46. TG and complex lipids

Question 1

TG synthesis

Answer 1

Glycerol-3P comes from gluconeogenesis and DHAP.
G3P + 2 fatty acyl CoA –> phosphatidic acid
Phosphatidic acid + fatty acyl CoA –> TG

Question 2

Phosphatidyl compounds

Answer 2

Diacylglycerol + alchol (polar head)
CDP-diacylglycerol + alcohol (glycerol or inositol)
diacylglycerol + CDP-alcohol (choline or ethinoamine)

Question 3

Phospholipidases - A2

Answer 3

Cuts off middle fatty acid –> releases arachidonic acid.
Activated by trypsin in pancreatic juice.
Inhibited by glucocorticoids.

Question 4

Phospholipidases - C

Answer 4

cuts off phophate group on polar head.

In liver, activated by PIP2 system to release IP3 and diacylglycerol. Both are signaling molecules.

Question 5

Sphingolipids

Answer 5

amphipathic compounds, most commonly found in NS.

Question 6

Sphingolipids synthesis

Answer 6

Palmitoyl CoA + serine –> ceremides
Ceremide + cholind phosphate –> sphinomyelin.
Ceremide + UDP-gal/glu –>gal/glucocerebrosides.
Ceremide + multiple sugar –> globosides.
Globoside + CMP-NANA –> gangliosides.

Question 7

Degradation of Sphingolipid and diseases

Answer 7

1. Tay-Sachs
2. Gaucher
3. Neimann-Pick
4. GM1 gangliosidosis
5. Sandhoff’s
6. Fabry
7. Farber
8. Metachromatic leukodystrophy
9. Krabbe (globoid cell leukodystrophy)

Question 8

Tay-Sachs disease

Answer 8

Defect in beta-hexosaminidase A.
Accumulation of gangliosides.
Rapid neurodegeneration, cherry-red macule, blindness, CNS sx.

Question 9

Gaucher disease

Answer 9

defect in beta-glucosidase.
Accumulation of glucocerebrosides.
Most common lysosomal disease (type I for Ashkenazi Jews).
HSN, osteoporosis of long bones, CNS in rare infantile/juvenile form.

Question 10

Neimann-Pick disease

Answer 10

Defect in sphingomyelinase.
Accum. of spingomyelins.
HSM, neurodegeneration in Type I.