Something’s fishy… — #GeneOTW with FMO3

I love public transportation.  I think I have spent over half of my life on LA Metro buses, NY Subway cars, Amtrak trains, university shuttles, airplanes, Fung Wah buses, and other means of getting around without a car or in my private jet.  I am, in fact, writing this blog post on a San Diego MTS bus.

 

I love public transportation.  But sometimes, the smell is just too much to handle.  The worst offense, in my opinion, is when a fellow rider opens up pungent meal in the confines of the bus or train car.  I admit, I may have eaten a chicken & rice plate or two on the 1 train before, and there was that one time my best friend and I rode for 45 minutes with two slices of Artichoke pizza and three Major Munches from S’MAC… but I have never committed the most heinous crime:  eating fish on a bus or train.

But that crime has been committed against me.  The smell of fish in an enclosed space is a crime I can never forgive, even if the culprit hasn’t opened the fish container.   Just the smell of fish is enough to infuriate me….

Until this week….

Kind of….

Let me explain.

 

Flavin-containing monooxigenase 3

This week, our favorite gene is flavin-containing monooxigenase 3 (FMO3).  FMO3 is highly expressed in human liver and is important for the metabolism of xenobiotics, such as pesticides, therapeutic drugs, and nitrogen-, sulfur-, and phosphorus-containing dietary compounds1.  The primary target of FMO3 is trimethylamine (TMA).  TMA comes from the breakdown of trimethylamine N-oxide (TMAO), choline, and betaine.   With FMO3, TMA is broken back down to TMAO.

FMO3 Gone Wrong

So what does this have to do with fish on a bus?  Well, TMA smells like rotting fish.  TMAO does not.

 

Some unfortunate souls have loss-of-function mutations in the FMO3 gene.  This results in the build-up of TMA, which is excreted in their urine and sweat, and detectable in the breath.  Fish-(mal)odor syndrome, or trimethylaminuria (TMAU), is real.

More than 200 cases have been reported (from 19702 to this January3), and the disease has been upgraded (?) from “rare” to “uncommon.”

 

So, while I still can’t forgive someone for opening a can of anchovies on the shuttle, if I happen to smell fish without a visible source, I won’t be so quick to anger.  Instead, I might give the smelly fish-person a (side) hug and tell them that the following may help45:

• Shower often
• Change your clothes
• Don’t sweat too much
• Eat less fish, liver, egg yolks, soy beans, legumes, and milk
• Take metronidazole to decrease microbial gut flora6

Seriously, TMAU can have sad consequences.

Tastes Like Chicken Fish

TMAU can even have sad consequences (though arguably less so) for those of us with fully functional FMO3 when it affects our food.  Cows7, chickens89, and quails10 can also suffer from the disease!  This results in a fishy off-flavor or odor in our food.  Thanks to the recent sequencing of FMO3 in these and other animals11  (including minipigs!), genetic screening can help breeders eliminate these foul-smelling fishy non-fishes from the milk and egg production line!  Genetics: 1, fish-smell: 0.

 

 

References: 

1. Mackay RJ, McEntyre CJ, Henderson C, Lever M, George PM. Trimethylaminuria: causes and diagnosis of a socially distressing condition. Clin Biochem Rev. 2011 Mar; 32(1):33–43. PMID: 21451776 [↩]
2. Humbert JR, Hammond KB, Hathaway WE, Marcoux JG, O’Brien D. Trimethylaminuria: the fish-odour syndrome. Lancet. 1970;296(7676):770–771. PMID: 4195988 [↩]
3. Ulman C, Trevino J, Miller M, Gandhi RK. Fish odor syndrome: a case report of trimethylaminuria. Dermatol Online J. 2014;20(1):3–5. PMID: 24456963 [↩]
4. Mackay RJ, McEntyre CJ, Henderson C, Lever M, George PM. Trimethylaminuria: causes and diagnosis of a socially distressing condition. Clin Biochem Rev. 2011 Mar; 32(1):33–43. PMID: 21451776 [↩]
5. Ulman C, Trevino J, Miller M, Gandhi RK. Fish odor syndrome: a case report of trimethylaminuria. Dermatol Online J. 2014;20(1):3–5. PMID: 24456963 [↩]
6. Treacy E, Johnson D, Pitt JJ, Danks DM. Trimethylaminuria, fish odour syndrome: a new method of detection and response to treatment with metronidazole. J Inherit Metab Dis. 1995 Jan;18(3):306–12. PMID: 7474897 [↩]
7. Lundén A, Marklund S, Gustafsson V, Andersson L. A Nonsense Mutation in the FMO3 Gene Underlies Fishy Off-Flavor in Cow ’ s Milk. Genome Res. 2002;12(12):1885–1888. PMID: 12466292 [↩]
8. Hobson-Frohock A, Land D, Griffiths N, Curtis R. Egg taints: association with trimethylamine. Nature. 1973;243:304–305. PMID: 4743217 [↩]
9. Honkatukia M, Reese K, Preisinger R, Tuiskula-Haavisto M, Weigend S, Roito J, Mäki-Tanila a, Vilkki J. Fishy taint in chicken eggs is associated with a substitution within a conserved motif of the FMO3 gene. Genomics. 2005 Aug;86(2):225–32. PMID: 15916878 [↩]
10. Mo F, Zheng J, Wang P, Lian L, Yi G, Xu G, Yang N. Quail FMO3 gene cloning, tissue expression profiling, polymorphism detection and association analysis with fishy taint in eggs. PLoS One. 2013 Jan;8(11):e81416. PMID: 24282592 [↩]
11. Yamazaki M, Shimizu M, Uno Y, Yamazaki H. Drug oxygenation activities mediated by liver microsomal flavin-containing monooxygenases 1 and 3 in humans, monkeys, rats, and minipigs. Biochem Pharmacol. Elsevier Inc.; 2014 May 9;1–7. PMID: 24821112 [↩]
12. Yamazaki M, Shimizu M, Uno Y, Yamazaki H. Drug oxygenation activities mediated by liver microsomal flavin-containing monooxygenases 1 and 3 in humans, monkeys, rats, and minipigs. Biochem Pharmacol. Elsevier Inc.; 2014 May 9;1–7. PMID: 24821112 [↩]