Membrane-bound organelles (Endomembrane System))

endomembrane system

is a group of membranes and organelles in eukaryotic cells that works together to modify, package, and transport lipids and proteins between organelles (trafficking).

• includes the endoplasmic reticulum, the Golgi apparatus, endosomes, and lysosomes (but not peroxisomes)

Endoplasmic Reticulum

• A continuous network of flattened sacs, tubules, and associated vesicles that stretches throughout the cytoplasm of the eukaryotic cell

ROUGH ENDOPLASMIC RETICULUM

• synthesizes and secretes proteins in the liver, hormones, and other substances in the glands. ➢ prominent in cells where biosynthesis, protein synthesis, and protein processing happen ➢ the density is higher near the nucleus and the Golgi apparatus

• plays a vital role in protein folding

translation.

• Ribosomes on the rough endoplasmic reticulum are called ‘membrane-bound’ and are responsible for the assembly of many proteins. This process is called ____

• assembly of parts to make a protein.

Transcription

• process of getting instructions to make protein.

SMOOTH ENDOPLASMIC RETICULUM

• does not have ribosomes and is in tubular form. ➢ It participates in the production of phospholipids and cholesterol, the chief lipids in cell membranes, and is essential in the process of metabolism. (CHO)

• transports the products of the rough ER to other cellular organelles, especially the Golgi apparatus

• responsible for the production and secretion of steroid hormones

• stores and releases calcium ions. These are quite important for the nervous system and muscular systems.

OTHER FUNCTIONS of SMOOTH ENDOPLASMIC RETICULUM

• primarily involved in processing or storing non-protein molecules within the cells.

Drug detoxification

• The enzymes of the smooth endoplasmic reticulum help detoxify drugs and poisons, especially in liver cells

Hydroxylation

• Detoxification by smooth ER usually involves adding a hydroxyl group  ———- to drug molecules, thus making them more soluble and easier to flush from our bodies

ex. The cytochrome p450 enzymes find unusual molecules and add oxygen atoms to them. In most cases, this has the effect of making the molecule more soluble in water, and thus, easier to flush out of the body

Carbohydrates metabolism

• It is involved in the enzymatic breakdown of stored glycogen. Glycogen phosphorylase breaks down glycogen into glucose 1- phosphate, whereas glycogen synthase synthesizes glucose 1-phosphate molecules into glycogen. Glucose 1-phosphate can be interconverted into glucose 6-phosphate by phosphoglucomutase.

Glycogenolysis

is the breakdown of glycogen in the liver when blood glucose levels drop. It occurs in the liver, muscles, and adipose tissue.

Gluconeogenesis

is the synthesis of glucose from noncarbohydrate sources like lactic acid, glycerol, and amino acids. It occurs in the liver and kidneys.

Glycogenesis

is the process of storing excess glucose for use by the body at a later time.

Glycolysis

breaks down a glucose molecule into pyruvate, ATP, and NADH.synthesis

Calcium Storage

The sarcoplasmic reticulum present in the muscle cells is an SER that specializes in the storage of calcium. The ER lumen contains high concentrations of calcium-binding proteins.

Calcium ions are pumped into the ER by ATPdependent calcium ATPases and released in response to extracellular signals to aid in muscle contraction.

Sarcoplasmic reticulum

storage of calcium ions to be released when stimulated by an impulse

T-tubules

surrounds the myofibrils and assist in delievering ions

Steroid Biosynthesis

The SER is the site of biosynthesis of cholesterol and steroid hormones such as cortisol, testosterone, and estrogen.

1. cortisol-producing cells of the adrenal gland.

2. the Leydig cells of the testes (produce testosterone)

3. the cholesterol-producing cells of the liver

4. the follicular cells of the ovary (produce estrogen)

Large amounts of smooth ER:

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase

inhibitors, also known as "statins," are used adjunctively to diet and exercise to treat hypercholesterolemia by lowering total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and triglycerides (TG) concentrations while increasing high-density lipoprotein (HDL)

Golgi apparatus, or Golgi complex

functions as a factory in which proteins received from the ER are further processed and sorted for transport to their eventual destinations: lysosomes, the plasma membrane, or secretion. In addition, glycolipids and sphingomyelin are synthesized

The functions of Golgi apparatus

• synthesis of polysaccharides,

• modification of products of the rough and smooth ER,

• production of lysosomes, and

• the sorting and transport of modified products in the transport vesicles.

Distinct Sides/Faces of Golgi Stack

During their passage through the Golgi apparatus, transported molecules undergo an ordered series of covalent modifications.

➢ a cis face (or entry face)

➢ a trans face (or exit face)

trans-Golgi network (TGN)

is a major secretory pathway sorting station that directs newly synthesized proteins to different subcellular destinations. The TGN also receives extracellular materials and recycled molecules from endocytic compartments

cis-Golgi network (CGN)

is a large tubulovesicular network that connects to the cis face of the Golgi stack and receives and processes biosynthetic output from the ER

Medial cisternae

mature into trans cisternae. Both medial and trans cisternae are involved in carbohydrate synthesis, with early-acting enzymes concentrated in medial cisternae and late-acting enzymes in trans cisternae.

CGN, TGN, Medial Cisternae

the Golgi apparatus are biochemically and functionally distinct. Each compartment contains specific receptor proteins and enzymes necessary for specific steps in protein and membrane processing.

Stationary cisternae model,

each compartment of the Golgi stack is a stable structure. Trafficking between successive cisternae is mediated by shuttle vesicles that bud from one cisterna and fuse with the next cisterna in the cis-to-trans sequence. Proteins destined for the TGN are simply carried forward by shuttle vesicles, whereas molecules that belong in the ER and successive Golgi compartments are actively retained or retrieved.

Cisternal maturation model

Golgi cisternae are transient compartments that gradually change from CGN cisternae through medial cisternae to TGN cisternae. In this model, transition vesicles from the ER converge to form the CGN, which accumulates specific enzymes for the early steps of protein processing.

Anterograde transport

refers to the pathway that newly synthesized proteins take from the endoplasmic reticulum (ER) through the Golgi complex to the plasma membrane.

Retrograde transport

refers to transport in the reverse direction—the flow of vesicles from the Golgi cisternae back towards the ER.

glycosylation, glycoproteins

The protein processing within the ER and Golgi includes protein folding, quality control, and _____– adding CHO side chains to specific amino acid residues of proteins, forming __

O-linked glycosylation

involves the addition of an oligosaccharide to the oxygen atom on the hydroxyl group of certain serine, threonine, and in some cases tyrosine residues.

N-linked glycosylation

involves the addition of a specific oligosaccharide unit to the nitrogen atom on the terminal amino group of certain asparagine residues.

Unfolded Protein Response (UPR)

uses sensor molecules in the ER membrane to detect misfolded proteins. (PERK, IREI and ATF6)

➢ It is an adaptive reaction that reduces unfolded protein load to maintain cell viability and function.

➢ A homeostatic signaling network that orchestrates the recovery of ER function, and failure to adapt to ER stress results in apoptosis.

ER –Associated Degradation (ERAD)

➢ recognizes misfolded and unassembled proteins and export or retro-translocates them back across the ER membrane to cytosol.

➢ ensures that only properly folded and assembled proteins are transported to their final destinations. Besides its role in protein folding and transport in the secretory pathway, the ER regulates the biosynthesis of cholesterol and other membrane lipids.

Protein Trafficking

how nuclear protein reach their final destination

Categories of Trafficking

➢ The endomembrane system

➢ The cytosol

➢ Mitochondria, chloroplast, peroxisomes, and other related organelles

posttranslational import.

polypeptides destined either for cytosol (remain in the cytosol as their final destination and taken by appropriate organelles which happen in the presence of special targeting signals called ____

cotranslational import.

those polypeptides destined in the endomembrane system or for export from the cell. The ribosomes are attached to the ER during the translation process and as they grow they are transferred across the ER membrane. The transfer of polypeptides into the ER is called ____

Endocytosis and exocytosis

are the processes by which cells move materials into or out of the cell that are too large to directly pass through the lipid bilayer of the cell membrane. Large molecules, microorganisms and waste products are some of the substances moved through the cell membrane

Exocytosis

is the process by which cells move materials from within the cell into the extracellular fluid. ___ occurs when a vesicle fuses with the plasma membrane, allowing its contents to be released outside the cell.

Exocytosis function

➢ Removing toxins or waste products from the cell’s interior

➢ Facilitating cellular communication

➢ Facilitating cellular membrane growth, repair, signaling, and migration

Constitutive exocytosis

Exocytosis which requires no signal is required for releasing the secretory materials outside the cell

Regulated exocytosis

The exocytosis that requires an external signal for releasing secretory materials outside the cell

Endocytosis serves many purposes:

➢ Taking in nutrients for cellular growth, function, and repair

➢ Capturing pathogens or other unknown substances that may endanger the organism:

➢ Disposing of old or damaged cells

Phagocytosis

, also known as cell eating, is the process by which cells internalize large particles or cells, like damaged cells and bacteria.

Pinocytosis

also known as cell drinking

Receptor-mediated endocytosis

known as clathrin-dependent endocytosis is a specialized type of pinocytosis. During ______ endocytosis, macromolecules bind to receptors along the surface of the cell’s plasma membrane. Cholesterol uptake

Coated vesicles

involved in vesicular traffic throughout the endomembrane system, as well as transport during exocytosis and endocytosis. It is probable that such vesicles participate in most if not all, vesicular traffic connecting the various membrane-bounded compartments and the plasma membrane of the eukaryotic cell

lysosome

• is an organelle of the endomembrane system that contains digestive enzymes capable of degrading all the major classes of biological macromolecules – lipids, CHO, nucleic acids, and proteins

• organelle that contains digestive enzymes and acts as the organelle-recycling facility of an animal cell. It breaks down old and unnecessary structures so their molecules can be reused

Hunter syndrome (MPS II)

is distinguished from Hurler syndrome by an X-linked recessive inheritance, longer survival, lack of corneal clouding, and the different biochemical defect with deficiency of the lysosomal enzyme iduronate-2-sulfatase.

Tay-Sachs disease

s categorized as a lysosomal storage disease. Lysosomes are the major digestive units in cells. Enzymes hexosaminidase within lysosomes break down or “digest” nutrients, including certain complex carbohydrates and fats