Lipids

Question 1

Why are lipids important?

Answer 1

• Cell membrane constituents
• Absorption of fat-soluble vitamins
• Maintain membrane fluidity
• Thermal insulator and cellular metabolic regulator
• Hormone synthesis
• Organ padding
• Transporters

Question 2

Lipids are mostly made from which source? Exceptions?

Answer 2

• Mostly made from carb sources
• Except essential FAs must be eaten (found in plants)

Question 3

How many esterified FAs does a triglyceride have?

Answer 3

3

Question 4

Saturated fats

Answer 4

• NO bends in structure, pack tightly
• Solid at RT
• Animal sources
• Neutral charge

Question 5

Unsaturated fats

Answer 5

• Bends in structure, don’t pack tightly
• Oil at RT
• Plant sources
• Neutral charge

Question 6

Phospholipids

Answer 6

• Hydrophilic head group and hydrophobic tails
• Amphipathic (hydrophilic/hydrophobic)
• Synthesized in all organs, esp liver

Question 6

Cholesterol

Answer 6

• Unsaturated steroid alcohol
• Amphipathic
• Animal sources
• Plants - phytosterols
• Synthesized in most tissues
• Not readily catabolized
• Small amt used for Vit D

Question 6

Use of bile acid (cholic acid)?

Answer 6

Detergent to allow fat to be taken up and used

Question 7

General lipoprotein structure + function

Answer 7

• Spherical
• Size: 10 nm to more than 1 micron
• Protein + lipids present
• Function: Deliver fuel

Question 8

Lipoproteins Apo A1 and Apo A2 are exclusively found where?

Answer 8

HDL

Question 9

Lipoprotein Apo B 100 is exclusively found where?

Answer 9

LDL

Question 10

Lipoprotein Apo B48 is exclusively found where?

Answer 10

Chylomicrons

Question 11

Lipoprotein Apo(a) is exclusively found where?

Answer 11

Lipoprotein A

Question 12

Function of apolipoproteins

Answer 12

Structural integrity and ligands

Question 13

Chylomicrons
Made when?
Produced by?
Function?
How size affects plasma?
Hydrophobic core composition?

Answer 13

• Made when we eat triglycerides
• Produced by intestine
• Functions to transport exogenous triglycerides (ones we eat) to the liver
• Big so cause turbid/milky appearance of plasma, reflect lots of light
• Hydrophobic core composition: 84% triglyceride + 7% cholesteryl esters

Question 14

VLDL
Produced by?
Function?
How size affects plasma?
Hydrophobic core composition?

Answer 14

• Produced by liver
• Functions to transport endogenous (hepatic-derived) triglycerides, mostly during fasting
• Smaller than chylos, can cause some turbidity but not as buoyant so won’t float on top. Account for most turbidity during fasting hyperlipidemic plasma samples
• Core comp: 65% triglycerides, 8% cholesteryl esters

Question 15

LDL
Produced by?
Function?
How size affects plasma?
Hydrophobic core composition?

Answer 15

• Produced from lipolysis of VLDL in blood circulation
• Function not given, but it gets uptaken by cells via LDL receptor and can cause foamy macrophages. LDL can build up on vessel wall and cause plaques. Macrophages come to clean them up
• Super small so can go to extracellular space of vessel wall
• More cholesteryl ester than triglyceride. Most cholesterol rich particle

Question 16

HDL
Produced by?
Function?
Hydrophobic core composition?

Answer 16

• Produced by liver and intestine
• Functions to reverse cholesterol transport/remove LDL in arteries bc LDL irritates arteries
• More cholesteryl ester than triglyceride

Question 17

Lipoprotein (a)
Similar to which particle?
Elevate levels increase risk of?
Used for what?

Answer 17

• LDL-like particles
• Elevated levels increase risk of premature congenital heart disease (CHD) and stroke
• Used to stratify risk in family history of CHD

Question 18

Intermediate-Density Lipoproteins (ILDLs)

Answer 18

• Normally only transiently present between VLDL->LDL conversion
• Elevated in rare inborn metabolic errors

Question 19

Lipoprotein X

Answer 19

Abnormal lipoprotein found in patients with biliary cirrhosis or cholestasis

Question 20

Name the 4 major pathways of lipoprotein metabolism

Answer 20

1. Absorption
2. Exogenous
3. Endogenous
4. Reverse cholesterol pathway

Pathways 1-3 transport lipids to peripheral cells.
Pathway 4 tries to ta

Question 21

Lipid absorption pathway during digestion

Answer 21

• Pancreatic lipase converts dietary lipids into more polar compounds with amphipathic properties by cleaving off fatty acids
• Triglycerides -> mono/diglycerides
• Cholesterol esters - free cholesterol
• Phospholipids -> lysophospholipids

Question 22

Exogenous pathway

Answer 22

• Chylomicrons initially go to lacteals (small intestine lymph vessels) and then to lymphatic ducts, eventually entering circ by thoracic duct
• Apo C2 is a key protein in triglyceride metabolism, which is found on VLDL and critical to the activation of LPL
• In liver, lysosomal enzymes break down fat and release free FAs, free cholesterol, and aa

Question 23

Endogenous pathway

Answer 23

- Most triglycerides packaged into VLDL are derived from diet and small fraction is made de novo in liver from dietary carbs - IDL taken up by liver via **Apo E** and LDL receptor - IDL triglycerides removed by **hepatic triglyceride lipase** on hepatic endothelial cells, thus making **LDL** - LDL receptor abnormalities -> LDL elevation in blood -> **hypercholesterolemia + premature artherosclerosis**

Question 24

Reverse cholesterol transport pathway

Answer 24

- HDL-mediated - HDL maintains cholesterol equilibrium by removing excess cholesterol from cells

Question 25

National cholesterol education program recommendation

Answer 25

Adults 20+ years have fasting lipoprotein profile performed once every 5 years (total chol, LDL-C, HDL-C, triglycerides)

Question 26

Dyslipidemia in children 9-11 y/o

Answer 26

Abnormally low HDL-C or elevated non-HDL-C

Question 27

Arteriosclerosis definition

Answer 27

Group of conditions that thickens arteries

Question 28

Artherosclerosis definition

Answer 28

Specific type of arteriosclerosis

Question 29

**Arteriosclerosis** Cause? General mechanism? Diagnostic lab eval?

Answer 29

- Deposition of lipids, mainly esterified cholesterol causes heart disease/dyslipidemia - Repeated cell injury -> plaques -> infiltration/cell proliferation to repair the site - LDL central role in initiating/promoting plaque formation - Key to do full lipid panel (total chol, HDL-C, LDL-C, and triglycerides)

Question 30

Dyslipidemia two categories

Answer 30

1. Hyperlipoproteinemia 2. Hypolipoproteinemia

Question 31

Hypercholesterolemia

Answer 31

- Strong correlation btwn **hypercholesterolemia** and **heart disease** mortality - Familal hypercholesterolemia is genetically increased cholesterol levels

Question 32

Hypertriglyceridemia

Answer 32

- 150-200 mg/dL = borderline high trig - Influenced by insulin, glucagon, pituitary growth hormone, ACTH, thryotropin, epinephrine, and norepinephrine - Treat through diet change, fish oil, and/or trig-lowering drugs

Question 33

Combined hyperlipidemia

Answer 33

Elevated serum levels of total cholesterol and trig

Question 34

Lp(a) elevation

Answer 34

- Elevated serum Lp(a) levels, esp in conjunction with LDL elevation - Increased risk of CHD and CVD

Question 35

Non-HDL cholesterol

Answer 35

Elevated levels associated with increased CVD risk even if LDL-C levels are normal

Question 36

Triglyceride measurement

Answer 36

- Lipases cleave fatty acids and free glycerol to participate in one of many enzymatic sequences - Second sequence: **glycerol kinase** and **glycerophosphate oxidase** coupled to same peroxidase **color rxn**

Question 37

HDL methods

Answer 37

- HDL used to be chemically ppt to separate out - Replaced with new class of direct/homogenous methods - automate quantification (**can lack specificity for HDL in unusual specimens**)

Question 38

LDL methods + calculation

Answer 38

Calculate using **Friedewald eqn** *LDL-C = Total chol - HDL - (Trig/5)*