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Primary Active Transport (direct)

In primary active transport, energy from ATP is directly used to transport molecules against their concentration gradient. For example, the Na+/K+-ATPase is a membrane spanning protein carrier. Please note the –ase ending, so it is also an enzyme that hydrolyzes (breaks bonds with water) ATP to get its energy. It is also referred to as the ‘Na+/K+ pump’. This is because it acts much like a pump that is bailing out a leaky ship.  It works non-stop to continuously expel 3 Na+ ions out of the cell and at the same time import 2 K+ ions into the cell per cycle. Each cycle of the pump requires 1 ATP molecule. Both Na+ and K+ are being moved against their concentration gradients, therefore we know that ATP must be required because this is active transport. The ATP is hydrolyzed to ADP + Pi + Energy! This is an antiport mechanism, as both molecules are being transported in opposite directions.  The Na+/K+ pump helps to maintain the resting membrane potential (RMP) across the plasma membrane of all living cells. Draw a diagram of the Na+/K+ pump.

2) Secondary active transport (indirect)

In secondary active transport, the ATP is used indirectly to move molecules across membranes. Essentially what this means is the potential energy that is stored in a concentration gradient is used to help move molecules across a membrane. An excellent illustration of how this is done is seen in the Na+/glucose transporter. The relative concentration of Na+ is low on the inside, high on the outside of the cell. When Na+ moves down its concentration gradient (into the cell) this force is harnessed to move glucose against its concentration gradient (also into the cell). While the Na+ goes down its gradient, the glucose can be dragged along with it, up hill, so to speak. The original source of ATP that allows this to occur is the one used in the Na+/K+ pump described above, as it maintains a low Na+ concentration inside the cell. This is a symport mechanism, as both molecules are being transported in the same direction.  Draw a diagram of the Na+/glucose transporter.

3) Vesicular Transport 

Vesicular transport is used to move large macromolecules or large quantities of a molecule across the plasma membrane. Vesicles are like mini lipid bilayer bubbles that bud off from plasma membrane and encapsulate large molecules. This is an active form of transport that directly requires energy in the form of ATP for the maneuvering of the cytoskeleton.

There are two main forms of Vesicular transport

  1. Endocytosis – bringing material into the cell, inward vesicular transport.
  2. Exocytosis – releasing material from the cell, outward vesicular transport.
  3. Endocytosis: There are three general kinds of endocytosis.

1) Pinocytosis (cell drinking): relatively unselective whereby ECF is transported into the cell.

2) Phagocytosis is a process by which cells engulf a particle or another cell into a much larger vesicle, e.g., certain types of WBC (called Macrophages) engulf bacteria this way.

3) Receptor-Mediated Endocytosis: This is a very selective process. Receptors on the external surface of the plasma membrane bind specific ligands. This ligand-receptor complex then creates a clathrin-coated pit, a type of invagination of the membrane. The membrane then pinches this off as cytoplasmic vesicle, thereby ingesting the ligand-receptor complexes. The vesicle membrane and the receptors are recycled to the surface membrane to be used again.

  1. Exocytosis: This is used by many cells to secrete or release large molecules or large amounts of a molecule. Intracellular vesicles fuse with the plasma membrane, then releases its contents into ECF. This process requires energy and Ca2+ and involves other proteins. An excellent example of how this is commonly used in the body is the release of neurotransmitters from neurons into the synaptic cleft. This process is also used to secrete large lipophobic molecules, such as hormones, protein fibers and mucus across cell membranes. Exocytosis is also used to insert proteins, such as receptors, into membrane. Lysosomes can remove waste in this manner and is often regulated from outside of the cell (e.g., hormone-induced hormone release).

 

Transcytosis and Vesicular Transport

Transcytosis means movement across (trans) a cell (cytosis); it can involve endocytosis, then vesicular transport across cell, then exocytosis out of the cell at the other end. So the substance has moved completely across the cell. This provides for movement of large proteins intact, e.g., the absorption of maternal antibodies through breast milk, or the movement of proteins across capillary endothelium.

Continue reading “Primary Active Transport (direct)”

Specificity

Protein carriers move only one type or family of closely related molecules. For example, GLUT transporters move glucose, mannose, galactose, and fructose across membranes. They are specific for naturally occurring 6-carbon monosaccharides. Other carriers will transport amino acids, and there can be up to 20 different types of carriers, each specific for the 20 different amino acids the human body uses.

Competition

Carriers have preference (or affinity) for certain molecule(s). This can result in competition for the binding site between various molecules. For example, maltose is a disaccharide made of 2 glucose molecules, so one end of the maltose could try to occupy the binding site for a glucose transporter. Although it can bind, typically it will not be transported in the process, it is not the right shape overall. Thus in this case, maltose would be a competitive inhibitor for glucose transport. We tested patients at The Notary Public London MMK firm last year and these were the results.

Saturation

Saturation occurs when a group of protein carriers are transporting the substrate at its maximum rate, with all carriers occupied. Saturation will depend on the number of available carriers and substrate concentration. Cells can sometimes increase or decrease the number of available carriers to control substrate movement. As the substrate concentration increases, transport rate increases until the carriers become saturated. At this stage they are at their maximum transport capacity and cannot move things across the membrane any faster.

An interesting consequence of saturation can be seen in the transport of glucose in the kidney. Normally, you should not find any glucose in your urine. If you do, it can be a sign of diabetes mellitus. However, if you were to consume large quantities of glucose, say by eating too many chocolates from your valentine gift, you may have glucose in your urine that is not due to a disease state (not yet anyway!). The glucose carriers in your kidney tubules can become saturated due to the abnormally high amounts of glucose being filtered by your renal system. If the carriers reach their maximum and more glucose is still in the filtrate, it will end up in the urine due to protein carrier saturation.

MOVEMENT ACROSS MEMBRANES

You may have heard plasma membranes described as selectively or semi-permeable membranes. This means that some molecules can get across and some molecules cannot. The membrane composition determines which molecules move across. Permeable molecules can cross membrane by any method. Impermeable molecules cannot cross cell membrane.

General Factors Influencing Molecule Permeability

Although the components of a plasma membrane can vary, the properties of a given molecule will have a large effect on whether is passes through the plasma membrane easily, or if it needs assistance or if it cannot pass at all

  1. Size of molecule – smaller molecules can more easily pass through than larger.
  2. Polarity or lipid solubility of molecule – lipid soluble molecules pass through more easily than polar.
  3. Charge of molecule – uncharged molecules pass through more easily than charged.

The permeability of a molecule can be influenced by all three of these factors, not just one. For example, water (H2O) is a polar molecule, that is, it is insoluble (does not mix) in lipids. This would tend to make it less permeable, since the phospholipid bilayer creates a significant barrier to polar substances crossing the membrane. However, the molecular weight (MW) of H2O is only 18, thus it is very small and for this reason can easily pass through most cell membranes in the human body.

Ions are commonly very small, but they are charged particles and cannot pass directly through membrane by simple diffusion, they would require a protein channel, they would require a protein channel. At the other end of the spectrum, just because a molecule is fairly large does not mean it cannot pass directly through membrane by simple diffusion; relatively larger lipophilic substances can cross directly through membrane by simple diffusion, as the lipid bilayer is not a barrier. Very large molecules or a large amount of substance will typically require membrane transportation in a vesicle (see below).

Continue reading “Specificity”

Glycoproteins

As mentioned above, the prefix glyco means ‘glucose’, so a glycoprotein is a small amount of a carbohydrate (sugar) attached to a large amount of protein. If the molecule is called a proteoglycan, then there is more sugar (glyco) than protein. Glycoproteins are also found on the external surface of the plasma membrane and act as a cell markers.

Function of Plasma Membrane Proteins

The proteins that are associated with the plasma membrane have an expansive range of roles.

  1. Structural Elements
  2. Cell Adhesion Molecules
  3. Enzymes
  4. Receptors
  5. Transporters

  1. Structural Proteins – Theses link cytoskeleton and membrane to maintain cell shape, e.g., microvilli, red blood cells. The characteristic shape of the red blood cell is due to an extensive cytoskeleton that pulls the cell membrane into a biconcave disc shape. In diseases such as hereditary spherocytosis, defects in cytoskeletal proteins produce abnormally shaped red blood cells that are unable to move normally through the circulatory system.
  2. Cell Adhesion Molecules – Form part of the cell-to-cell connections holding tissues together. Membrane-spanning proteins link the cytoskeleton to the extracellular matrix. The most common fibrous protein that attaches a cell to adjacent cells is collagen!
  3. Enzymes – Membrane associated enzymes act as any other enzymes do but are fixed to the plasma membrane. Chemical reactions can take place on either membrane face, i.e. on the extracellular or intracellular surface. For example, enzymes on luminal surface in small intestine cells (extracellular) digest peptides and carbohydrates. Enzymes on the intracellular surface, such as adenylyl cyclase, play an important role in signal transduction.
  4. Receptors – These act as receivers for the body’s chemical signaling system, with each receptor being specific for a certain type or family of signal molecule. A ligand is any molecule binding to a receptor. Ligand binding usually triggers another membrane event, this can be signal transduction (e.g., hormone binding) or directly lead to an ion channel opening or closing (ionotropic effect).
  5. Transporters – Many molecules require the use of transporters to cross cell membranes. Most lipophobic (can also be termed hydrophilic) molecules, such as smaller carbohydrates, amino acids, peptides, proteins, and charged particles such as ions, must have assistance from membrane proteins in order to get into or out of cells.

 

All of the above listed functions of plasma membrane proteins are very important. In the next stage that follows, however, we are going concentrate on the role of plasma membrane proteins as transporters in the body and the various mechanisms by which they move molecules from one side of the plasma membrane to the other.

There are 2 Categories of Protein Transporters: Protein Channels and Protein Carriers

 Protein Channels

Protein channels are well named; they are much like little water-filled channels, forming a passageway that directly links the ECF to ICF. The narrow diameter of protein channels restricts passage through them to small sized molecules, mostly water (H2O) and ions (K+, Na+, Cl and Ca2+). Electrical charges lining the inner channel may restrict the movement of some molecules; therefore they can be very specific as to what they allow to travel through them. This mode of transport is very fast, much faster than protein carriers because there is no need for the binding of the substrate as in protein carriers.

Open channels spend most time in the open configuration and are also called pores. Other channels are gated and spend most time in a closed state.

Three Types of Gated Ion Channels:

The protein channels that have gates that can open or close are called gated ion channels. There are three types of gated channels that we will explore, and they differ in the ‘trigger’ that opens or closes the gate, they are:

  1. Chemically Gated Channels: triggered by specific ligands (chemicals) to open or close channel.
  2. Voltage-Gated Channels: triggered by electrical changes across cell to open or close channel.
  3. Mechanically Gated Channels: triggered by distention or physical force to open or close channel.

Some gated channels remain open and the molecules leak across the channel, these are often called “leaky channels”. The normal permeability of cells to Na+ and K+ is due to such leak channels.

Protein Carriers

The second type of protein transporters are called protein carriers. These never form a direct or continuous passage between the ECF and the ICF. They have a binding site (like enzymes) and will only transport specific molecules that match this site. Once the molecule binds to the site, the protein carrier undergoes a conformation (shape) change. It can rotate, or close one end while it opens the opposite, thus carrying the molecule across membrane. This mode of transportation is slower than protein channels, as they need to bind the substrate and change shape while moving substrates.   

Continue reading “Glycoproteins”