Eicosanoids- Brar

Question 1

What are eicosanoids?

Answer 1

Prostaglandins (PG), Thromboxanes (TX) and Leukotrienes (LT)

Question 2

What is the main precursor to PGs? How are they generated? How do PGs exert their effect?

Answer 2

aracidonic acid (from linoleic acid)
Generated by COX-1 and COX-2 (inducable, responde to immune and inflammatory signals)
PGs function like autocrine or paracrine hormones

Question 3

What is sphingolipidosis? What tissue is most affected? What is the inheritance pattern?

Answer 3

• Sphingolipids are degraded in lysosomes
• Deficiency of degradation enzymes leads to accumulation of certain sphingolipids in the lysosome
• Enzyme deficiency is expressed in all tissues
• Complete deficiency leads to severe disease
• Nervous tissue most affected because of its high sphingolipid content and turnover
• Inheritance is autosomal recessive except for Fabry disease (which is X linked recessive)

Question 4

What are the common sphingolipid disorders (7) and the enzyme affected?

Answer 4

1. Gm1 Gangliosidosis (β-Galactosidase)
2. Tay-Sachs (β-Hexosaminidase A (α subunit))
3. Sandhoff (β-Hexosaminidase A (β subunit) and B)
4. Fabry (x-linked) (α-Galactosidase)
5. Gaucher (β-glucosidase (glucocerebrosidase))
6. Niemann-Pick (A + B) (Sphingomyelinase)
7. Metachromatic Leukodystrophy (Arylsulfatase A)
8. Krabbe (Globoid cell leukodystrophy)(β- Galactosidase (galactocerebrosidase))
9. Farber (Ceraminidase)