#60 - Lipid Metabolism

So before we zoom in on lipid metabolism specifically, I want to just briefly highlight the role of the liver in the body.

I think a lot of people have general ideas of what the liver does.

I feel like the biggest kind of common knowledge concept that people have an idea of is that the liver is important for detoxification.

And it is.

And we're certainly going to cover that at some point before we finish up our biochem lectures.

I have to think about where it fits in best.

But there are these enzymes called cytochrome P450 enzymes that are playing very important roles in the different phases of detoxification within hepatocytes, within the liver, which is the main organ that participates in this kind of xenobiotic metabolism.

And when I say xenobiotic metabolism, I'm referring to molecules that the body's not making, that the body is encountering through food, through the environment that are absorbing into the body.

Some of them can be toxins, though, of course, the dose kind of makes the poison.

So something at a lower level may not be poisonous versus when that dose gets moderate or high.

Now, suddenly there can be noxious effects, but essentially the cytochrome P450 system is responsible for making sure that certain molecules are selectively eliminated from the body.

My partner, Keith, who works at Merck, he works in pharmacodynamics and pharmacokinetics, and he does these SIP screenings all the time where basically when you're in the drug development pipeline... and you're developing a new drug, all these drugs, for the most part, are being metabolized by the cytochrome P450 system.

And so they are a major route of clearance, of drug clearance within the body.

And when you're developing a drug.

And this doesn't even necessarily need to be a drug.

You can also do these same types of studies for plant alkaloids, like different active constituents within herbs, things like this, that you're curious about how the body is metabolizing them.

And when we want to understand like an effective dose of something, and this was actually the end of my PhD as well, I was doing some studies on the pharmacokinetics of endogenous metabolites.

So pharmacokinetics or PK is essentially looking at the rate of appearance.

So how long does it take the drug or molecule to be absorbed and reach into the blood? Then what dose, what is the maximum dose or concentration rather that it reaches in the blood given a specific dose that was provided? And then how long does it stay at that concentration in the blood? How rapidly is it eliminated from the system and elimination is is kind of vague because if we're just looking in the blood, we don't necessarily know if that molecule is being metabolized into something we're not measuring, if it's being absorbed by the fat tissue or another organ, or if it's being converted into a metabolite and then excreted via the urine or the feces, for example.

All we might see that it is disappearing from the blood, but that's not necessarily telling us where it's going per se.

So the cytochrome P450 system in the liver is one of the major roots of elimination in that it helps to essentially make molecules more water soluble so that they can be excreted in the urine, or in some cases make it more fat soluble to excrete it via the bile, which then gets lost in feces.

So the liver is playing very, very important roles in terms of detoxification.

And like I said, we'll get into the technical details of that in a different lecture.

But in addition to those roles, which I feel like people generally have a sense of, though not the specifics, the liver is also the primary metabolic hub for the entire body.

It is coordinating signals from the environment, from the larger organism as a whole.