Cholesterol Metabolism and Regulation

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Questions and Answers

What type of proteins does the endosome–lysosome pathway primarily degrade?

Proteins from the nucleus

Intracellular organelles

Membrane-bound receptors only

Extracellular and cell-surface proteins (correct)

What role does HDL play in cholesterol transport?

HDL delivers dietary triglycerides to adipocytes.

HDL unloads triglycerides and remaining cholesterol directly into cells.

HDL transfers cholesterol from peripheral cells back to the liver. (correct)

HDL is involved in the degradation of misfolded proteins.

Which proteolytic pathway is specifically associated with degrading proteins from the cytoplasm, nucleus, and endoplasmic reticulum?

Autophagic pathway

Ubiquitin–proteasome pathway (correct)

Mitochondrial pathway

Endosome–lysosome pathway

How do chylomicrons function in cholesterol transport?

They deliver dietary triglycerides to adipocytes. Signup and view all the answers

How does the proteasome carry out protein degradation?

By a highly targeted mechanism using ubiquitin Signup and view all the answers

What initiates the ERAD pathway?

Identification of misfolded or aberrant proteins by quality control receptors. Signup and view all the answers

What is a key feature of the mitochondrion's proteolytic system?

It is similar to proteolytic systems in prokaryotes Signup and view all the answers

What happens to misfolded proteins during the ERAD process?

They undergo retrotranslocation and ubiquitination for degradation. Signup and view all the answers

Which enzyme is responsible for transferring ubiquitin from E1 to E2 in the ubiquitin-proteasome system?

Ubiquitin-activating enzyme E1 Signup and view all the answers

What is the primary function of LDL in cholesterol transport?

LDL transfers cholesterol from the liver to peripheral cells. Signup and view all the answers

What does the proteasome primarily degrade?

Individual cellular proteins Signup and view all the answers

What does feedback inhibition by cholesterol involve?

Cholesterol regulating the synthesis of its own production. Signup and view all the answers

What is the characteristic composition of the 26S proteasome?

A 20S barrel and two 19S lids Signup and view all the answers

Which of the following statements correctly describes the cooperation between the endosome–lysosome and ubiquitin–proteasome pathways?

Recent evidence suggests they cooperate. Signup and view all the answers

What is the significance of Scavenger Receptor-B1 in cholesterol transport?

It helps HDL acquire cholesterol from peripheral cells. Signup and view all the answers

What mechanism is paired with the transfer of misfolded proteins during ERAD?

Ubiquitination by an E3 ubiquitin ligase. Signup and view all the answers

What is the primary function of autophagy in cells?

To remove unnecessary or dysfunctional components Signup and view all the answers

Which type of autophagy involves the formation of an autophagosome?

Macroautophagy Signup and view all the answers

What role does the protein hsc70 play in chaperone-mediated autophagy?

It recognizes and binds to specific protein substrates Signup and view all the answers

What occurs after the outer membrane of an autophagosome fuses with a lysosome?

The contents are lysed and degraded Signup and view all the answers

Which of the following is NOT a type of autophagy?

Cellular autophagy Signup and view all the answers

Which factor has been linked to defects in autophagy?

Neurodegeneration and cancer Signup and view all the answers

In which type of autophagy are lysosomal membranes directly invaginated?

Microautophagy Signup and view all the answers

What has become increasingly clear about the role of autophagy in non-starved cells?

It contributes to cellular homeostasis. Signup and view all the answers

What could lead to the accumulation of autophagic vacuoles in aging cells?

Inability of lysosomes to fuse with autophagic vacuoles Signup and view all the answers

How does the insulin receptor affect macroautophagy in aging cells?

It maintains negative signaling that represses autophagy. Signup and view all the answers

What effect does an age-dependent decline in macroautophagy have on cells?

Leads to energetic compromise Signup and view all the answers

What was observed in mice that followed a Fasting Mimicking Diet (FMD)?

Enhanced regeneration in multiple systems Signup and view all the answers

What role does glucagon play in the process of macroautophagy?

It enhances macroautophagy but is less effective in old cells. Signup and view all the answers

Which consequence is most likely a result of inadequate turnover of organelles in aging cells?

Increase in free radical levels Signup and view all the answers

What was a significant finding related to calorie restriction in mice?

It improved learning and memory. Signup and view all the answers

What is a potential consequence of the failure of macroautophagy in older organisms?

Compromised metabolic health Signup and view all the answers

What maintains the low lysosomal pH of 4-5?

V-ATPase pumping H+ into the lumen Signup and view all the answers

What is the primary function of the acid hydrolases present in lysosomes?

Hydrolyze macromolecules to generate building blocks Signup and view all the answers

Which transporter activates mTOR in response to luminal arginine?

SLC38A9 Signup and view all the answers

What role does mTORC1 play in cellular processes?

Regulates the balance between anabolism and catabolism Signup and view all the answers

What does the cellular export of cholesterol from lysosomes primarily involve?

NPC1/NPC2 proteins and SCARB2 Signup and view all the answers

Why is solute efflux important in lysosomes?

To prevent osmotic pressure and membrane tension Signup and view all the answers

What distinguishes proton-coupled amino acid transporters from typical amino acid transporters?

They use H+ for transport instead of Na+ Signup and view all the answers

Which of the following is NOT a function of mTOR?

Degrade lysosomal components directly Signup and view all the answers

What is the function of S6K1 in mRNA translation initiation?

It phosphorylates and activates substrates promoting translation. Signup and view all the answers

Which component is a part of the mTOR Complex 1 (mTORC1)?

PRAS40 Signup and view all the answers

How does mTORC1 regulate mRNA translation at the ribosome?

By phosphorylating 4EBP to promote eIF4E release. Signup and view all the answers

Which factor is NOT involved in the regulation of mTORC1 activity?

GTP from RagC Signup and view all the answers

What role does 4EBP play in translation regulation?

It sequesters eIF4E to inhibit translation. Signup and view all the answers

Which amino acid has been noted as a significant regulator in mTORC1 signaling?

Arginine Signup and view all the answers

What mechanism leads to the recruitment of mTORC1 to the lysosome?

SLC38A9 activating RagA to GTP-bound state. Signup and view all the answers

What is a primary role of mTORC1 in ribosome biogenesis?

Coordinating stimuli for ribosome production. Signup and view all the answers

Study Notes

Dietary Cholesterol Movement

Cholesterol from the diet travels to the liver.
HDL (high-density lipoprotein) collects cholesterol from peripheral cells and returns it to the liver.
Cholesterol from cell membranes is loaded into HDL.
VLDL (very-low-density lipoprotein) releases triglycerides and remaining cholesterol to the liver or peripheral cells via LDL receptors.
Chylomicrons deliver dietary triglycerides to adipocytes and remnants are taken to the liver.

Cholesterol Feedback Inhibition

Cholesterol regulates its own production via feedback inhibition.
Feedback inhibition is a regulatory mechanism where the product of a metabolic pathway (in this case, cholesterol) inhibits an enzyme in the pathway, slowing the production of more product.

ERAD Pathway

ERAD (endoplasmic reticulum-associated degradation) is a cellular pathway for degrading misfolded or unassembled proteins in the endoplasmic reticulum (ER).
ERAD targets proteins to the cytosol for proteasomal degradation.
Proteins are recognized as aberrant by quality control receptors in the ER.
These misfolded proteins are then sorted to an ER membrane complex that includes adaptor proteins and an ERAD substrate.
This process often involves ubiquitination during transport across the ER.
Retrotranslocation complexes extract the ERAD substrate and prepare it for proteasomal degradation.

Proteolytic Pathways in Cells

The endosome-lysosome pathway targets extracellular and cell-surface proteins for degradation.
Intracellular organelles also enter this pathway.
The ubiquitin-proteasome pathway (UPS) targets cytoplasmic, nuclear, and ER proteins for degradation.
Mitochondria also have a proteolytic system.
Evidence suggests cooperation between these pathways.

Autophagy

Autophagy is a cellular process of degradation and recycling of cellular components.
Autophagy is regulated and can play a role in cell homeostasis.
Defects in autophagy have links to several human diseases, including neurodegeneration and cancer.
Macroautophagy, microautophagy, and chaperone-mediated autophagy are three common types.

Ubiquitin-Proteasome System (UPS)

The UPS is a cellular pathway for targeted protein degradation.
It involves ubiquitin, an enzyme called E1, E2, and E3 ligase, and finally, the proteasome.

Consequences of Autophagy Failure

Protein aggregates may accumulate
Organelle turnover is impaired
Free radicals may increase
Energetic compromise can result in the aging cells

Metabolic Health and Life Span

Promoting autophagy may improve metabolic health and lifespan.
Researchers have discovered that periodic fasting mimicking diets can extend lifespan in mice.

mTOR Regulates Cell Growth and Metabolism

mTOR plays a crucial role in regulating energy balance by controlling protein, lipid, and nucleotide synthesis, lysosome autophagy, and biogenesis.
mTORC1 and mTORC2 are the two complexes in the mTOR pathway.
mTORC1 and mTORC2 are regulated by a series of mechanisms.

Amino Acid Sensing and the Lysosome

Amino acid sensing (specifically arginine) is a crucial regulator of lysosomal function.
The activation of the Rag proteins (RagA/B/C/D) and SLC38A9 aminoacid transporter, which detects and relays arginine signals from the lysosome to the mTORC1 pathway directly.
mTORC1 is activated.

Ribosome Production and Regulation

mTORC1 positively regulates several steps in ribosome biogenesis, including rRNA transcription, ribosomal protein synthesis, and ribosome components.
Specific mRNAs can be regulated by mTOR.

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Description

This quiz covers the important mechanisms of dietary cholesterol movement, feedback inhibition, and the ERAD pathway. Test your knowledge on how cholesterol is transported, regulated, and degraded in the body. Perfect for students studying biochemistry and cellular biology.