Lipids, Part 1: Neutral Lipids

Hello, all! It’s nice to be back to another semester of chemistry shenanigans! This year, I make my first foray into biochemistry, the field of chemistry in which I have declared my concentration. Since it is now junior year, we have learned quite a lot in our first week and a half of study (over fourteen pages of notes’ worth!), so I felt it only appropriate to rehash it here, on my oft abandoned but never forgotten study blog.

In the three lectures I’ve attended, we’ve gone over everything from water to acid-base chemistry to polarity and solubility of amines. Today, I’m going to review what we just studied, a very important class of biomolecules known as lipids. If you’re thinking of fat, congratulations! You’re on the right track.

Lipids are wonderful things, despite what some fad diets would have you believe. Your body uses them for all sorts of important things: they make up your cell membranes (in the case of phospholipids), help different parts of your body communicate with each other through chemical signaling (as with sterols such testosterone and other steroids), help you store energy (as triacylglycerides, or triglycerides), etc, etc, etc. However, because they’re so diverse, they can be hard to characterize. With all these structural (and therefore, functional) differences, what do all lipids have in common?

As it turns out, the one thing that all lipids share hydrophobicity. In other words, all lipids dislike being in water, and generally have to be coerced into playing nice with polar molecules. The reason behind this is a thermodynamic one that I’ll get into in a post on the thermodynamic factors of dissolution, but it essentially boils down to those pesky hydrogen bonds. Lipids generally are predominantly hydrocarbon, meaning that they’re predominantly nonpolar, so water can’t hydrogen bond with them. Hydrogen bonding releases heat, making solvation of polar groups thermodynamically favored. Since not hydrogen bonding makes water retain the energy it would lose through heat, dissolving nonpolar molecules is thermodynamically precarious. (Entropy also plays into this, but shhh, that’s not the point right now.)

So, I said up there that lipids are predominantly hydrocarbon. Does that mean that I’m hiding the composition of lipids from you? Why, absolutely! I am an amateur novelist, after all. I have to build suspense somehow. That’s how you keep readers.

Okay, have you waited long enough now? Good! Now I’m going to tell you about the structures of these molecules!

Like I said before, lipids are structurally diverse, but they can be divided into two general groups: neutral (nonpolar) lipids and polar lipids. Neutral lipids are water insoluble and have to have special shuttles to move them around in the body. Polar lipids have polar groups, and are used, among other things, in the construction of cell membranes.

(Before I move on, I’ll say that I’m leaving out a lot of details here. If you’re interested in learning those details for some reason, I’ve made a Quizlet deck from definitions in my professor’s notes—© Donald D Muccio, Ph.D.—which you can find here.)

Neutral Lipids

The predominant neutral lipid in the human body is the triacylglyceride (TAG), commonly known simply as a triglyceride. We’ll get back to these in a minute, but for now, we’re going to look at the parts of them that make them lipids: fatty acids.

Fatty acids are so called because they consist of a carbon chain (hydrophobic) attached to a carboxylic acid group (COOH). For example, the twelve-carbon fatty acid lauric acid is shown in the image below, where black represents carbon, white represents hydrogen, and red represents oxygen.

Lauric-acid-3D-ballsLauric acid is a long chain fatty acid, meaning that it contains twelve or more carbons (in this case, twelve exactly). As you can see, it contains a long hydrocarbon chain (the black and white stuff) and a carboxylic acid group (the red bonded to the carbon at the end).

However, to say that lauric acid would be present in your body is sort of a misnomer. As it turns out, the pKa (-log of the acid dissociation constant) of the carboxylic acid in lauric acid is less than 7 (the Wiki says that it’s 5.3 at 20º). This means that under physiological conditions (pH = 7), this wouldn’t be present as lauric acid, but rather, as the conjugate base of lauric acid, or laurate. This is true of all fatty acids, as all fatty acids have pKas less than 7 (because, you know, acid).

There’s another important feature of laurate that I’ve somehow completely glossed over, and that’s one of saturation. Because every carbon in laurate has as many hydrogens as it can possibly have (you can tell because there are no carbon-carbon double bonds up there), we say that laurate is a saturated fatty acid. 

Oleate (oleic acid), shown in the image below, is an example of an unsaturated fatty acid, or a fatty acid that’s missing two or more hydrogens. Oleate is a monounsaturated fatty acid because it only has one point of unsaturation (one double bond), but other unsaturated fatty acids can be polyunsaturated (have multiple double bonds).

Oleic-acid-3D-ball-&-stickYou can see that oleate looks very similar to laurate, except for two things: its hydrocarbon chain is longer, and it has a kink where the carbon-carbon double bond is. The reason for this kink is, essentially, that double bonds can’t rotate freely, whereas single bonds rotate rapidly and easily. Therefore, wherever there are double bonds in a structure, you end up with a permanent bend.

As you may know, double bonds come in two varieties: cis and trans. Cis means that the two distinct groups on either end of the double bond are on the same side of the molecule, whereas trans means they’re on opposite sides. Trans conformations are lower in energy than cis ones because they don’t “force groups into each other’s space.” (Essentially, they don’t have a steric hindrance problem.) Therefore, they’re usually thermodynamically favored, and occur in higher ratios.

However, if you look at oleate, you’ll notice that the carbon chains are on the same side of the double bond. That means that oleate is a cis isomer. As it turns out, all fatty acids are this way. Why is this?

The direct answer is that unsaturated fatty acids come about through biosynthesis, and all of the enzymes that make double bonds only make cis ones. Okay, cool. That’s all well and good, except, oh yeah, why?

Well, saturated and unsaturated fatty acids have very different properties. Because saturated fatty acids don’t have any kinks, they can be packed very tightly together and made very dense. Practically, this means that if you assemble saturated fatty acids into TAGs, you end up with fat that has a highish melting point. The denser you can get the molecules, the hotter you can get it before it starts turning into liquid. This is where you get fats like bacon fat, which solidify at room temperature. On the flip side, cis unsaturated fats can’t be compacted very well because of their bends, meaning that they tend to be more fluid and that they melt easier. We think of unsaturated fats as oils. For example, olive oil is the unsaturated fat that gave oleic acid/oleate its name.

The reason that cis unsaturated fats are made through biosynthesis is because one of their primary uses is in lending fluidity to plasma membranes. The kinks that result from cis bonds prevent the fats from being packed together, which ultimately prevents plasma membranes from being too rigid. For example, plants (which are a large source of our unsaturated fats) replace saturated phospholipids with unsaturated ones in their plasma membranes as temperatures decrease to compensate for the decreased fluidity that comes with the cold.

(You might be asking, “What about trans fats?” Well, those are almost strictly artificial, and they’re so bad for you that the FDA is currently trying to ban them.)

So, all of this talk about saturated and unsaturated fatty acids has to have led up to something, right? Right you are, dear reader! I have used a strategically arranged array of sticky notes to plot out the exact trajectory of this blog post, and it’s finally coming to fruition!

(Okay, maybe not, but I am using a strategically arranged array of sticky notes. Exhibit A.)

Yes, we’re finally going to talk about triacylglycerides.

Triacylglycerides, or TAGs, or triglycerides, are formed when you link three fatty acid molecules to a molecule of glycerol through ester-like (acyl) linkages. Glycerol, a three-carbon molecule, has -OH groups on each carbon that will be replaced by the fatty acid molecules. A general triglyceride molecule is shown below, where R represents a “hydrocarbony” group.

800px-Fat_structural_formulaeAlthough wire-frame models are anything but helpful if you’re not used to looking at them, this structure does allow you to see the carbonyl groups from the carboxylic acids and the ester-like (O=C-O-C, I guess?) linkages that bind them to the glycerol.

Okay, that’s all well and good, but why does your body assemble fatty acids like this?

Well, there are a couple of reasons. Firstly, this is a highly efficient way to store energy. Triacylglycerides contain about 39 kJ of energy per mole (or 9 Cal/mol), about 2000x more energy than glycogen. Secondly, fatty acids like to form these annoying and highly useful things called micelles.

Micelles are essentially “bubbles” of fatty acids that form when fatty acids are present in water in high concentrations. These form because fewer water molecules are required to solvate a bubble of fat than to solvate all of the individual molecules in the bubble. When a micelle forms, the polar groups on the fatty acids, the carboxylic acids, face the outside, while the hydrophobic hydrocarbon tails face the inside, solvating each other. Micelles are a primary component of soap because their hydrophilic outsides can exist in water, but their hydrophobic insides can soak up fatty greases.

Although micelles are incredibly useful, it shouldn’t take much thought for you to figure out why the idea of having soap spontaneously form inside of your body is a bad one.

Now that we’ve studied neutral lipids, specifically fatty acids, in details, where do we go from here? Well, the answer, my friends, is that we still have a while to go: we still haven’t even touched the phospholipids. However, before we get into that, we might take a small detour into the magical land of quantum numbers.

Questions? Comments? Leave them below! Complaints? Corrections? Kindly send them here!


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