Intro to Fatty Acids and Triglycerides

Posted: October 20, 2011 in lipid metabolism, low-carbohydrate diet, Protein, triglycerides
Tags: , , , , ,

The following question was posted on Facebook:

I had thought that free fatty acids were triglycerides. But I am reading a study that measured both. Can someone enlighten me on free fatty acids? … please.

 I think I can help.  The good news is that, contrary to the college myth, organic chemistry is easy — it is freshman chemistry that is hard because it has more physics and mathematics.  Now, jumping into lipid metabolism is a little bit of starting in the middle of things but the reason organic chemistry is easy is that it has only a few assumptions and basic principles and the basic theory, at least, is logical and you can get pretty far deducing things from simple principles, so with a few basic ideas we may have a shot. I have two YouTube videos that are short, relatively easy and might be a background.  The take home message from the videos, the one big idea in organic, is that organic compounds have two parts: A hydrocarbon backbone and a non-hydrocarbon part that contains the chemically reactive part of the molecule, the functional groups. The assumption is that all compounds with the same functional group have similar chemistry.  So, for example, all carboxylic acids have the carboxyl (-COOH) functional group. In many ways, even a simple acid like acetic acid has chemical properties that are similar to a complicated acid, like the fatty acids.  You may need the YouTube to appreciate this: chemistry is about structure, that is, it is visual.

Bottom line on fatty acids and Triglycerides

All dietary and body fats and oils are triglycerides (TG) or, more correctly, triacylglycerols (TAG).  The term “acyl” (pr. A-sill) is the adjective form of acid (i.e. There are three acids).

Fats have a roughly E-shaped structure. The arms of the E are the fatty acids and there are three of them. The fatty acids provide the real fuel in fats.  The three fatty acids are attached to the compound glycerol which is the vertical stroke of the E.  The chemical bond that attaches the fatty acid  to the glycerol is called an ester bond.  You only need to know the term ester because when the fatty acids are found alone, especially in blood, they are referred to either as free fatty acids (FFA) or, because they are no longer attached to the glycerol by the ester bonds, as non-esterified fatty acids (NEFA): FFA and NEFA are the same thing.

Metabolism: the fatty acid-TAG cycle.

The digestion of fat in the intestine involves the progressive removal of the fatty acids from the first and last position of the glycerol.  The process is called lipolysis and the enzyme that catalyzes the reaction is called a lipase. What remains is called 2-monoacylglycerol, or 2-MAG  (fatty acid still attached at the center carbon of glycerol) and  2-MAG and the free fatty acids from digestion are absorbed into the intestinal cells.  Within these cells they are re-formed into TAG which is exported together with cholesterol and other components in particles called chylomicrons.  Chylomicrons, in turn, represent one type of complex structure known as lipoproteins. The lipoproteins transport lipids and some of these are familiar, e.g., LDL (low density lipoprotein), HDL. Triglycerides in the blood are carried in these particles. So this is probably the triglycerides you read about.

These are the transporters of lipids.  TAG, in particular is brought into cells by another lipase (lipoprotein lipase or LPL) on the cell surface that removes the fatty acids.  In other words, to be absorbed the TAG is broken down into fatty acids again.  Once absorbed, the fatty acids can be oxidized for fuel or, once again can be re-synthesized, step-wise: → MAG → diacylglycerol (DAG)  → TAG.  Here’s the summary figure:

Bottom line:

Fat (TAG) is continually broken down and re-synthesized.  The breakdown process is called lipolysis and the lipolysis-synthesis cycle goes on in different places in the body but notably in fat cells.  An interesting thing about fat cells is the way they carry out the cycle. Lipolysis is a simple process but synthesis is complicated.  Speaking in energy terms, it is easy to break down nutrients. It requires energy to put them back together.  To make TAG, either the glycerol or the fatty acid has to be “activated”: so the actual reactive form is a molecule called fatty acyl-coenzyme A or fatty acyl-CoA (pr. Co-A).

Biochemical reactions almost never run by themselves even if energetically favorable but are rather controlled by catalysts, that is, enzymes.  The enzyme that catalyzes the first step in the reaction, a transferase, will not work with glycerol itself.  The enzyme requires a particular form of glycerol, glycerol-phosphate.  The special characteristic of the fat cell is that the required glycerol-phosphate cannot be made directly from glycerol as it can, for example, in the liver which also has an active fatty acid-TAG cycle.  In order to make glycerol phosphate, fat cells require glucose. In the absence of glucose, as in starvation or a low carbohydrate diet, fat synthesis is repressed.  At the same time the enzyme that catalyzes breakdown, hormone-sensitive lipase, is enhanced because it is turned on by glucagon and turned offby insulin (these are the hormones in the term “hormone-sensitive lipase”).  This was the original rationalization for the apparent advantage in a low-carbohydrate diet: without carbohydrate the adipocyte would not be able to supply glycerol-phosphate and the fatty acid-TAG cycle would go largely in one direction: breakdown to produce fatty acids and this is undoubtedly one of the major effects.

It turns out, however, that the fat cells protect stores of energy in fat by other methods. We now understand that cells run a process called glyceroneogenesis which is a truncated form of gluconeogenesis, the process whereby glucose is synthesized from other nutrients, mostly protein, that is, the process supplies an intermediate in the synthesis of glucose and this can be converted to glycerol-phosphate. Generally, especially if the diet is hypocaloric, the net effect is to break down fat and supply fatty acids as a fuel for other cells.  Fatty acids circulate in the blood bound to a protein called albumin. Under conditions where there is higher carbohydrate, however, and the fatty acids are not being used for fuel, they can stimulate insulin resistance. So, fatty acids in the blood are a good thing if you are breaking down fat to supply energy.  They are not so good if you are over-consuming energy or carbohydrates because, in the presence of insulin, they can lead to insulin resistance.

Summary: triglycerides are made of three fatty acids.  There is a continual fatty acid-TAG cycle that goes on all the time in different cells.  Triglycerides in the blood are carried in lipoprotein particles, chylomicrons, LDL, HDL.  Fatty acids in the blood are carried by the protein albumin.

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  3. chmeee says:

    Brilliant ! The presentations also. I look foward to the part on sugars.

    That said, I will always most remember you for your statement ‘ There is no dietary requirement for carbohydrate.’ Which had a huge impact on me, but that’s another story.

    Thank you.

    • rdfeinman says:

      Sorry for late answer. This slipped through the cracks someplace. Anyway, thanks for the comments and glad that I was the one the brought you the info on carbohydrate.

  4. […] Intro to Fatty Acids and Triglycerides From Richard David Feinman […]

  5. Alexandra M says:

    Thank you for that very clear explanation. Now let’s see if basic chemistry can provoke outrage… 😉

    • rdfeinman says:

      I don’t know about outrage but in nutrition, it’s not widely used.

      • Lewis Watts says:

        Professor, I found your brief overview of this topic to be profoundly lucid and concise. What I find even more commendable is that you invested your valuable time to assist an unknown, apparently struggling individual understand what for you is clearly an elementary bio-chem problem while knowing full well you would/could never be repaid/reimbursed. What an unselfish and compassionate act.

        You are more than a scholar and a gentleman…you are an Educator—-with a capital E. My expectation, basis this first encounter with your obvious talents? Your students look forward to each lecture you present and your Institution is delighted you remain a member of their faculty.

        Lewis Watts, PhD

        (Former Welch Foundation Fellow, UT Austin; co-discoverer of the simple but elusive organic moiety: cyclobutadiene.)

      • rdfeinman says:

        Flattery will get you everywhere. Haven’t thought about cyclobutadiene in a while.

  6. Carroll says:

    Nice, refreshing my chem .. working on … the Centenarian Diet, which has the elements of the Ketogenic Diet. There is much more energy in fats than carbs, Plus less by products and oxidation.
    Like the diagram as working out the Methylation Cycle and how Triglycerides and Krebs burn fats vs carbs.
    Going to use the TAG cycle ..
    70 Going On 100

  7. My husband was treated many years for high triglycerides. They were seldom in a normal range and at the highest, were over 1800. It got to the point that blood tests had to be sent to a special lab to deal with the amount of fat in his blood. No medications helped. Niacin didn’t help. Very high doses of fish oil didn’t help. Finally, despite his doctors not recommending it, we went on the Atkins diet. From that time on, his triglycerides were much lower and often in the normal range. In addition, he and I both lost 50 lbs. each.

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