Lipid structures and hormonal control

Question 1

Risk factors for CAD (epidemiology)

Answer 1

age - major
male
cigarettes
DM
cholesterol
BP
family history of premature CAD
inflammatory biomarkers
overweight, obesity

Question 2

Pathophysiology evidence for CAD

Answer 2

Vulnerable human atherosclerotic plaque
LDL-C, hypertension, diabetes and smoking lead to endothelial cell dysfunction
- v/c
- increased pltaelet and leukocyte adhesion
- smooth muscel cell migration and growth
-increased lipid deposition with reduced clearance

Question 3

Genetic risk factors for CAD

Answer 3

any that increase LDL-C/TAG

Question 4

Clinical trial evidence for CAD

Answer 4

greater reduction in LDL-C = lowered risk
more effective to treat LDL-C than HTN
secondary prevention more effective

Question 5

Lipid lengths

Answer 5

short: 2-5
Medium: 6-12
Long: 12-18
Very long: >18
each have a unique acyl-CoA dehydrogenase (but overlaps)

Question 6

Essential lipids

Answer 6

linoleic
alpha-linoleic
arachidonic acids

Question 7

Trans fats

Answer 7

arise form partially hydrogenated plant oils, rancid plant oils and ruminant animal fats
effects on lipid: increase LDL, lower HDL

Question 8

Ether glycerolipid structure

Answer 8

Glycerol
C1 - FA (ETHER linkage)
C2 - FA (as above)
C3 - phosphate head group

Question 9

Glycerophospholipid structure

Answer 9

Glycerol + 2 FA side chains (ester linkage) + P-head group

Question 10

Phosphatidylcholine (lecithin)

Answer 10

R1 = long chain, saturated
R2 = long chain, unsaturated
Marker of fetal lung maturity

Question 11

Lecithin: sphingomyelin ratio

Answer 11

L:S >2 mature - neonatal RDS less likely

immature <1.5

Question 12

Phosphatidylethanolamine (cephalin)

Answer 12

usually R1 = stearic acid
R2 = long-chain unsatuated
structural membrane phospholipids, esp in CNS

Question 13

Phosphatidylserine

Answer 13

membrane structural phospholipid

synthesized by headgroup exchange PE + Serine –> PS + ethanolamine

Question 14

Phosphatidylinositol

Answer 14

R1: stearic acid
R2: arachidonic acid
low concentrations in membranes
mediator of intracellular signals

Question 15

Phosphatidylglycerol

Answer 15

major component of mitochondrial membranes

component of pulmonary surfactant - can also be used as a marker for fetal lung maturity

Question 16

Diphosphatidylglycerol

Answer 16

aka DPG, cardiolipins
Component of pulmonary surfactant
recognized by antiphospholipid antibody

Question 17

Sphingolipids structure

Answer 17

all are based on ceramide (with phosphocholine or sugar attached), formed from sphingosine

classes:
phosphosphingolipids
glycosphingolipids

Question 18

Sphingolipid function

Answer 18

intracellular communication
antigenic determinants of ABO blood groups
receptors for certain viruses and bacteria

Question 19

Sphingolipids - disease

Answer 19

metabolic diseases from defects in sphingolipid metabolism - often due to loss of enzymes for modifying sugars:
Tay Sachs
Fabry’s
etc.

Question 20

Fabry’s disease

Answer 20

X-linked recessive, due to loss of alpha-galactosidase A
Lysosomal accumulation of upstream glycosphingolipid
Endothelial swelling and proliferation, disturbances in intraluminal P and angiectasia –> dilated, elongated, distorted vessels –> subject to occlusion
chronic HTN, renal and heart failure
can get stroke

Question 21

Fabry’s disease diagnosis

Answer 21

family history of early stroke in males
pain in distal extremities
multiple angiokeratomas (speedo distribution)
recurrent headaches
HTN
Corneal opacities

Question 22

Fabry’s disease tx

Answer 22

prevent HTN sequelae
decrease possibility of strokes
enzyme replacement therapy

Question 23

Hormones that increase lipolysis

Answer 23

counter regulatory hormones:
epinephrine
glucagon
cortisol
GH

Question 24

Hormones that decrease lipolysis

Answer 24

Insulin: induces phosphorylation and activation of the phosphodiesterase type 3B –> decrease in cAMP –> decrease PKA

Question 25

Epinephrine - effect on lipolysis

Answer 25

immediate increase in lipolysis | cAMP dependent activation of PKA --> phosphorylation and activation of hormone-sensitive lipase

Question 26

GH - effect on lipolysis

Answer 26

overall activates HSL | lipolysis also potentiated via increase sensitivity to catecholamines

Question 27

Infection - risk factor for CAD

Answer 27

C. pneumoniae infection =associated with poor serum lipod profile Infection with parasites/acute bacterial infection also associated with poor lipid profile

Question 28

Air pollution - CAD

Answer 28

ultra-fine particles in air combined with LDL --> accelerate narrowing and blockage of blood vessels Air pollution + LDL work together to activate the genes that promote cellular inflammation

Question 29

CPT deficiency

Answer 29

required for transport of FAs >12 recurrent attacks of myoglobinuria and rhabdomyolysis muscle pain, stiffness, and tenderness triggered by exercise and fasting severe - fatal in infancy

Question 30

Very long-chain fatty acid metabolism

Answer 30

Peroxisomal first | then mitochondrial

Question 31

Acyl carnitine profiling

Answer 31

for MCAD deficiency C8/C10 ratio newborn screening

Question 32

X-linked ALD

Answer 32

 in the cerebral form of X-ALD, early development is normal  first neurological manifestation commonly between ages 4 and 8.  impaired auditory discrimination, visual disturbances, signs of dementia, spatial disorientation, poor coordination, seizures – due to CNS demyelination  vegetative state within 2 years and then death  patients are frequently hypocortisolemic – for some this is the only manifestation!  some idiopathic Addison’s disease is actually due to ALD!