cleaves the bond joining C3 of glycerol moiety to phosphate
What are shingolipids formed from?
ceramide
Where and how is ceramide synthesized?
in the ER by condensation of serine and palmitoyl CoA
What do sphingolipids do?
they serve in intracellular communication and as antigenic determinant of the ABO blood groups
What are sphingolipids degraded by?
lysosomal enzymes
What is the mode of inheritance for most sphingolipidoses?
autosomal recessive
What are 4 constant features that are exhibited in these disorders?
- ceramide accumulation in cells, particularly neurons
- rate of synthesis of stored lipid is normal
- enzymatic defect is in the lysosomal degradation pathway of sphingolipds
- the extent to which the activity of the affected enzyme is decreased is similar in all tissues
(1) autosomal recessive
(2) Defective Hexosaminidase A by mutation in HexA gene
(3) accumulation of ganglioside GM2
(4) common in Ashkenazi Jews
(5) progressive destruction of nerve cells in the brain and spinal cord, muscle atrophy, cherry red spot in retinoscopy, blind, deaf, unable to swallow
Tay-Sach’s Disease
Without the alpha subunit, what happens with the beta subunit in Tay-Sachs Disease?
it can form active tetramers, named hexosaminidase B, which cleaves the glycolipid globoside., thus ganglioside GM@, but not globoside accumulates
(1) autosomal recessive
(2) mutation in HexB gene
(3) inactivation of both hexosaminidase A and B
(4) accumulation of GM2 and globoside in the lysosomes
(5) mental retardation, blindness, muscular weakness
Sandhofff Disease
(1) defective or absence of Sandhoff activator protein (required by hexosaminidase A)
(2) accumulation of GM2 ganglioside
(3) mental retardation, blindness, muscular weakness
Sandhoff Activator Disease
(1) X-linked recessive
(2) deficiency of alpha-Galactosidase
(3) accumulation of globotriaosylceramide/ceramide trihexoside
(4) skin rash (angiokeratomas), kidney failure, cardiac complications, hypertension, cardiomyopathy
(5) Fabry crises: episodes of intesnse, excruciating burning pain felt initially in hands and feet, radiating to other parts of the body
Fabry’s Disease
(1) autosomal recessive
(2) deficiency of glucocerebrosidase (beta-glucosidase)
(3) accumulation of glucocerebrosides in WBC, spleen, liver, kidney, lung, brain and bone marrow
(4) hepatosplenomegaly, anemia, thrombocytopenia, leukopenia, easily bruised, convulsions, hypertonia, dementia, ocular muscle apraxia
(5) “wrinkled tissue paper” looking cytoplasm of gaucher cells
Gaucher’s Disease
(1) autosomal recessive
(2) complete absence of sphingomyelinase enzyme
(3) accumulation of sphingomyelin
(4) hepatosplenomegaly, ataxia, dysarthria, dysphagia, dystonia, supranuclear gaze palsy, dementia, seizures, cherry red spot retinoscopy, foam cells
Niemann-Pick Disease
(1) autosomal recessive
(2) deficiency of ceramidase
(3) accumulation of ceramide in joints, CNS, throat, liver and other tissues
(4) subcutaneous nodules, tissue granulomas, joint pain, joint swelling, hoarseness of voice
Farber Disease
What intermediates in glycolysis are important connections in carbohydrate and lipid metabolism?
glycerol phosphate and dihydroxyacetone phosphate (DHAP)
