Cholesterol Biosynthesis and Regulation

Comprehensive vocabulary flashcards covering the components, stages of biosynthesis, regulatory mechanisms, and clinical implications of cholesterol as presented in the lecture notes.

Cholesterol

A vital molecule in animals used as a component of cellular membranes and a precursor for steroid hormones and bile acids, synthesized by all cells from acetate.

Acetate

The single precursor that provides all 27 carbon atoms in the structure of cholesterol.

Isoprene units

The essential 5-carbon intermediates in the biosynthetic pathway from acetate to cholesterol.

HMG-CoA (\beta-hydroxy-\beta-methylglutaryl-CoA)

A six-carbon compound formed in the first stage of cholesterol synthesis by the condensation of acetoacetyl-CoA with a third molecule of acetyl-CoA.

HMG-CoA reductase

An integral membrane protein of the smooth ER that catalyzes the committed step of cholesterol biosynthesis: the reduction of HMG-CoA to mevalonate.

Mevalonate

The six-carbon intermediate produced in the first stage of cholesterol biosynthesis, which is then converted into activated isoprene units.

\Delta^3-isopentenyl pyrophosphate

The first of the two activated isoprene units central to cholesterol formation, produced after phosphorylation and decarboxylation of mevalonate.

Dimethylallyl pyrophosphate

An activated isoprene unit formed by the isomerization of \Delta^3-isopentenyl pyrophosphate.

Geranyl pyrophosphate

A 10-carbon intermediate formed by the head-to-tail condensation of one isopentenyl pyrophosphate and one dimethylallyl pyrophosphate unit.

Farnesyl pyrophosphate

A 15-carbon intermediate formed by the head-to-tail condensation of geranyl pyrophosphate with isopentenyl pyrophosphate.

Squalene

A 30-carbon linear intermediate formed by the head-to-head joining of two farnesyl pyrophosphate molecules.

Lanosterol

The first cyclic structure formed from squalene in animal cells, containing the four characteristic rings of the steroid nucleus.

AMPK (AMP-dependent protein kinase)

An enzyme that mediates short-term regulation of HMG-CoA reductase via phosphorylation, inactivating it when energy (ATP) levels are low.

SREBPs (Sterol regulatory element-binding proteins)

A family of transcription factors that control the expression of genes involved in cholesterol and fatty acid synthesis and uptake.

SCAP (SREBP cleavage-activating protein)

A membrane protein that acts as a sterol sensor and complexes with SREBPs to facilitate their transport from the ER to the Golgi when sterol levels are low.

Insig (Insulin-induced gene protein)

An ER membrane protein that anchors the SCAP-SREBP complex when sterol levels are high and triggers ubiquitin-mediated degradation of HMG-CoA reductase.

Atherosclerosis

A condition caused by the pathological accumulation of cholesterol plaques that obstruct blood vessels, often associated with high LDL-cholesterol levels.

Foam cells

Macrophages that have ingested excess oxidized LDL and accumulated cholesteryl esters, contributing to the formation of atherosclerotic plaques.

Familial hypercholesterolemia

A genetic disorder characterized by extremely high blood cholesterol levels and early atherosclerosis due to defective LDL receptors.

Statins

A class of drugs used to treat elevated serum cholesterol by inhibiting the endogenous synthesis of cholesterol.

Reverse cholesterol transport

The process by which HDL (high-density lipoprotein) picks up cholesterol from extrahepatic tissues and foam cells and carries it to the liver.

ABC Transporters

A class of 48 transporters (ATP-binding cassette) in the human genome, about half of which facilitate the transport of lipids across membranes.