Endoplasmic Reticulum: Protein and Lipid Synthesis

Electron Transport Chain

Cytochrome P-450 - NADH cytochrome reductase: This enzyme facilitates the hydroxylation of many substrates. Therefore, it is important in the synthesis of steroid hormones and detoxification processes. Cytochrome b5 - cytochrome b5 reductase NADF4: These endoplasmic reticulum (ER) membrane proteins exhibit asymmetry, with one face oriented towards the hyaloplasm and the other towards the lumen. Carbohydrates are attached to lipids and proteins facing the luminal side.

Synthesis of Exportable Proteins (Rough Endoplasmic Reticulum)

The cell synthesizes proteins that either remain within the cell or are exported to other locations. These locations can be extracellular, as products of secretion, or intracellular. Protein synthesis begins in the hyaloplasm on free ribosomes. The polypeptide chain, as it is being translated from the mRNA, enters a channel within the large ribosomal subunit. This channel aligns with another in the cisternae of the rough endoplasmic reticulum (RER), allowing the newly synthesized protein to enter the RER lumen.

The signal hypothesis explains the difference between mRNAs of exportable and non-exportable proteins. In the mRNA of exportable proteins, a series of signal codons immediately follows the start codon (AUG). These codons are translated into an initial peptide sequence that determines whether the protein is exportable. Exportable protein synthesis occurs in the RER.

Synthesis and Metabolism of Lipids (Smooth Endoplasmic Reticulum)

Lipid synthesis and metabolism primarily occur in the smooth endoplasmic reticulum (SER), except for some fatty acids and phospholipids that are synthesized in the mitochondria. The SER is involved in the synthesis of phospholipids, phosphoglycerides, cholesterol and its derivatives, and steroid hormones.

Cholesterol is used in mitochondria to produce an intermediary molecule (pregnenolone). This molecule is exported to the SER membrane, where it undergoes hydroxylation. This process transforms the intermediary into estrogen, androgen, or progesterone. Alternatively, it can be transformed into other metabolites that return to the mitochondria to become cortisol or aldosterone. This process occurs in the adrenal cortex cells.

Other Functions of the Smooth Endoplasmic Reticulum

• The SER participates in the elongation and desaturation of fatty acids.
• In muscle cells, it serves as a calcium store, as its membranes contain Ca-dependent ATPases.
• It plays a role in glycogen metabolism in the liver, where glycogen is stored in the cytoplasm of hepatocytes.
• It plays a crucial role in detoxification.

Glycosylations

Glycosylation involves the addition of sugars to lipids and proteins synthesized in the ER. This process is carried out by glycosyltransferases.

Detoxification

The ER membrane is a site for the metabolism of toxic substances. Toxins are eliminated in the ER membrane of organs such as the liver, skin, lungs, kidneys, and intestines. This metabolism involves two types of reactions:

1. Oxidation: This process inactivates toxic substances using oxygen, cytochrome P-450, and its reductase, which oxidizes the toxic substance.
2. Conjugation: This process is performed with glucuronic acid. The toxic substance is inactivated in the presence of this acid, either directly or after oxidation.

Endoplasmic Reticulum Biogenesis

Proteins are synthesized in newly formed compartments. External peripheral proteins are synthesized in polysomes, while internal peripheral proteins are synthesized in ribosomes. The proteins in the endoplasmic reticulum undergo glycosylation, which is essential for proper folding. If they fail to bind to chaperones (calnexin or calreticulin), they are exported to the hyaloplasm and degraded.