Lipids 4

Question 1

Degradation of Glycolipids

Answer 1

requires sequential action of different glycosidases w/ high substrate specificity–any defect in any single enzyme will result in accumulation of non-degraded material

Question 2

Tay-Sachs

Answer 2

Beta-hexoaminidase A leads to accumulation of Ganglioside Gm2; intellectual disability, blindness, death before 3

Question 3

Gaucher Disease

Answer 3

Beta-glucosidase (beta-cerebrosidase) ; Glucocerebroside; liver and spleen enlargement, erosion of long bones

Question 4

Fabry Disease

Answer 4

alpha-galactosidase; ceramide trihexoside; skin rash and kindey failure

Question 5

Niemann Pick Disease

Answer 5

Sphingomyelinase; sphingomyelin; liver and spleen enlargement, intellectual disability

Question 6

Sandhoff disease

Answer 6

Beta-hexosaminidase A and B; Gm2 ganglioside, globosides; presents like Tay Sachs but progresses more rapidly

Question 7

Metachromatic leukodystrophy

Answer 7

arylsulfatase; sulfatide; intellectual disability

Question 8

Where is cholestersol synthesized? Begins with what substrate?

Answer 8

cytoplasm during well fed state and begins w/ acteoacetyl-CoA (ketone bodies)

Question 9

Cells that produce cholesterol have what enzyme to do this?

Answer 9

HMG-CoA synthase (different isozyme than the one involved in ketone body formation in the mito matrix; keeps both processes separate); acetoacetyl-CoA—> hydroxymethyl-glutaryl-CoA (HMG-CoA);

Question 10

What tissues produce cholesterol?

Answer 10

Liver, intestine, reproductive

Question 11

Rate Limiting Step in Cholesterol synthesis?

Answer 11

HMG-CoA —> Mevalonic acid (HMG-CoA reductase; requires input of 2 NADPH molecules)

Question 12

3 Ways HMG-CoA reductase is regulated? Drug effects?

Answer 12

1. Phophorylation by AMP-dependent kinase (PKA) inactivates the enzyme: HMG-CoA is active when cell energy is high
2. insulin dependent dephosphorylation activates the enzyme: active when blood glucose concentrations are high
3. High cytoplasmic cholesterol concentrations inhibit HMG-CoA reductase: HMG-CoA reductase is active when cellular cholesterol is low
   - –can be inhibited statins

Question 13

Lecitin:Cholesterol acyltransferase (LCAT)

Answer 13

transfers a FA to cholesterol –> cholesterol ester (completely hydrophobic and found only in centers of lipoproteins or in cytosolic fat droplets)

Question 14

Bile Acids

Answer 14

acidic and water soluble; modification of cholesterol; secreted by liver into digestive tract for emulsifying fat