Lipid Transport

Question 1

What is the structure of a lipoprotein?

Answer 1

Hydrophobic core with triglycerides, cholesteryl esters

Surrounded with single-layer membrane with charges on outside that interact with aq surroundings

Proteins embedded in surface membrane

Question 2

What proteins are embedded in surface membrane of lipoproteins?

Answer 2

Apo-proteins - for structural support and for interactions with receptors and catalytic proteins

Question 3

Describe the transport of lipids with albumin

Answer 3

Free fatty acids are released from adipose tissue followed by wave of ketones

Neither require special transport and just bind to hydrophobic pockets on albumin while ketone bodies dissolve readily in serum

Question 4

Describe the transport of lipids with lipoproteins

Answer 4

Lipid transport from enterocytes and liver require lipoproteins.

Triglycerides/cholesterol are released by enterocytes and liver and are loaded into lipoproteins through hydrophobic interactions. Amphipathic FA are converted to hydrophobic TG, cholesterol esterified to cholesteryl esters.

TG and CE form the hydrophobic core of lipoproteins and are shielded from hydrophilic environment

Question 5

How are lipids unloaded from the lipoprotein?

Answer 5

Hydrolysis of TG by lipoprotein lipase releases FA

Hydrolysis of Cholestryl esters by cholesterol esterase releases cholesterol

Question 6

What are the three routes of lipoprotein lipid traffic?

Answer 6

1. Distribution of dietary lipids via chylomicron
2. Distribution of lipids made by the liver: VLDL -> IDL -> LDL
3. Transport of cholesterol to the liver for excretion: HDL

Question 7

What creates serum turbidity after a meal?

Answer 7

Chylomicrons. They are the largest lipoproteins

Question 8

Describe the distribution of dietary lipids

Answer 8

Lipids absorbed by the diet are packed into chylomicrons by enterocytes.

Chylomicrons deliver TG to muscles for consumptions and adipose tissue for storage

Question 9

Describe the distribution of lipids made in the liver

Answer 9

Liver synthesizes lipids in the fed state and packs them into very low density lipoproteins (VLDL)

VLDLs distribute lipids to muscles and adipose tissue and get smaller and denser, turning into intermediate density lipoproteins (IDL) and low density lipoproteins (LDL)

Question 10

When are VLDLs made?

Answer 10

Synthesized during fasting state to be used in fed state

Question 11

Describe the transport of cholesterol to the liver for excretion

Answer 11

Liver synthesizes empty high density lipoproteins (HDL) that absorb cholesterol from peripheral tissues and transport it back to the liver for excretion

Question 12

What is the triglyceride and cholesterol content of lipoproteins?

Answer 12

Chylomicrons - mostly TG (99%)

VLDL - contain TG and some cholesterol (92% TG and 8% chol)

IDL - 85% TG, 15% chol

LDL - 80% TG, 20% chol

HDL - mostly cholesterol, 50% TG, 50% chol

Question 13

What occurs with defects in lipoprotein synthesis?

Answer 13

Hypolipidemia

Question 14

What occurs with defects in lipoprotein unloading?

Answer 14

Hyperlipidemia

Question 15

What are characteristics of hyperlipidemia?

Answer 15

Elevated TG and/or cholesterol

Risk for cardiovascular disease

Question 16

What is primary dyslipidemia?

Answer 16

Abnormal concentration of serum lipids. Congenital disorders caused by mutations in lipoprotein metabolism.

Most frequent cause of dyslipidemia in children and often dominant mode of inheritance where a parent is affected

Question 17

What are apoproteins?

Answer 17

Proteins in the outer membrane of lipoproteins that support structure and regulate function of the lipoprotein

Question 18

What are the apoproteins for structural support?

Answer 18

ApoB48 - in Chylomicrons
ApoB100 - in VLDL, IDL, LDL
ApoA - in HDL

Interact with receptors on the surface of target cells

ApoB100 and ApoB48 are encoded by same gene - variation created by RNA editing

Question 19

What apoprotein regulates fatty acid release from lipoproteins?

Answer 19

ApoC-II

Activates lipoprotein lipase on endothelial cells

Question 20

What apoprotein regulates cholesterol entry into lipoproteins?

Answer 20

ApoA

Activates Lecithin-Cholesterol Acyltransferase (LCAT) for esterification of cholesterol

Question 21

What apoprotein helps with interaction with lipoprotein receptors?

Answer 21

ApoE

A ligand for LDL and scavenger clearance

Question 22

Describe chylomicrons, their apoproteins, and their development

Answer 22

Synthesized in enterocytes and transport lipids from diet. They get smaller as they lose lipids and turn into chylomicron remnants

Apoproteins - ApoB48, ApoC-II, and ApoE

Question 23

Describe VLDL, their apoproteins, and their development

Answer 23

Synthesized in liver and transports fat and cholesterol from metabolic overflow. Get smaller and heavier as they lose fat and pick up cholesterol, converting to IDL and LDL

Lose ApoCII and then ApoE during transition

Apoproteins - ApoB-100. ApoC-II, ApoE

Question 24

Describe HDL, their apoproteins, and their development

Answer 24

Synthesized in liver. Transports cholesterol from body back to liver and get bigger and heavier as they pick up cholesterol. Distribute ApoE and ApoC-II

Apoproteins - ApoA, ApoC-II, ApoE

Question 25

Describe Lipoprotein A, their apoproteins, and their development

Answer 25

Function is unclear but is associated with cardiovascular risk Apoproteins - ApoA-S-S-ApoB100

Question 26

Describe the maturation of chylomicrons

Answer 26

Chylomicrons transport lipids from enterocytes around body and begin as non-functional particles filled with TG from the diet Structural support provided by ApoB-48 After release from enterocytes, chylomicrons obtain ApoC-II and ApoE from HDL Chylomicrons shrink as they lose lipids (lipoprotein lipase action) and turn to remnants Chylomicron remnants bind to liver receptors through ApoE interactions and are removed via endocytosis

Question 27

What has to happen to TG before they can enter enterocytes?

Answer 27

TG has to be hydrolyzed by pancreatic lipase

Question 28

Describe the maturation of VLDL

Answer 28

Liver produces VLDL for fat distribution. Made during fasting and used in fed state VLDL begins as non-functional particle filled with lipids and cholesterol with structural support provided by ApoB-100 VLDL pick up ApoC-II and ApoE from HDL Lose TG through lipoprotein lipase and gain cholesterol by transfer with HDL Transitions to IDL as it loses ApoC-II along with most of its TGs. Becomes LDL as IDL accumulates cholesteryl esters and lose ApoE LDL binds to LDL receptors to clear contents into cholesterol requiring cells

Question 29

What occurs if LDL accumulates?

Answer 29

Surplus LDL either due to overproduction or insufficient clearance, get oxidized and taken up via scavenger receptors which leads to plaque formation in blood vessels

Question 30

Describe maturation of HDLs

Answer 30

HDLs begin in liver as empty particles assembled with ApoA scaffold Deliver ApoC-II and ApoE to maturing chylomicrons and VLDL. Extract cholesterol from membrane and move to liver for excretion Cholesterol extraction from plasma membranes through ABCA1 and transfer to surface of HD: with lipoprotein collides with membrane HDL exchanges cholesteryl esters with LDL through CETP Esterification of cholesterol through LCAT moves cholesterol into HDL for transport to liver where it is converted to bile salt and excreted in feces through bile duct

Question 31

What is secondary dyslipidemia?

Answer 31

Consequences of other metabolic disorders and disturbances Most frequent cause of dyslipidemia in adults Often caused by poor diet, diabetes, alcohol use

Question 32

Fredrickson Phenotypes

Answer 32

Classify dyslipidemia. Incudes 5 classes and allows us to identify the defective component based on observed elevation of serum cholesterol and TG Elevated lipid fraction clues to lipoprotein

Question 33

How does a patient with Fredrickson IIa present?

Answer 33

High LDL High cholesterol Family history of hypercholesterlemia Physical examination shows fatty deposits on Achilles tendons and knuckles Labs shows elevated cholesterol and normal TG

Question 34

What are possible reasons LDL is elevated in Fredrickson IIa?

Answer 34

LDL no binding to receptor - Familial hypercholesteremia (FH), most common primary dyslipidemia ApoB-100 defective - Familial defective ApoB100 (FDB), 2nd most common. Phenocopy of FH - diagnosis is by detecting of mutation

Question 35

Why does diabetes result in hyperlipidemia?

Answer 35

Metabolism permanently in fasting state so adipose tissue constantly releases FAs and so there are too many FAs in circulation Liver takes up excess FAs and makes TG, assembles VLDL. Diabetic dyslipidemia characterized by high serum TG