Smooth endoplasmic reticulum

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3D representation of smooth endoplasmic reticulous (smooth endoplasmic) in blue, which poses continuity with the roaring endoplasmic reticle.

The smooth endoplasmic reticulum (ERL) is a cellular organelle consisting of a network of interconnected membrane tubules that continue with the cisterns of the endoplasmic reticulum.
Unlike the rough endoplasmic reticulum, it does not have ribosomes associated with its membranes (hence the name smooth) and, consequently, most of the proteins it contains are synthesized in the rough endoplasmic reticulum. It is abundant in those cells involved in lipid metabolism, detoxification and calcium storage.

It participates in cell transport, in the synthesis of lipids —triglycerides, phospholipids for the plasmatic membrane, steroids, in purification —thanks to enzymes that metabolize alcohol and other chemical substances— in glycogenolysis —an essential process to maintain the adequate blood glucose levels—, and acts as a calcium reservoir.

Structure

The ultra-structure of the smooth endoplasmic reticulum shows that it is formed by a lipid bilayer membrane. In reality, smooth endoplasmic reticulums have different functional variants that only have in common their appearance and the absence of ribosomes.

Function

The smooth endoplasmic reticulum is involved in a series of important cellular processes, of which, in order of importance, we can highlight: The clearance of penetrating substances (such as liver function), the synthesis of lipids, the dephosphorylation of glucose-6-phosphate, and acting as an intracellular reservoir of calcium.

Lipid synthesis

The membranes of the smooth endoplasmic reticulum produce most of the lipids required for the elaboration of the new cell membranes, including glycerophospholipids and cholesterol. Much of the synthesis of sphingolipids takes place in the Golgi apparatus, but their basic structure, ceramide, is also synthesized in the reticulum. Actually, in the membranes of the reticulum not all the steps of the synthesis of the lipids of the membranes are carried out. Fatty acids are synthesized in the cytosol and are subsequently inserted into the membranes of the smooth endoplasmic reticulum where they are transformed into glycerophospholipids.

This synthesis is carried out by membrane proteins that have their active centers oriented towards the cytosol and, therefore, the lipids will initially be in the cytosolic hemilayer of the membrane. As the passive switching of lipids between hemilayers, or flip-flop movement, it is difficult due to the hydrophobic environment of the fatty acid chains of the membrane, for some of them to reach the inner hemilayer from the external one requires the existence of lipid transporters.

There are several types of lipid transporters between the two hemilayers of the membrane that are distributed throughout the different membranous compartments, including the plasma membrane. Some are specialized in transporting from the cytosolic hemilayer to the extracellular (the internal space of the organelles can be considered as extracellular), while others do it in the opposite direction. These are called flippases and floppases, respectively, and they consume energy. There are others called "mixers" (scramblases in English) that transport lipids in both directions. Consequently, the asymmetry is established along the vesicular pathway and the characteristics of this asymmetry depend on the carrier proteins they possess. The sugars that will form the glycolipids and that assemble inside the reticulum and the Golgi apparatus, and will not be exposed to the cytosol, also contribute to the asymmetry. Therefore, the asymmetric localization of lipids in the membranes does not depend on the initial synthesis in the endoplasmic reticulum.

Cholesterol is another important component of membranes, especially plasma, which is mainly synthesized in the smooth endoplasmic reticulum. From here it is transported via the vesicular pathway or by soluble protein carriers. For example, yeasts, which have ergosterol in their membranes instead of cholesterol, use nonvesicular pathways to transport ergosterol from the reticulum to the plasma membrane. These transporters are diverse and their movements are independent of ATP.

Mitochondria and peroxisomes are not part of the vesicular pathway, so their membrane lipids must be imported. To do this, they use lipid transporters. For example, for glycerophospholipids there are soluble proteins called glycerophospholipid exchangers that have the ability to transport them through the cytosol. They take them up in the smooth endoplasmic reticulum membrane and release them into those of these organelles. In the cells of the photosynthetic tissues, the chloroplasts are in charge of synthesizing their own glycerophospholipids and glycolipids.

In the smooth endoplasmic reticulum lipids such as triacylglycerols are also synthesized and stored in the reticulum itself. This process is very active in adipocytes, cells that store fat, with two functions: food reserve and thermal insulation. It is also primarily responsible for the synthesis of the lipid part of lipoproteins, for the production of steroid hormones and bile acids.

Cleansing and glycogenolysis

Depuration consists of the transformation of metabolites and drugs such as barbiturates or ethanol into water-soluble compounds that can be excreted in the urine. Purification takes place thanks to a series of oxygenase enzymes, including cytochrome P450, which, given its non-specificity, are capable of purifying thousands of hydrophobic compounds, transforming them into hydrophilic ones, which are easier to excrete; carry out hydroxylation reactions (attachment of hydroxyl groups to an organic molecule), which increases the solubility of foreign compounds and facilitates their transport out of the cell and the body of the organism.

In addition, the REL is involved in the process of glycogenolysis, the breakdown of glycogen to release glucose. Glycogenolysis takes place in the cytosol, where glycogen granules are closely related to the ERL. Glucose 6-phosphate (glucose 6-P), the breakdown product of glycogen, cannot cross the cell plasma membrane; for this, it is converted by glucose-6-phosphatase (an enzyme located in the membranes of the smooth endoplasmic reticulum) that catalyzes the hydrolysis of the phosphate group, thus allowing glucose to cross the cell membrane into the bloodstream. It is an essential process to maintain adequate blood glucose levels.

Depuration: It is a process that is carried out mainly in the liver cells and that consists of the inactivation of toxic products such as drugs, medicines or the products of cellular metabolism, because they are fat-soluble (hepatocytes).

Glycosylation: These are transfer reactions of an oligosaccharide to the synthesized proteins. It takes place in the membrane of the endoplasmic reticulum. In this way, the synthesized protein is transformed into an external peripheral protein of the glycocalyx.

Glucose mobilization: When the body needs glucose between meals or during muscular exercise, the hepatic reserves of this monosaccharide stored as glycogen inclusions are mobilized into the blood:::

Dephosphorylation of glucose-6-phosphate

Glucose is usually stored as glycogen, mainly in the liver. This organ is the main one in charge of providing glucose to the blood, thanks to the regulation carried out by the hormones glucagon and insulin. Glycogen breakdown produces glucose-6-phosphate which cannot cross membranes and therefore cannot leave cells. Glucose-6-phosphatase is responsible for eliminating this phosphate residue, allowing glucose to be transported to the outside of the cell.

Glucose-6-phosphatase storage: is an integral protein of the endoplasmic reticulum and is absent in other cells that store glycogen. We only find it in the REL of the Liver.

Intracellular reservoir of calcium (Ca2+)

The ERL in muscle cells, where it is called the sarcoplasmic reticulum (SR), adopts a highly specialized conformation that is related to sarcomeres and T-tubules, and act as a reservoir for calcium ions (Ca²⁺). If a motor neuron receives a nerve impulse, it triggers the release of acetylcholine at the neuromuscular junction. The binding of acetylcholine to its receptors in the muscle cell leads to depolarization of the membrane and the consequent release of calcium ions stored in the sarcoplasmic reticulum into the cytosol. These cytosolic Ca²⁺ ions trigger muscle contraction. When the action potential ends, calcium ions stop being released and are actively transported to the SR (transport mediated by the action of a calcium pump located in the SR membrane), producing muscle relaxation.

Calcium storage and release: Calcium is needed in skeletal muscle to produce muscle contraction. In this type of cells it is called the Sarcoplasmic Reticulum (RS).