Chapter 18 - Metabolism and Movement of Lipids

18.1: Phospholipids and Sphingolipids: Synthesis and Intracellular Movement

Fatty acids are composed of:
- Phospholipids
- Sphingolipids
- Triglycerides
The synthesizing of fatty acids occurs through water-soluble enzymes which are modified through the endoplasmic reticulum
The synthesizing final steps are catalyzed by membrane associations in the ER, Golgi, mitochondria, and peroxisomes
Pre-existing membranes have each type of membrane initially incorporated into it
The exoplasmic and cytosolic leaflets distribute membrane phospholipids

The cytosol is the main base for the initial steps in cholesterol biosynthesis, and the last steps take place in the ER membrane
HMG-CoA reductase catalyzes the rate-controlling step required for cholesterol biosynthesis
HMG-CoA has transmembrane segments embedded into the ER
The biosynthetic precursors of steroid hormones are intermediated by cholesterol and isoprenoid, and lipid-soluble vitamins, bioactive molecules, and bile acids also helped
There is evidence that indicates that cholesterol and phospholipid membrane movement is not highly dependent on the Golgi complex
Systems that help with cholesterol and phospholipid transport:
- Golgi independent vesicular transport
- Direct protein-mediated contacts that travel between different membranes
- Soluble protein carriers
StAR proteins move cholesterol through the mitochondria for the function of steroid hormone synthesis
StAR proteins have a hydrophobic cholesterol building pocket
NPC1 is needed for cholesterol to move normally into intracellular compartments

Proteins needed for lipid movement in and out of cells
Cell surface transport proteins and water-soluble binding proteins; or
Lipoprotein secretion and lipoprotein receptor facilitated uptake
Fatty acids are transported in the plasma membrane through fatty acid transporters such as FATPs and CD36, and these fatty acids are moved between intracellular binding proteins and extracellular carriers
The ABC superfamily, which is made of ATP hydrolyzing small molecule pumps, controls ABC proteins which control the export of lipids in the cells
Lipids in lipoprotein cores:
- Cholesterol
- Esters
- Triglycerides
Lipoproteins all have a unique characteristic protein and a different function in the cellular export system

Enzymes, transporters, receptors, and proteins are controlled by two key transcription control pathways
The active nSREBP transcription factor is released from the Golgi in the insig-1(2)/SCAP/SREBP pathway by intramembrane proteolysis, which occurs when the cholesterol levels are low
It then acts like a gene expression containing sterol regulatory elements (SREs)
Membrane proteins in the lipid metabolism can have homologous transmembrane sterol sensing domains in them
Domains like this can help with detection and responses to changes in levels of both lipids and sterols

Atherosclerosis progressively accumulates cholesterol, the extracellular matrix, and inflammatory and other cells
If the atherosclerotic plaques cause partial or complete blockage of the coronary arteries then the heart cannot get its needed nutrients, which can ultimately cause a heart attack (similarly, this happening to the brain causes a stroke)
Infection or injury can cause inflammatory responses in the artery wall, which cause foam cells that show atherosclerosis
Plasma LDL (bad cholesterol) causes the formation of foam cells
Plasma HDL (good cholesterol) reverses the transport of cholesterol, lessening the risk of atherosclerosis
Two drugs used to treat atherosclerosis:
- Statins (reduces cholesterol biosynthesis)
- Bile acid sequestrants (prevent enterohepatic recycling of bile acids)