Advanced Nutrition Macros :Lipoproteins

Apo lipoprotein B48

important for secretion of chylomicrons from intestines

Why does deficiency in Apo CII lead to hypertriglyceridemia?

-Apo CII activates Lipoprotein Lipase (LPL) so a deficiency in Apo CII means LPL cannot hydrolyze or break down chylomicron TG, resulting in an increase of TG.

-Apo CII present in CM (made in intestine) and VLDL (made in liver)

chylomicron vs chylomicron remnant

• CM is secreted by the intestine. CM will have dietary TG within in them, since TG are taken up by Lipoprotein Lipase (LPL), it loses half of its TG, loses Apo A, and Apo C. You are left with small lipoprotein called the remnant which is taken up by the liver.

• chylomicron remnants have less TG chylomicrons

Low density lipoproteins (LDL)

-responsible for delivering cholesterol to cells.

• LDL comes from VLDL.

• LDL - major supply of cholesterol in cells

Apo CII

activates Lipoprotein Lipase (LPL) - speeds VLDL clearance

Apo CIII

inhibits lipoprotein lipase (LPL) - slows VLDL clearance

Angiopoietin-like 4 (ANGPTL4)

inhibits LPL - slows VLDL clearance

aka Fiaf - fasting induced adipocyte factor

Apo E

• necessary for uptake of chylomicron remnants by the liver (via remnant receptor)

• has 3 alleles (E2,E3,E4)

atherosclerosis

E2/E2 (Arg 158 --> Cys) have elevated blood lipids (TG cholesterol)

-cause: poor binding of E2 to the hepatic remnant receptor

associated with Alzheimer's Disease and atherosclerosis

E4/E4 (Cys 112 --> Arg)

where is LPL found?

in adipose tissue muscle tissue (not in liver)

most people have ApoE3 allele

60% E3/E3; 35% heterozygous E3

Apo B100

• part of VLDL (made in the liver)

• needed for VLDL remnants to be taken up

• without ApoB100 then remnants don't get taken up by the liver

major sources of liver cholesterol

• dietary cholesterol --> chylomicron remnants

• de novo synthesis in the liver

• CH synthesized in extra hepatic tissues --> HDL

major routes in which cholesterol leaves

• secretion of HDL and VLDL

• free cholesterol secreted in bile

• conversion to bile acids/ salts

rate determining enzymatic step for de novo cholesterol biosynthesis

ACC acetyl coa carboxylase

activated by insulin (dephosphorylation)

inactivated by glucagon (phosphorylation)

How do statins lower blood cholesterol levels?

they work by reducing the liver's production of cholesterol. they block an enzyme called HMG CoA Reductase that the liver uses to make cholesterol, so blocking it blocks CH synthesis

How do PCSK9 inhibitors lower blood cholesterol levels?

degrades enzyme that degrades LDL receptors outside of cell, so PCSK9 inhibitors decreases LDL receptor degradation, leading to lower levels of LDL in the bloodstream