Cholesterol Structure and Function

Cholesterol affects membrane fluidity and integrity in animal cells by packing with fatty acids. It's essential for cell shape change and mobility.

Cholesterol is carried in lipoproteins - both free and esterified forms. LDL delivers cholesterol to tissues, HDL removes it.

Cells store excess cholesterol as cholesteryl esters, combining cholesterol with fatty acids.

Cholesterol makes up a significant portion of lipids in nerve cell membranes.

Sterol Response Element Binding Proteins (SREBPs) are activators of cholesterol and fatty acid synthesis in the liver.

A process where cholesterol is removed from tissues by HDL and transported to the liver where it's processed and can be excreted.

Cholesterol is derived from both diet and produced by the body.

Cholesterol in blood plasma carries cholesterol to and from cells to maintain a stable membrane structure, which also maintains fluidity and integrity.

SREBP-2 primarily regulates cholesterol metabolism genes.

SREBP-1c mainly activates genes involved in fatty acid and triglyceride metabolism.

Cholesterol or oxysterols cause SREBP-Scap to remain in the endoplasmic reticulum (ER).

Cholesterol controls the movement of SREBPs from the ER to the Golgi apparatus by regulating the interaction between Insig-1 and Scap.

In the absence of cholesterol, Insig-1 detaches from Scap and is degraded.

The nuclear form of SREBP activates target genes to make proteins.

Two steps of proteolytic cleavage are needed to release the transcription factor domain of SREBP from the membrane.

Sequences in gene promoters that the SREBP transcription factor binds to.

Scap (SREBP cleavage-activating protein), binds to Insig (insulin-induced gene) in the ER, and this interaction prevents SREBP transport to the Golgi.

High cholesterol levels stabilize Insig-1, preventing SREBP incorporation into transport vesicles, which inhibits cholesterol synthesis.

Enzyme that catalyzes the rate-limiting step in cholesterol synthesis, converting HMG-CoA to mevalonate.

A metabolic pathway that produces important molecules like IPP and DMAPP, used to synthesize isoprenoids (a broad class of molecules).

Statins are medications that inhibit HMG-CoA reductase, reducing cholesterol production in the body.

HMG-CoA reductase is activated by insulin and inhibited by glucagon and oxysterols and by low energy levels (AMPK activation).

Oxysterols, cholesterol derivatives, inhibit HMG-CoA reductase and block LDL receptor-mediated endocytosis.

About 10% of cholesterol in egg yolks and 50% in meat/poultry is in esterified form.

Cholesterol esters need to be broken down into free cholesterol and fatty acids by cholesterol esterase to be absorbed.

Cholesterol esterase, produced and released by the pancreas, breaks down cholesterol esters.

Dietary phytosterols can displace cholesterol from micelles, reducing absorption.

Cholesterol absorption comes from dietary and bile sources.

The efficiency of cholesterol absorption significantly impacts overall cholesterol levels in the body.

Unused or unabsorbed cholesterol is eliminated through the feces.

Cholesterol is absorbed by the intestinal cell (enterocyte) via NPC1L1 protein.

HMG CoA reductase has two parts: a hydrophobic (water-fearing) part in the ER membrane and a hydrophilic (water-loving) part in the cytosol that does the work.

Certain lysines on HMG CoA reductase can be flagged for destruction (ubiquitination) depending on the amount of cholesterol or sterols.

A particular sequence (YIYF) on HMG CoA reductase is how proteins (Insigs) know where to bind.

Oxysterols and pathway intermediates can trigger the breaking down of HMGCR, controlling its amount.

Bile salts help digest fats in the gut by breaking them into smaller pieces.

Cholic acid and chenodeoxycholic acid are the main bile acids made by the liver. These are then changed to bile salts by adding glycine or taurine.

Bile salts in the intestine are processed by bacteria to form secondary bile salts, and can return to the liver.

Recycling system where bile salts travel from the liver to the intestine, and then back to the liver for reuse.

A genetic disorder characterized by high LDL cholesterol levels due to defects in the LDL receptor gene. This leads to an inability to efficiently remove LDL from the bloodstream.

A protein on the surface of cells that binds to LDL, allowing it to enter the cell. It's involved in regulating cholesterol levels in the bloodstream.

Changes within the genetic code for the LDL receptor protein that can disrupt its function. These mutations are the primary cause of FH.

A form of FH where only one copy of the LDL receptor gene is mutated. Individuals with this have higher than normal but usually manageable cholesterol levels.

A rare and severe form of FH where both copies of the LDL receptor gene are mutated. Individuals with this have extremely high and often life-threatening cholesterol levels.

The frequency of FH in a population. Heterozygous FH is more common, occurring in about 1 in 220 individuals. Homozygous FH is much rarer, found in about 1 in 300,000.

A key symptom of FH. Adults with FH often have LDL cholesterol levels over 190 mg/dL, while children have levels over 160 mg/dL.

A pattern of inheritance where a single mutated copy of a gene is enough to cause the disease. FH follows this pattern.