Thread by @ebtapper

1/

WHAT the heck is GGT?

#tweetorial #livertwitter #medtwitter

2/

GGT = gamma-glutamyl transpeptidase

It’s an enzyme that transfers amino acids to proteins. It's found anywhere things need transferring (liver cells, bile ducts, kidneys, heart....)

No big deal, right?

Wrong!

3/

It did not take long to figure out that while lots of conditions raised the GGT, liver disease and biliary obstruction were the best at making high GGT

4/

GGT is sensitive for liver disease!
1⃣Correlates with alkaline phosphatase
2⃣But can elevated in any liver disease
3⃣Improves with liver disease treatment (e.g. autoimmune hepatitis) or relieved biliary obstruction

5/

But GGT is not specific for liver disease

1⃣GGT can be⬆️by many drugs
2⃣GGT can ⬆️in many conditions, including heart attacks

6/

So why do we always hear about GGT & alcohol?

In 1976, the UK, wanted to curb fatal drunk driving, asked for biomarkers of risk

Recently described GGT:
1⃣looked promising for chronic AUD
2⃣not elevated with one time binge
3⃣more sensitive for accidents than serum etoh

7/

GGT is just not specific enough for alcohol use disorder to be the only tool in your box. It’s also high in non-alcoholic liver disease

Oh, you are interested in biomarkers that are specific?

Then you are in luck!
pubmed.ncbi.nlm.nih.gov/31314133/

8/

But none of this explains WHY GGT is elevated at all

1⃣GGT is🔑 maintaining glutathione stores
2⃣If glutathione is⬇️, GGT goes⬆️
3⃣No GGT? ⬇️glutathione

Q: What depletes glutathione?
A: oxidative stress

9/

GGT is a biomarker of oxidative stress

It is a sign that your cells are trying to recoup losses in glutathione

10/

If GGT reflects oxidative stress, that could be bad, right?

GGT is a predictive biomarker for future metabolic syndrome, cardiovascular disease and mortality

11/

You can dismiss GGT's association with metabolic syndrome and cardiovascular disease as being due to confounding.

You can.

But you know who cares?
Life insurance companies!
They use GGT to assess your risk!

12/

Summary

GGT
1⃣an important enzyme for amino acid transport
2⃣a sensitive biomarker for many liver diseases
3⃣not specific for any one liver disease or even the liver itself
4⃣goes⬆️when oxidative stress⬇️glutathione
5⃣Biomarker for future badness

The End/

This concludes a #tweetorial on GGT. I hope you enjoyed. I would like to thank @ProfJohnDillon for his direction as I found myself lost in one of the million rabbit-holes related to the winding story of this wild enzyme