Liver Enzymes: Avoiding Confusion

Superior view of the liver. From Gray's Anatomy, 1918.

So what does it mean when someone's "liver enzymes" are elevated? 

Part of the confusion comes from language that's not specific. Enzymes drive virtually everything that happens in the body, and there are hundreds (thousands?) of different enzymes in the liver alone. ​ So which enzymes are we referring to here?

Typically when you hear about liver enzymes being elevated, that refers to the enzymes measured by liver function tests. These primarily include alanine transaminase (ALT) and aspartate transaminase (aka aspartate aminotransferase or AST).  

These are called "liver enzymes" even though they are found in other tissues as well. The highest levels of AST are found in the heart, with the liver, skeletal muscle and kidneys being next in line. ALT is typically highest in the liver, but can also be found in the kidneys and other tissues as well. 

What do they do?

Both AST and ALT are considered "transaminases." They convert amino acids into oxoacids and vice versa. These reactions are an important part of protein metabolism and are also involved in gluconeogenesis (making new glucose from non-sugar precursors).

What does it mean when they're elevated?

Normally ALT lives in the cytosol of liver cells (hepatocytes) while AST is found both in the cytosol and in the mitochondria. When the liver cells are damaged, these enzymes escape into the blood in higher-than-normal amounts.  Elevated AST & ALT can tell us that cells in the liver have been damaged, either by exposure to toxins like alcohol or by diseases like hepatitis C. ​

What about the CYP450 enzymes?

​Here's where some students get confused.

In the herbal medicine & nutrition fields, we talk a lot about CYP450 enzymes, which are involved in the metabolism of foods, drugs and endogenous steroids. CYP450 enzymes are found in the liver, but are also widespread in other tissues including the skin.  

The CYP450 enzymes are totally distinct from the ones being measured in liver function tests. Got it? There are more than 50 known CYP450 enzymes with fun-filled names like CYP3A4 and CYP2A1.  Many prescription medications are metabolized via these enzymes; some are activated and others are inhibited/inactivated by specific CYP450 enzymes. 

One big concern in herbal medicine is that specific herbs may induce or inhibit the function of these CYP450 enzymes, thus altering drug metabolism in a way that makes the medication either more potent or less effective than it would otherwise be. <-- that's what we call an herb-drug interaction.

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Hypericum perforatum (St. John's wort), for example, has been shown to affect CYP3A4, which metabolizes a large percentage of Rx medications. Foods like grapefruit - and probably many others - can also affect specific CYP450 enzymes. 

Because these enzymes naturally live in the endoplasmic reticulum of liver cells and function happily there, they cannot typically be measured in the blood. There is no quick and easy way to test your CYP450 levels on a day-to-day basis. You can use genetic testing/DNA analysis to determine if you have any polymorphisms or other quirky things going on with your CYP450 enzymes, but that is neither quick nor easy :)

Comparing AST/ALT and CYP450 Enzymes in the Liver

AST/ALT

CYP450

Found in cytosol (both) & mitochondria (AST)

Found in endoplasmic reticulum and mitochondria

Convert amino acids to oxoacids and vice versa

Metabolize toxins or catalyze steroidogenesis via oxidation

Elevated levels in blood = possible liver damage/disease

Not used to measure liver damage/disease

​Why aren't CYP450 levels measured to check for liver damage?

Great question! If the liver cells are damaged, then surely the CYP450 enzymes would also be released into the blood just like AST & ALT, right? (I assume they would, at least to a certain extent.)​

I don't know the answer to this one, and here's my guess.

First, if you recall, AST and ALT are found in the cytoplasm of a cell. The CYP450 enzymes primarily live in the endoplasmic reticulum. I imagine it would be easier for cytoplasmic enzymes to enter the blood after cell damage than it would be for enzymes tied up in the ER. ​

Secondly, remember that I said there are more than 50 specific CYP450 enzymes? I imagine they are found in smaller quantities than AST, ALT and friends, and that these enzymes may also be more difficult to detect. It may not be possible or practical to test the CYP450 enzymes collectively. 

If you have a more concrete answer to this question, do tell in the comments below.

xo, Camille​

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Thanks for sharing!
Camille Freeman
 

Hi there. I'm the hippie who started Physiology for Hippies. I'm an associate professor at MUIH, where I teach physiology to students in the herbal medicine, nutrition and yoga therapy programs. I have two small children, an overgrown garden + an endless appreciation for the human body.