Chapter 12: The Endomembrane System

Endomembrane System: A complex of membranes and organelles inside a eukaryotic cell responsible for the synthesis, modification, packaging, and transport of various molecules.
- Structures involved include:
  - Nuclear envelope
  - Endoplasmic reticulum (ER)
  - Ribosomes
  - Golgi apparatus
  - Secretory vesicles
  - Lysosomes
  - Plasma membrane

Functions in making, modifying, packaging, and transporting proteins and lipids within the cell.
Pathway of transport:
- Nucleus → ER → Golgi → vesicles → cell membrane (or lysosomes/vacuoles)

Description:
- Continuation of the nuclear membrane.
- Studded with ribosomes, serving as the site of protein synthesis.
Protein Processing:
- Proteins enter the ER lumen where they undergo modifications, such as glycosylation.
- Proteins are packaged into transport vesicles that bud off and are sent to the Golgi apparatus.
Ribosome Functionality:
- Proteins destined for the ER begin their synthesis on free-floating cytoplasmic ribosomes.
- Ribosomes later attach to receptors on the ER.
- This process includes:
  - Translocon: A receptor complex that allows the protein to be released into the lumen or embedded in the membrane.
  - Process of protein entry: Cotranslational translocation.

Functionality:
- Synthesizes lipids, including phospholipids and steroids.
- Detoxifies drugs and various substances, especially in liver cells.
- Stores calcium ions, particularly in muscle cells, and transports materials to the Golgi via vesicles.
Hydroxylation Reaction:
- Involves adding a hydroxyl group (-OH) to a molecule.
- Cytochrome P450: Enzyme in Smooth ER responsible for hydroxylation; it modifies proteins and facilitates detoxification of drugs.

Description:
- Organelle that modifies, sorts, and transports proteins and lipids made in the ER.
- Composed of flattened, stacked membrane "sacs" called cisternae.
Cisternae Functionality:
- Cis face: Receives items from the ER.
- Trans face: Sends processed molecules to their final destinations.
Transport Vesicles:
- Spherical lipid bilayer structures that bud off from one organelle and fuse with another, functioning in transporting items.

Anterograde Transport: Movement of molecules through the secretory pathway from the ER to the Golgi to the plasma membrane or lysosome.
Retrograde Transport: Involves movement of materials backwards, usually from the Golgi back to the ER.
- Purpose includes:
  - Returning misfolded or escaped ER proteins.
  - Recycling Golgi enzymes.
Endocytosis: Process where the plasma membrane engulfs external substances, forming a vesicle.
- Not to be confused with phagocytosis and pinocytosis:
  - Phagocytosis: Engulgement of large, solid particles.
  - Pinocytosis: Engulgement of fluid/dissolved solutes.

Definition: Specialized endocytosis whereby cells selectively intake molecules using cell-surface receptors.
Steps:
1. A ligand binds specifically to a receptor on the cell surface.
2. Receptor-ligand complexes gather in clathrin-coated pits.
3. The pit pinches inward, forming a clathrin-coated vesicle that enters the cell.
Clathrin: A structural protein that forms a triskelion shape, which assembles into a lattice, forcing the membrane to bend inward.
Dynamin: An enzyme critical for pinching off vesicles during RME, forming a spiral collar to sever the vesicle from the plasma membrane.

After vesicle formation, it sheds its clathrin coat and fuses with an early endosome or lysosome for processing.

Endosome: Membrane-bound vesicle inside the cell that sorts material brought in by endocytosis.
Involves separating ligands from their receptors for recycling or sending contents to lysosomes.

Functionality:
- Break down macromolecules.
- Recycle damaged organelles.
- Digest foreign materials, such as bacteria and debris.
- Contain digestive enzymes to facilitate these processes.

Definition: The process by which vesicles fuse with the plasma membrane to release their contents (e.g., hormones, neurotransmitters, enzymes) outside the cell.

Definition: Post-translational modification where sugar molecules (glycans) are enzymatically attached to proteins or lipids, altering their structure, stability, and function.
N-linked Glycosylation:
- Sugar attachment to the nitrogen of an asparagine side chain in a protein.
- Occurs in the ER and Golgi.
- Functions to assist in protein folding, stabilize protein structure, and protect from degradation.
O-linked Glycosylation:
- Sugar attachment to the oxygen of serine or threonine side chains in proteins.
- Functions to fine-tune protein function, support membrane stability, and modify signaling proteins.
- Primarily occurs in the Golgi apparatus.

Examples:
- Type II Glycogenosis (Pompe Disease): Caused by deficiency of acid alpha-glucosidase, leading to glycogen buildup and cell damage, especially in muscle cells.
- Hurler and Hunter Syndromes: Inabilities to break down glycosaminoglycans (GAGs) due to lack of enzymes, resulting in skeletal deformities and developmental delays.

Contain catalase, which utilizes hydrogen peroxide to detoxify harmful substances and break down fatty acids.
Origin and Formation: Can arise from binary fission of existing peroxisomes or through the creation of vesicles from the smooth ER that contain peroxisomal membrane proteins. Peroxisomes import their own enzymes from free ribosomes in the cytosol after formation.
Functions: Involved in various metabolic processes and transport mechanisms, crucial for the endomembrane system functionality.