Familial Hypercholesterolemia and Atherosclerosis

A genetic disorder causing high LDL cholesterol levels.

Many FH cases involve a faulty LDL receptor, impacting cholesterol removal.

FH often passes from parent to child with one faulty gene.

Having one normal and one mutated gene for FH.

Having two mutated genes for FH; more severe.

LDL levels above 190 mg/dL (adults), 160 mg/dL (children).

Hardening & narrowing of arteries by plaque buildup.

Most common FH symptom; chest pain during exertion.

Chest pain or discomfort, shortness of breath, dizziness, palpitations, fatigue, nausea, stomach issues, and weakness.

Dyslipidemia, diabetes, smoking, family history, sedentary lifestyle, obesity, and hypertension are key risks.

The main enzyme in cholesterol production and the target of statin drugs.

Drugs that reduce cholesterol production by inhibiting HMG CoA.

Cholesterol derivatives that accumulate when cholesterol levels are high, can inhibit LDL receptors.

Active when energy levels are low reducing cholesterol production.

A network of organelles responsible for breaking down cellular waste, including proteins and other cellular debris.

A process where cells take in materials from outside, using vesicles to transport them to lysosomes for degradation.

A process where cells digest their own damaged or unnecessary components, using autophagosomes to transport them to lysosomes.

A vesicle in the endocytic pathway that receives materials taken in from outside the cell.

A mature endosome in the endocytic pathway that is acidic and prepares to fuse with lysosomes.

A vesicle in the autophagic pathway that encapsulates cellular debris for transport to lysosomes.

A hybrid organelle formed by the fusion of an autophagosome with a lysosome, where degradation of cellular debris occurs.

A protein pump that acidifies lysosomes, enabling the action of digestive enzymes.

A region on HMG CoA reductase that detects cholesterol levels and regulates its own activity.

Membrane-bound organelles that act as the recycling center of the cell.

Enzymes inside lysosomes that break down complex molecules into simpler ones.

Hydrolytic enzymes that work optimally in acidic environments.

A controlled process of cell self-destruction.

A family of lysosomal proteases (protein-degrading enzymes) involved in cellular breakdown.

Lysosomes serve as the recycling center, breaking down old cell parts and invading pathogens. They also initiate programmed cell death when necessary.

Enzymes within lysosomes that break down various molecules, working best in acidic conditions.

The pH inside lysosomes can change as they fuse with other compartments or take in substrates, affecting enzyme activity.

Lysosomes are found within the cytoplasm of eukaryotic cells, with the exception of red blood cells.

Lysosomes are typically spherical and range from 50-70 nanometers in diameter.

Lysosomes are too small to be seen with a regular light microscope. You need an electron microscope or a fluorescence microscope to observe them.

TFEB, a special protein, plays a key role in creating more lysosomes within cells. It's like a construction supervisor for lysosomes.

TFEB activates genes that produce: lysosomal enzymes (for breaking things down), lysosomal membrane proteins (for connecting lysosomes to other cell parts), and v-ATPase (for making the lysosome acidic).

This network contains specific DNA sequences (the 'CLEAR element') that TFEB recognizes and binds to, causing more lysosomes to be made.

TFEB works by directly attaching to the CLEAR motif in target genes, making those genes more active.

Autophagy is like house cleaning. The cell gets rid of damaged parts, using autophagosomes to clean them up. This process helps recycle useful parts for the cell, kind of like recycling.

TFEB can also activate the lysosomal pathway by increasing production of LAMP1, a protein that helps create lysosomes.

The V-ATPase complex helps to keep the lysosome acidic, which is essential for it to break down things.