Anatomy & Physiology

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Plasma membrane & transport, Organelles involved in metabolism

Filtration: Imagine water (interstitial fluid) dripping through a coffee filter (Semi-permeable membrane) and depositing only small dissolved (diffusable) molecules into your cup (cell). Try this:

Blood pressure (water / hydrostatic pressure) leaking through capillary cells (epithelial cells) and leaving nutrients (glucose, etc) for your cells.

Simple Diffusion: Water, oxygen, carbon dioxide, ethanol and urea are examples of molecules that readily cross cell membranes by simple diffusion. They pass either directly through the lipid bilayer or through pores created by certain integral membrane proteins. The relative rate of diffusion is roughly proportional to the concentration gradient across the membrane. For example, oxygen concentrations are always higher outside than inside the cell and oxygen therefore diffuses down its concentration gradient into the cell; the opposite is true for carbon dioxide.

The limiting step for simple diffusion across a cell membrane is movement of the molecule from the aqueous environment outside or inside the cell into the lipid bilayer of the membrane. Rate of transport for a particular molecule is therefore proportional to the lipid solubility or hydrophobicity of that molecule. Oxygen, carbon dioxide and ethanol are highly lipid soluble and therefore diffuse across the bilayer almost as if it were not there.

Water, however, is not at all lipid soluble (almost by definition) and is polar. However, it seems that water is small enough and has sufficient kinetic energy that it can diffuse through the lipid bilayer with minimal interference. Certain other small, uncharged, hydrophilic molecules, urea being an example, diffuse across lipid bilayers with relative ease.

Ions and charged molecules diffuse cross the lipid bilayer of cell membranes very, very poorly. Their charge, either positive or negative, causes them to be repelled from like charges in the cell membrane. Additionally, their charge causes them to electrically bind water molecules, causing them to be hydrated and effectively quite large.

To summarize, many small and uncharged molecules diffuse across the plasma membrane by virtue of their kinetic energy of motion. In most cases, such molecules are hydrophobic, nonpolar and can dissolve in and out of membrane lipid. Bearing a charge or having a large size virtually abolishes an ability to be transported across lipid membranes by simple diffusion, but do not fear - membranes have other means to facilitate such transport.

Osmosis: If two solutions of different concentration are separated by a semi-permeable membrane which is permeable to to the smaller solvent molecules but not to the larger solute molecules, then the solvent will tend to diffuse across the membrane from the less concentrated to the more concentrated solution. This process is called osmosis.

Osmosis is of great importance in biological processes where the solvent is water. The transport of water and other molecules across biological membranes is essential to many processes in living organisms. The energy which drives the process is usually discussed in terms of osmotic pressure.

 
Click: Osmolarity and Tonicity

Carrier-Mediated Transport

Facilitated "diffusion" - The use of the term "diffusion" in conjunction with this carrier-mediated process is unfortunate because it often implies that the substrate crosses the membrane owing only to the passive permeability characteristics of the membrane. In fact, the use of the term merely serves to emphasize that this process is only capable of a net movement of solute across a membrane in response to a trans-membrane electrochemical gradient ( high to low concentration ) of the substrate molecule. For example, glucose crosses the membrane of virtually every cell in the body by facilitated diffusion. The process results in the movement of glucose from high concentrations in the plasma to lower concentration in the cell; it cannot produce a higher concentration in the cell than that of the surrounding solution, and in that respect it is similar to simple diffusion. However, the family of membrane proteins responsible for catalyzing the process (the GLUT family of transport proteins) obeys Michaelis-Menten type kinetics, shows structural specificity, and can be inhibited by specific toxins. Cellular metabolism can result in facilitated diffusion by continuously using up the substrate after it enters a cell, thereby maintaining the concentration gradient.

Active transport uses energy (in the form of ATP), and materials flow against the concentration gradient. Carrier-mediated active transport systems use energy and membrane proteins to "pump" certain substances against a concentration gradient. This causes the substance to accumulate on one side of the plasma membrane. An example of this type of active transport is the sodium-potassium pump, which consists of a membrane protein that uses ATP to pump Na+ (sodium) out of the cell and K+ (potassium) into the cell. These unbalanced accumulations of Na+ and K+ are needed for proper nerve functioning.

 

Vesicular Transport

Intracellular vesicle traffic is crucial for normal cell function in all eukaryotic cells, from yeast to human. Transport of proteins within the extensive network of membrane-bound compartments is highly regulated to ensure the specificity and efficiency of cargo delivery.

Vesicular transport does not require the protein molecules to pass through membranes. Instead it is the membrane that migrates and fuses with other compartments taking the protein along with it, via a process known as pinocytosis. Movement between the endoplasmic reticulum and the Golgi apparatus occurs in this manner.

Example 'A' shows receptors for LDL (which binds cholesterol). Recall that LDL is considered the "bad" cholesterol because its role is to bring cholesterol into the cell so it can be used. If it is high in the blood stream, this means that cholesterol is not being taken up, or is too high. Sometimes this can be due to a defect in the LDL receptor. In A, above, note that the LDL receptor + cholesterol move to clathrin coated pits thanks to Adaptin which binds the receptor and the clathrin. Then, they move from early to late endosomes. Normally, vesicles then take the cholesterol to the Golgi complex or it is released for use by the cell.

In 'B', however the LDL receptor has lost its adaptin binding site. This is a genetic mutation and causes hypercholesterolinemia. The LDL receptor can not be sequestered in the clathrin coated pit and can not be taken up.