The Little Enzyme that Could

If you had to guess the most abundant protein in the world, what would you say? Maybe, given their sheer numbers, something in bacterial cells? (Bacterial cells, after all, outnumber human cells in your body by a factor of 10.) Or perhaps, given that larger organisms make up in mass what they lack in numbers, something common to all multicellular life, like an enzyme for helping cells communicate? These are reasonable guesses, but they are wrong. The most common protein in the world is found only in plants and cyanobacteria, and it goes by the name of rubisco. (If you're wondering about the pronunciation, just imagine that the Rubik's Cube people were teaming up with Nabisco to create a puzzle-themed snack wafer, and you're good to go*.)

While my tastes in music tend to the obscure and seldom-heard, my tastes in enzyme are not so refined: Rubisco is far and away my favorite one, and today I'm going to tell you why.

First off: What does rubisco even do? The full biochemical explanation is considerably more complex, but fundamentally, rubisco is responsible for snatching carbon dioxide out of the air and feeding it in to the subsequent stages of photosynthesis, a process called carbon fixation. Photosynthesis being how plants get the energy they need to survive, this is a very important job.

Unfortunately, rubisco is terrible at it. For starters, there's the speed. While most enzymes can perform tens or even hundreds of thousands of reactions per second — with one over-achiever regularly clocking in at several million per second — rubisco tops out at about ten, and sometimes trundles along as slowly as three. All the other enzymes in the photosynthesis process can whip around at breakneck paces, but not rubisco. Rubisco will not be rushed. Rubisco takes its sweet time, feeding carbon dioxide into the system in a manner that is downright leisurely.

Well, except when it tries to put oxygen in instead. You see, rubisco isn't actually that good at distinguishing between the various molecules bouncing around in our atmosphere, and sometimes it grabs an oxygen instead of a carbon dioxide by mistake. "Sometimes" as in "about 20% of the time, actually". That's bad enough, but oxygen is absolutely not what you need at this stage in the photosynthetic process, and dealing with the by-products of one of rubisco's oxygen slip-ups takes a considerable amount of energy, so much so, in fact, that if the ratio gets much worse than 20%, the plant will actually be losing energy from RuBisCO's actions instead of gaining it.

This, then, is rubisco: An enzyme with one job to do, and a critically important job at that, but an enzyme that's basically phoning in. It positively dawdles in carrying out the one thing it has to do, and still screws up so frequently that it would barely scrape out a B- for accuracy. This is why there's so much of it; there has to be or else plants would starve to death.

At this point, some of you may think I'm being unfair. After all, biological systems, especially on the molecular level, are phenomenally complex, and there are still many holes in our understanding of them. Isn't it possible that, for some deep, intractable reason, rubisco is simply the best that can be done? Maybe capturing carbon dioxide out of the air is just hard, and there aren't any possible improvements.

Well. This is where rubisco goes from being an endearingly incompetent enzyme to my favorite assemblage of amino acids ever to grace this planet. Because it turns out that rubisco is not the only way to get this done.

Meet the C4 fixation pathway**. This is an alternate method of snatching carbon dioxide out of the air that evolved independently several times, starting around 30 million years ago. It's only found in about 3% of all plant species (which together comprise about 5% of plants by biomass), but this process accounts for a full 30% of all terrestrial carbon fixation. In addition, the C4 process uses water more efficiently, giving C4 plants an advantage in times of drought. It does take a little more energy to do, but this increase is more than made up for by not having to deal with the 20% of cases where rubisco drops off an oxygen by mistake.

So how does this work? The enzymes involved don't have cutesy names, but they churn along at more typical enzyme speeds, grabbing carbon dioxide (and only carbon dioxide) out of the air and rearranging the atoms involved into a four-carbon organic acid (hence the "C4" in the name). This acid then gets shunted over to the chloroplasts where photosynthesis takes place.

But then a funny thing happens. This organic acid doesn't get fed into the photosynthetic process. Instead, it gets broken down, and reverts back to carbon dioxide. And then — and I swear this is true — rubisco comes and starts grabbing these re-constituted carbon dioxide molecules to feed into photosynthesis proper. These C4 plants have created an entirely new enzyme pathway to create a special carbon-dioxide-only mini-atmosphere just to compensate for rubisco's ineptness. Nature is full of kluges, of awkward, post-facto fixes duck taped on because there's no option for rebuilding the system from the ground up, but this one is so flagrant, so spectacularly ad-hoc and overflowing with the "eh, good enough" aesthetic that just thinking about it invariably brings a smile to my face.

Meet rubisco, an enzyme that makes up for shoddy work with the sheer quantity of its existence. Meet rubisco, an enzyme so incompetent that entire alternate pathways have evolved to paper over its flaws. Meet rubisco, my favorite enzyme in the world.

*This is, in fact, the origin of the name. It's an abbreviation for something much longer (ribulose-1,5-bisphosphate carboxylase/oxygenase, to be precise) that was introduced in 1979 in a humorous retirement speech for one of the early researchers on the enzyme, in direct parallelism with the food company. Biologists being biologists, the name stuck, and it's how everyone refers to it today.

**The 4 should technically be subscript, but I don't know how to do that using this text editor. If anyone does know, please feel free to drop me a line!