Week 2: Lipids

Question 1

Is esterified or unesterified cholesterol more polar?

Answer 1

unesterified

Question 2

Micelle contents

Answer 2

bile salts

MAGs

FFAs

Phospholipids

Cholesterol

Question 3

How do FFAs and Cho get into intestinal cells?

Answer 3

Short + medium chain FA diffuse

LCFA are transported

Cho is transported

Question 4

What is the calculation for LDL?

Answer 4

LDL= total cho- (HDL Cho + TAG/2.2)

Question 5

What is the major apolipoprotein of:

• chylomicrons
• VLDL
• IDL
• LDL
• HDL

Answer 5

chylomicrons: B48
VLDL:B100
IDL: B100
LDL: B100:
HDL: A

Question 6

Prevalence of familial htz hypercholesterolemia?

E2 homozygosity?

familial combined hyperlipedemia?

Answer 6

1/500 FHH (elevated trigs)

E2: 1%

1/50 FCHL (AD inheritance) (elevated cho + trig)

Question 7

The classes of drugs which have an effect in FH, by in part upregulating LDL receptor activity are known as

Answer 7

statins

bile acid resins

Question 8

What lipid lowering agent is known to increase INR?

Answer 8

cholestyramine

Question 9

Fibrates are PPAR __ activators whereas thializolidinediones are PPAR__ activators

Answer 9

Fibrates: PPAR alpha

Thializidinedione: PPAR gamma

Question 10

What is Apo CIII?

Answer 10

Inhibitor of LPL

Question 11

What is the main outcome of the INTERHEART and JUPITER studies

Answer 11

INTERHEART: identified 9 risk factors for MI

JUPITER: rosuvastatin decreased CVD disease in primary prevention

Question 12

lauric, myrstic, palmitic, stearic are all ____

Answer 12

saturated FAs

Question 13

Describe the hormonal control of lipolysis

Answer 13

Epinephrine, via cAMP

Cortisol, via glucocorticoid receptor

Growth hormone, via ?

Glucagon?

Insulin decreases HSL activation

Question 15

What are some different kinds of lipids?

Answer 15

fatty acids

glycerolipids (MAGs, DAGs, TAGs, etherlipids)

phospholipids

sphingolipids

Question 16

Describe briefly what the intracellular metabolism of lipids looks like?

Answer 16

Steps in metabolism

1. Get into cytosol
   a. FFAs taken up passively (simple diffusion, transport proteins) @ targets
   b. within cytosol, FFAs esterified to CoA and bound to FA binding proteins (cell equivalent of plasma albumin)
2. Get into the mitochondrion
   a. Transported as acyl CoA thru permeable outer mito membrane (OMM)
   b. Coupled to carnitine (via CPT-1) and transported thru IMM as acyl carnitine
   c. Converted back to fatty acyl CoA in mito matrix (via CPT-2)
   **FAs longer than C12 require CPTs for transport (most of dietary FAs > 12 C’s)
3. Oxidize it

• beta oxidation of even numbered FA
• • 3 separate enzymes perform acyl CoA dehydrogenase function
  o short, medium, and long chain deHase
  o **Very long chain FAs are actually metabolized first in peroxisomes
  • deficiencies in these peroxisomal VLCFA enzymes → Adrenoleukodystrophy (also seen in ENDO week 4)

Question 17

What is the defect associated with:

• familial hypercholesterolemia
• familial defective apoB
• PCK9
• familial combined hypercholesterolemia
• familial chylomicronemia
• Tangier
• Familial LCAT deficiency
• Familial CETP deficiency
• Apo E

Answer 17

familial hypercholesterolemia: LDL receptor doesn’t work, high LDL-C, normal trigs

familial defective apoB: apoB can’t bind the LDL receptor, high LDL-C

PCK9: gain of function results in too many LDL receptors being degraded, high LDL-C

familial combined hypercholesterolemia: unknown cause, high trigs and mild high LDL

familial chylomicronemia: LPL deficiency, ApoCII def, anchoring protein deficiency–> high trigs, recurrent pancreatitis

Tangier: ABCA1 gene mutation- cholesterol cannot be mobilized from periphery

Familial LCAT deficiency: low HDL, LCAT need to esterify cho in HDL

Familial CETP deficiency: high HDL..CETP needed to transfer CE between HDL and VLDL. no evidence of cardioprotection

ApoE4: increases cho

ApoE2: can develop dysbetalipoproteinemia

Question 18

Features of dysbetalipoproteinemia. What apoE genotype is associated with this?

Answer 18

• elevated cho, trigs
• palmar xanthomas, tubero-eruptive xanthomas
• premature CAD

1/50 E2 homozygotes get this. the other 49/50 tend to have lower cho. E4 homozygotes tend to have higher cholesterol

Question 19

Clinical features of familial LCAT deficiency

Answer 19

corneal opacity, hemolytic anemia, renal failure

severe HDL deficiency

Question 20

Clinical features of familial chylomicronemia. Prevalence

Answer 20

hepatosplenomegaly, eruptive xanthomas, lipemia retinlalis

severe trig elevateion

1/1 000 000

Question 21

why is lecthin useful clinically

Answer 21

marker of fetal lung development. can use lecthin to sphingomyelin ratio

Question 22

What is Fabry’s disease?

Answer 22

x-linked loss of alpha galactosidase

Question 23

What is the classic lipid profile for someone with metabolic syndrome?

Answer 23

high total, LDLD, trigs

low HDL

high FPG

Question 24

How to diagnose metabolic syndrome

Answer 24

Metabolic Syndrome Dx:
• 3 or more of the following
o waist >102 in men, 88 women
o Trigs >1,7
o HDL <1.0 in men or 1.3 in women
o BP >130/85
o FPG >6.1