Lipid Mobilization and Catabolism

Question 1

What is the difference between hormone-sensitive lipase and LPL?

Answer 1

Lipogenesys vs lipolysis

• LPL: metabolism of Lipoproteins (chylo and VLDL). (+) ⬆️ insulin and Apo CII. Surface of capillary endothelium (direct contact with the blood) adipose and muscle. Hydrolyzes FA from TG
• HSL: hydrolyzes TG inside adipose. (+) ⬇️ insulin, ⬆️ epinephrine and cortisol (no glucagon).

Question 2

What mechanism allow long-chain FA enter to mitochondria to beta-oxidation?

Answer 2

Carnitine transport system:

• CAT 1 (carnitine acyltransferase-1) transfer fatty acyl group to a carnitine (outer membrane)
• Fatty acylcarnitine pass the inner membrane by carnitine shuttle
• CAT 2 transfer fatty acyl group back to CoA (mitochondrial matrix)

Question 3

What regulates the CAT 1 directly and indirectly?

Answer 3

• (-) by Malonyl CoA (coming from FA synthesis)
• (-) insulin ▶️ 🔛 acetyl CoA carboxylase (⬆️ Malonyl CoA)
• (+) glucagon ▶️ ⬇️ Malonyl CoA

Question 4

What suggest a severe hypoglycemia and absence of ketosis? What can precipitate it?

Answer 4

MCAD deficiency

• block the beta oxidation, hypoglycemia (lack ATP to gluconeo), no KB (⬇️ acetyl CoA)
• precipitate by fatty meals, metabolic stress (severe fasting, exercise, infections)

Question 5

Why is produced dicarboxilic aciduria in MCAD deficiency?

Answer 5

• peroxisomes make w-oxidation ▶️ dicarboxilic acid

* cause deficiency (mitochondria can’t) look for some where to oxidate the less 20C FA

Question 6

What is the most common tissue affected by CAT-2 deficiency? Symptoms

Answer 6

• muscle (mitochondria) - myopathic form adolescent of adult onset
• aches, weakness, myoglobinuria, rhabdomyolysis; muscle Bx: ⬆️ TG as lipid droplets in cytoplasm

Question 7

What are the requirements for the two enzymes of the propionic pathway? Which are they?

Answer 7

• Propionyl CoA carboxylase: biotine, co2, ATP

- methylmalonyl CoA mutase: Vit B12

Question 8

What differentiates the vitamin deficiency (folate or B12) in megaloblastic anemia and why?

Answer 8

• excretion of acid methylmalonic acid (methylmalonic aciduria) ▶️ Vit B12 deficiency
• Vit B12 def ▶️ 🔚 methylmalonyl CoA mutase
  1. Accumulation aberrant FA in myelin sheet ▶️ peripheral neuropathy
  2. ⬆️⬆️ methylmalonyl excretion

Question 8

What tissues firstly use the ketone bodies as a source of fuel?

Answer 8

Cardiac and skeletal muscle, renal cortex

Question 9

Since what moment does the brain begin to use the ketone bodies?

Answer 9

After a week of fasting approximately

Question 10

Why the liver can not use or metabolize ketone bodies?

Answer 10

Doesn’t have thiophorase

Question 11

In pathologogic ketosis (ketoacidosis), how are the laboratory measurements? What ketone body predominate?

Answer 11

• Ratio between acetoacetate/B-hydroxybutyrate shift. B-hydroxybutyrate predominates (B-hydroxybutyrate should be measured)

Question 12

What differentiate Fabry disease of the others sphingolipidoses?

Answer 12

Fabry is the only X-linked recessive (Alfa galatosidase deficiency), accumulates ceramide trihexoside in lysosomes.

Question 13

Where are the glucocerebrosides come from?

Answer 13

• brain: turnover of gangliosides during brain development and myelin sheath
• other: breakdown of old RBC and WBC

Question 14

How can you differentiate Gaucher vs Niemann-Pick disease, what do they have in common?

Answer 14

Common: lipid-laden macrophages (Gaucher cells - like crumpled tissue paper), Hepatosplenomegaly
Difference: Gaucher - bones: erosion, fractures, pancytopenia.

Question 15

How do you differentiate Niemann-Pick vs Tay-Sachs diseases? what do they have in common?

Answer 15

Common: cherry-red spot in macula
Difference: Tay-sachs: NO Hepatosplenomegaly