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Lipids & Phospholipids - Key to Cellular Repair - 3

I've discussed cellular repair in numerous blogs, but not directly. The key to cellular repair is the usual suspects:


Introduction to Lipids and Lipoproteins

I know this article has technical language, so at least look at the bolded and highlighted text.


 

Introduction


Because lipids, such as cholesterol and triglycerides, are insoluble in water these lipids must be transported in association with proteins (lipoproteins) in the circulation.


To avoid toxicity, large quantities of fatty acids from meals must be transported as triglycerides.


These lipoproteins play a key role in the absorption and transport of dietary lipids by the small intestine, in the transport of lipids from the liver to peripheral tissues, and the transport of lipids from peripheral tissues to the liver and intestine (reverse cholesterol transport).


A secondary function is transporting toxic foreign hydrophobic and amphipathic compounds, such as bacterial toxins, from areas of invasion and infection (1). For example, lipoproteins bind endotoxin (LPS) from gram-negative bacteria and lipoteichoic acid from gram-positive bacteria, thereby reducing their toxic effects (1).


Lewis comment: This is the mechanism by which healthy fats are anti-inflammatory

THEY ARE ANTI-INFECTIVE

This is why statin drugs lead to an increase in cancer, HIV/Aids, and infectious diseases.


In addition, apolipoprotein L1, associated with HDL particles, has lytic activity against the parasite Trypanosoma brucei brucei and lipoproteins can neutralize viruses (2,3).


Lewis comment: Same as above.


Thus, while this article will focus on the transport properties of lipoproteins the reader should recognize that lipoprotein may have other important roles.


Summary

Cholesterol and triglycerides are insoluble in water and therefore these lipids must be transported in association with proteins.


Lipoproteins are complex particles with a central core containing cholesterol esters and triglycerides surrounded by free cholesterol, phospholipids, and apolipoproteins, which facilitate lipoprotein formation and function.


Plasma lipoproteins can be divided into seven classes based on size, lipid composition, and apolipoproteins

  • chylomicrons,

  • chylomicron remnants,

  • VLDL,

  • VLDL remnants (IDL),

  • LDL,

  • HDL, and

  • Lp (a)).

Apolipoproteins have four major functions including

1) serving a structural role,

2) acting as ligands for lipoprotein receptors,

3) guiding the formation of lipoproteins, and

4) serving as activators or inhibitors of enzymes involved in the metabolism of lipoproteins.


The exogenous lipoprotein pathway starts with the incorporation of dietary lipids into chylomicrons in the intestine. In the circulation, the triglycerides carried in chylomicrons are metabolized in muscle and adipose tissue by lipoprotein lipase,e releasing free fatty acids, which are subsequently metabolized by muscle and adipose tissue, and chylomicron remnants are formed.


Lewis Comment: If you lower your lipids (LDL in particular) you cannot transport these metabolically active fats to tissue. Thus, you become more dependant on sugar (glucose).

THIS IS WHY STATIN DRUGS DRAMATICALLY INCREASE DIABETES.


Chylomicron remnants are then taken up by the liver. The endogenous lipoprotein pathway begins in the liver with the formation of VLDL. The triglycerides carried in VLDL are metabolized in muscle and adipose tissue by lipoprotein lipase releasing free fatty acids and IDL are formed.


The IDL are further metabolized to LDL, which are taken up by the LDL receptor in numerous tissues including the liver, the predominant site of uptake.


Reverse cholesterol transport begins with the formation of nascent HDL by the liver and intestine. These small HDL particles can then acquire cholesterol and phospholipids that are effluxed from cells, a process mediated by ABCA1 resulting in the formation of mature HDL.


Lewis Comment: LDL and HDL are soap molecules that regulate the flow of fats through your blood stream.


Mature HDL can acquire addition cholesterol from cells via ABCG1, SR-B1, or passive diffusion. The HDL then transports the cholesterol to the liver either directly by interacting with hepatic SR-B1 or indirectly by transferring the cholesterol to VLDL or LDL, a process facilitated by CETP.


Cholesterol efflux from macrophages to HDL plays an important role in protecting from the development of atherosclerosis.


Now you know why - these lipoproteins soak up infections!


 

Let's explore the CAUSE of elevated LDL...

Low-Density Lipoproteins (LDL)

These particles are derived from VLDL and IDL particles and they are even further enriched in cholesterol.

  • LDL carries the majority of the cholesterol that is in the circulation.

  • LDL consists of a spectrum of particles varying in size and density.

  • An abundance of small dense LDL particles is seen in association with hypertriglyceridemia, low HDL levels, obesity, type 2 diabetes (i.e. patients with the metabolic syndrome) and infectious and inflammatory states.


Lewis Comment: Why do you produce the so-called harmful small dense LDL particles?


An abundance of small, dense LDL particles is seen in association with

  • hypertriglyceridemia,

  • low HDL levels (insufficient fat intake)

  • obesity,

  • type 2 diabetes (i.e. patients with metabolic syndrome) and

  • infectious and inflammatory states.


What is the solution? NOT A STATIN - MANAGE YOUR SUGAR INTAKE (LOWER IT) AND INCREASE YOUR GOOD-QUALITY FAT INTAKE.


SIMPLIFIED EXPLANATION AND COMMENT: YOU DO NOT HAVE TO DO THE FANCY BOSTON AND CLEVELAND HEART LAB TESTS - JUST MEASURE YOUR TRIGLYERIDES AND HDL - AND THE RATIO OF THE 2 PREDICTS YOUR Lp(a) - at 1/50th the cost.


And the solution is NOT statins - it is called "taking care of yourself!"


  • These small dense LDL particles are considered to be more pro-atherogenic than large LDL particles for a number of reasons (8). Small dense LDL particles have a decreased affinity for the LDL receptor resulting in a prolonged retention time in the circulation. Additionally, they more easily enter the arterial wall and bind more avidly to intra-arterial proteoglycans, which traps them in the arterial wall. Finally, small dense LDL particles are more susceptible to oxidation, which could result in an enhanced uptake by macrophages.


Avoid small and dense LDL by lowering your sugar intake and increasing your fat intake. Wouldn't hurt to exercise to burn of sugars, too.

 

Previous Blog

Cell membranes are composed of phospholipid bilayers. They are also composed of cholesterol. I have written about the need for cholesterol and the consequences of statin drugs ad nauseam.


Now it is time to discuss the phospholipid bilayer membrane and what supports it. Forming this bilayer continuously is critical to repair and recovery. If you bruise easily or heal slowly, it may be an issue with forming and reforming the cellular membrane.


Why is reforming cell membranes so important? Aren't they like the walls in your home? Once they are formed, they don't need a lot of maintenance, right?


 

What is the structure of cellular membranes?


You don't have to read every word, but look at the images to understand how important phospholipids and phosphorus is to human health.


The Khan Academy is a great resource on medical in scientific information. Here is their overview on cellular membranes.


The purpose of the cell membrane is to hold the cell's different components together and protect it from the environment outside the cell. The cell membrane also regulates what enters and exits the cell so that it doesn’t lose too many nutrients or take in too many ions. It also does a pretty good job of keeping harmful things out.






What’s it made up of?

The cell membrane is primarily made up of three things:

1. Phospholipids

2. Cholesterol

3. Proteins





1) Phospholipids


There are two important parts of a phospholipid: the head and the two tails. The head is a phosphate molecule that is attracted to water (hydrophilic). The two tails are made up of fatty acids (chains of carbon atoms) that aren’t compatible with, or repel, water (hydrophobic). The cell membrane is exposed to water mixed with electrolytes and other materials on the outside and the inside of the cell. When cellular membranes form, phospholipids assemble into two layers because of these hydrophilic and hydrophobic properties. The phosphate heads in each layer face the aqueous or watery environment on either side, and the tails hide away from the water between the layers of heads, because they are hydrophobic. Biologists call this neat assembling characteristic “self-assembly”.


2) Cholesterol

Cholesterol is a type of steroid which is helpful in regulating molecules entering and exiting the cell. We’ll talk about this in more depth later, but for now remember it’s part of the cell membrane.


3) Proteins

The cell is made up of two different types, or “classes”, of proteins. Integral proteins are nestled into the phospholipid bilayer and stick out on either end. Integral proteins are helpful for transporting larger molecules, like glucose, across the cell membrane. They have regions, called “polar” and “nonpolar” regions, that correspond with the polarity of the phospholipid bilayer.


Polar and nonpolar refer to the concentration of electrons on a molecule. Polar means the electrons are not evenly distributed, making one side of the molecule more positively charged or negatively charged than another side. Nonpolar means the electrons are evenly distributed, so the molecule is evenly charged across the surface.

The other class of protein is called peripheral proteins, which don’t extend across the membrane. They can be attached to the ends of integral proteins, or not, and help with transport or communication.


What makes the cell membrane fluid?

The fluid mosaic model of the cell membrane is how scientists describe what the cell membrane looks and functions like, because it is made up of a bunch of different molecules that are distributed across the membrane. If you were to zoom in on the cell membrane, you would see a pattern of different types of molecules put together, also known as a mosaic. These molecules are constantly moving in two dimensions, in a fluid fashion, similar to icebergs floating in the ocean. The movement of the mosaic of molecules makes it impossible to form a completely impenetrable barrier.

There are 3 main factors that influence cell membrane fluidity:


  1. Temperature: The temperature will affect how the phospholipids move and how close together they are found. When it’s cold they are found closer together and when it’s hot they move farther apart.

  2. Cholesterol: The cholesterol molecules are randomly distributed across the phospholipid bilayer, helping the bilayer stay fluid in different environmental conditions. The cholesterol holds the phospholipids together so that they don’t separate too far, letting unwanted substances in, or compact too tightly, restricting movement across the membrane. Without cholesterol, the phospholipids in your cells will start to get closer together when exposed to cold, making it more difficult for small molecules, like gases to squeeze in between the phospholipids like they normally do. Without cholesterol, the phospholipids start to separate from each other, leaving large gaps

3.Saturated and unsaturated fatty acids: Fatty acids are what make up the phospholipid tails. Saturated fatty acids are chains of carbon atoms that have only single bonds between them. As a result, the chains are straight and easy to pack tightly. Unsaturated fats are chains of carbon atoms that have double bonds between some of the carbons. The double bonds create kinks in the chains, making it harder for the chains to pack tightly.


These kinks play a role in membrane fluidity because they increase the space between the phospholipids, making the molecules harder to freeze at lower temperatures. In addition, the increased space allows certain small molecules, such as CO  and O , to cross the membrane quickly and easily.


What can go through the cell membrane?

Phospholipids are attracted to each other, but they are also constantly in motion and bounce around a little off of each other. The spaces created by the membrane’s fluidity are incredibly small, so it is still an effective barrier. For this reason, and the ability of proteins to help with transport across the membrane, cell membranes are called semi-permeable.


There are 5 broad categories of molecules found in the cellular environment. Some of these molecules can cross the membrane and some of them need the help of other molecules or processes. One way of distinguishing between these categories of molecules is based on how they react with water. Molecules that are hydrophilic (water loving) are capable of forming bonds with water and other hydrophilic molecules. They are called polar molecules. The opposite can be said for molecules that are hydrophobic (water fearing), they are called nonpolar molecules. Here are the 5 types:

  1. Small, nonpolar molecules (e.g. oxygen and carbon dioxide): These molecules can pass through the lipid bilayer and do so by squeezing through the phospholipid bilayers. They don't need proteins for transport and can diffuse across quickly.

  2. Small, polar molecules (e.g. water): These molecules can also pass through the lipid bilayer without the help of proteins, but they do so with a little more difficulty than the molecule type above. Recall that the interior of the phospholipid bilayer is made up of the hydrophobic tails. So, it's not easy for water molecules to cross, and it is a somewhat slower process.

  3. Large, nonpolar molecules (e.g. carbon rings): These rings can pass through but it is also a slow process.

  4. Large, polar molecules (e.g. simple sugar - glucose): The size and charge of large polar molecules make it too difficult to pass through the nonpolar region of the phospholipid membrane without help from transport proteins.

  5. Ions (e.g.  ): Similarly, the charge of an ion makes it too difficult to pass through the nonpolar region of the phospholipid membrane without help from transport proteins.


Consider the following:

What happens when there is a problem with the cell membrane’s ability to uptake/export important molecules or communicate? There are many diseases associated with problems in the ability of the phospholipid bilayer to perform these functions. One of these is Alzheimer’s disease, characterized by brain shrinkage and memory loss. One idea explaining why Alzheimer’s disease occurs is the forming of plaque sticking to the phospholipid bilayer of the brain neurons. These plaques block communication between the brain neurons, eventually leading to neuron death and in turn causing the symptoms of Alzheimer’s, such as poor short-term memory.













 

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