“They always call depression the blues, but for me depression is urine yellow,” says the main character in the book SharpObjects by Gillian Flynn. “Watered-down, milked-out miles of weak piss.” And while watered urine is actually a good sign. Dark yellow urine means that you have not drunk enough. But what causes that yellow color?
We read everywhere about the substance urochrome. Literally ‘urine color’. But how exactly this substance is formed was unknown until recently. Yes, it is a breakdown product of hemoglobin, the protein in our red blood cells that binds oxygen. But one step in that demolition was still a mystery. American researchers put the final piece of the puzzle together earlier this month in the magazine Nature Microbiology. They identified the enzyme in question and the intestinal bacteria that produce it.
The more official name for urochrome is urobilin, from the Greek word ‘ouron’ (urine) and the Latin ‘bilis’ (bile). The molecule has a ring structure that is very similar to that of the so-called heme group of hemoglobin. And that is no coincidence, because urobilin is a breakdown product of this.
Destroy and rebuild
Our red blood cells are constantly being broken down and regenerated. This breakdown produces the green pigment biliverdin throughout our bodies. You sometimes see this appear in old bruises. Our liver makes enzymes that convert biliverdin into bilirubin. It is orange-yellow and ends up in the small intestine via the gallbladder.
There, intestinal bacteria convert it into stercobilin, which turns our stool brown, and the colorless urobilinogen. This is partly reabsorbed into the bloodstream, where it naturally oxidizes in the kidneys to the bright yellow urobilin and ends up in the urine.
But that bacterial conversion in the intestines was still mysterious. It was clear that at least a handful of bacterial species from the class of Clostridia, but which one exactly was still unknown. And also which enzyme they use for this. A difficult search, with the five thousand types of bacteria in our intestines and their hundreds of thousands of enzymes.
The Americans who recently moved in Nature published, started that search with the known bilirubin degraders, including Clostridium ramosum. They grew these bacteria and their close relatives on culture media containing bilirubin. This way they could investigate who could break down this pigment. Nine groups of bacteria emerged from this. They subjected them to genetic analysis, looking for their mutual similarities and for differences with bacteria that do not break down bilirubin.
Closely related enzymes
This yielded 389 candidate genes, all of which were then tested by inserting them into a model bacterium (E.coli) to place. The result was a few dozen very similar genes that code for a group of closely related enzymes. The researchers gave this a collective name: bilirubin reductase. The final step was that they screened all our intestinal bacteria for this gene group in a genetic database. The result? At least 658 species of bacteria live in our intestines that can break down bilirubin.
The new enzyme group appears to be ubiquitous in healthy adults, but hardly present in newborn babies and in people with irritable bowel syndrome.
For example, intestinal flora also plays a role in depression, that was the case last year in Pharmaceuticals . Perhaps the main character was sitting there SharpObjects so not that far off after all.